Latin American Association for the Study of the Liver Practice Guidelines

array:24 ["pii" => "S1665268119317181" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31718-1" "estado" => "S300" "fechaPublicacion" => "2010-01-01" "aid" => "71380" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2010" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9 Supl 1:S8-S26" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 53 "formatos" => array:3 [ "EPUB" => 8 "HTML" => 17 "PDF" => 28 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119317193" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31719-3" "estado" => "S300" "fechaPublicacion" => "2010-01-01" "aid" => "71381" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9 Supl 1:S27-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 64 "formatos" => array:3 [ "EPUB" => 11 "HTML" => 36 "PDF" => 17 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Epidemiology of HCV infection in Latin America" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S27" "paginaFinal" => "S29" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 531 "Ancho" => 1002 "Tamanyo" => 61403 ] ] "descripcion" => array:1 [ "en" => "Prevalence of Hepatitis C infection in Latin American countries." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nahum Méndez-Sánchez, Ylse Gutiérrez-Grobe, Ramón Arturo Kobashi-Margáin" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Nahum" "apellidos" => "Méndez-Sánchez" ] 1 => array:2 [ "nombre" => "Ylse" "apellidos" => "Gutiérrez-Grobe" ] 2 => array:2 [ "nombre" => "Ramón Arturo" "apellidos" => "Kobashi-Margáin" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317193?idApp=UINPBA00004N" "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317193/v1_201906221034/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S166526811931717X" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31717-X" "estado" => "S300" "fechaPublicacion" => "2010-01-01" "aid" => "71379" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9 Supl 1:S7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 96 "formatos" => array:3 [ "EPUB" => 14 "HTML" => 65 "PDF" => 17 ] ] "en" => array:8 [ "idiomaDefecto" => true "titulo" => "The Latin American Association for the Study of the Liver in its Meeting on Diagnosis, Management and Treatment of Hepatitis C" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "S7" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nahum Méndez-Sánchez" "autores" => array:1 [ 0 => array:3 [ "preGrado" => "MD, PhD" "nombre" => "Nahum" "apellidos" => "Méndez-Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S166526811931717X?idApp=UINPBA00004N" "url" => "/16652681/00000009000000S1/v1_201906221034/S166526811931717X/v1_201906221034/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "titulo" => "Latin American Association for the Study of the Liver Practice Guidelines" "subtitulo" => "Diagnosis, management, and treatment of hepatitis C This document has been approved by the Latin American Association for the Study of the Liver (ALEH)" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S8" "paginaFinal" => "S26" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Nahum Méndez-Sánchez, Adrian Gadano, Angelo Alves de Mattos, Alejandro Soza, Augusto Marroni Claudio, Marcela Galoppo, David Kershenobich, Edna Strauss, Eduardo Fassio, Gilberto Castañeda, Guillermo Valladares, Henrique Sergio Moraes Coelho, Jorge Daruich, Miguel Garassini, Milagros Dávalos, Misael Uribe, Maribel Rodriguez-Torres, Rodrigo Zapata, Marco Arrese, Francisco Sánchez-Ávila, Margarita Dehesa, Francisco Bosques Padilla, Paulo Roberto Lerias de Almeida, Mario Pessoa, Rocío Torres-Ibarra, Francisco Hevia, Miguel Contreras, Hugo Cheinquer" "autores" => array:28 [ 0 => array:2 [ "nombre" => "Nahum" "apellidos" => "Méndez-Sánchez" ] 1 => array:2 [ "nombre" => "Adrian" "apellidos" => "Gadano" ] 2 => array:2 [ "nombre" => "Angelo" "apellidos" => "Alves de Mattos" ] 3 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Soza" ] 4 => array:2 [ "nombre" => "Augusto Marroni" "apellidos" => "Claudio" ] 5 => array:2 [ "nombre" => "Marcela" "apellidos" => "Galoppo" ] 6 => array:2 [ "nombre" => "David" "apellidos" => "Kershenobich" ] 7 => array:2 [ "nombre" => "Edna" "apellidos" => "Strauss" ] 8 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Fassio" ] 9 => array:2 [ "nombre" => "Gilberto" "apellidos" => "Castañeda" ] 10 => array:2 [ "nombre" => "Guillermo" "apellidos" => "Valladares" ] 11 => array:2 [ "nombre" => "Henrique Sergio Moraes" "apellidos" => "Coelho" ] 12 => array:2 [ "nombre" => "Jorge" "apellidos" => "Daruich" ] 13 => array:2 [ "nombre" => "Miguel" "apellidos" => "Garassini" ] 14 => array:2 [ "nombre" => "Milagros" "apellidos" => "Dávalos" ] 15 => array:2 [ "nombre" => "Misael" "apellidos" => "Uribe" ] 16 => array:2 [ "nombre" => "Maribel" "apellidos" => "Rodriguez-Torres" ] 17 => array:2 [ "nombre" => "Rodrigo" "apellidos" => "Zapata" ] 18 => array:2 [ "nombre" => "Marco" "apellidos" => "Arrese" ] 19 => array:2 [ "nombre" => "Francisco" "apellidos" => "Sánchez-Ávila" ] 20 => array:2 [ "nombre" => "Margarita" "apellidos" => "Dehesa" ] 21 => array:2 [ "nombre" => "Francisco Bosques" "apellidos" => "Padilla" ] 22 => array:2 [ "nombre" => "Paulo Roberto" "apellidos" => "Lerias de Almeida" ] 23 => array:2 [ "nombre" => "Mario" "apellidos" => "Pessoa" ] 24 => array:2 [ "nombre" => "Rocío" "apellidos" => "Torres-Ibarra" ] 25 => array:2 [ "nombre" => "Francisco" "apellidos" => "Hevia" ] 26 => array:2 [ "nombre" => "Miguel" "apellidos" => "Contreras" ] 27 => array:2 [ "nombre" => "Hugo" "apellidos" => "Cheinquer" ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Latin American Association for the Study of the Liver (ALEH)" "etiqueta" => "*" "identificador" => "aff1" ] ] ] ] "textoCompleto" => "PreambleThe following recommendations provide an approach to the establishment of guidelines for the diagnosis, management, and treatment of hepatitis C virus infection. These guidelines are based on a formal analysis and review of recently published literature around the world.Written for use especially by physicians, the recommendations suggest a range of possibilities for the epidemiology, diagnosis, and Treatment of Hepatitis C infection, but without any intention of establishing standards of care for individual patients. Although we suggest that the recommendations in these guidelines be applied appropriately according to the history of each patient, we emphasize the flexible character (individualization) of these recommendations because they are written as guidelines.IntroductionApproximately 20 years ago, Houghton, et al., discovered hepatitis C virus (HCV), which was established as the main cause of non-A non-B hepatitis. Since then, important advances have been made in the knowledge of the disease’s biological characteristics and diagnosis and also of its natural history and treatment.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>,<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The first consensus conference on hepatitis C was organized in the United States in 1997 and several meetings have since been conducted in order to present and discuss the most important advances in the evolution and management of the infection.The burden of hepatitis C is of enormous interest because of the natural course of this illness, which can lead to cirrhosis and hepatocellular carcinoma (HCC) after an asymptomatic period that may last for 25 to 30 years. It is important to know the characteristics of the infection: current findings about the progression of the disease suggest that almost 80% of patients convert to a chronic disease, at a high human and economic cost. Recent trend studies predict that HCV-related mortality will continue to increase over coming decades.<a class="elsevierStyleCrossRefs" href="#bib0015">3</a>-<a class="elsevierStyleCrossRef" href="#bib0025">5</a>The main objectives of these guidelines are to make recommendations on diagnosis, to propose preventive actions against infection, and to set up general guidelines on treatment in different risk groups. To establish the quality of evidence that supports the recommendations in these guidelines, a class and level of evidence have been assigned to each recommendation, the former reflecting benefit vs. risk and the latter the strength of the recommendation <a class="elsevierStyleCrossRef" href="#t0005">(Table 1)</a>.<a class="elsevierStyleCrossRef" href="#bib0030">6</a><elsevierMultimedia ident="t0005"></elsevierMultimedia>EpidemiologySeveral studies have estimated that approximately 180 million people around the world are infected with HCV. In Latin America, the prevalence in the general population is around 1.3%, one of the lowest in the world.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Nevertheless, the prevalence varies between countries and between regions in each country. Regional studies on this topic have estimated prevalence in the general population, and some countries have data regarding various risk groups <a class="elsevierStyleCrossRef" href="#t0010">(Table 2)</a>.<elsevierMultimedia ident="t0010"></elsevierMultimedia>In Mexico, a prevalence lower than 2% has been estimated; Chiquete et al, reported a prevalence between 0.5% and 2%,<a class="elsevierStyleCrossRef" href="#bib0040">8</a> and Valdespino et al, found a general prevalence of 1.6%.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> In Brazil, several studies carried out in the general population in different regions of that country have estimated a mean prevalence of 1.32% of HCV.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> General population studies have not been carried out in the Dominican Republic, but data from the Public Health Department estimate a prevalence of 1.5%.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In Puerto Rico, studies carried out in the general population have estimated a prevalence of 2.4%; Perez, et al., determined that the seroprevalence is similar to that found in the US general population, but concluded that further research is needed in that region.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>In the Dominican Republic, several studies in risk groups determined a prevalence of 2% in men who have sex with men and a study carried out in the sugarcane fields of the province of Barahona determined a prevalence of 5.3% in this group of working women.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> In Costa Rica, studies carried out among voluntary blood donors between 1992 and 2008 estimated a prevalence of 0.3% to 2%,<a class="elsevierStyleCrossRefs" href="#bib0070">14</a>-<a class="elsevierStyleCrossRef" href="#bib0080">16</a> and in Peru, the prevalence among blood donors has been reported to be 0.8% to 1.2%.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> In Chile, studies carried out in blood donors have estimated a prevalence of around 0.3%. However, the National Health Survey showed a prevalence of 0.12% and studies carried out in Santiago revealed a prevalence of 1.15%.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>Although no large-scale population studies have been carried out in Argentina, several studies according to the National Consensus on hepatitis C estimate a prevalence of about 2.1%.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>Recommendations<ul class="elsevierStyleList" id="li0025"><li class="elsevierStyleListItem" id="list0170">1.Large-scale population studies must be carried out in every Latin American countries to gather better and complete data about the prevalence of hepatitis C in the region (Class I, Level C).</li></ul>Transmission RoutesTo assist in creating new methods of control and therapy, it is mandatory to identify the different means of transmission of HCV. HCV can be transmitted by several parenteral routes, of which blood transfusion and intravenous drug use (IVD) are the most common. In developed countries, the main transmission route is the use of intravenous drugs, but in Latin America, several studies show that the main transmission route continues to be transfusion of blood and its derivatives. The frequency of infection by this route has diminished because of the establishment in around 1992 of screening measures in blood banks. However, although current methods for the selection of blood donors and the screening tests are highly developed and the risk of transmission is far lower than 15 years ago, the risk remains. At the same time, intravenous and intranasal drug abuse is increasing in Latin America, making it the second most important route of transmission. According to the current epidemiological model, it is possible that in a few years it will be the main form of transmission, similar to the United States and Europe.<a class="elsevierStyleCrossRefs" href="#bib0030">6</a>,<a class="elsevierStyleCrossRef" href="#bib0100">20</a> The use of contaminated needles and paraphernalia is one of the most effective modes of transmission of HCV. Several studies have shown that 65% of infected intravenous drugs users (IVDU) acquire the virus during the first year of drug abuse.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Other potential means of transmission include contact with one or more infected sexual partners, although the prevalence is higher in persons with several partners than in monogamous couples. Even though it is practical to advise HCV carriers that they should inform their partners of their condition, they should be equally informed that the risk of catching the disease is low, as only 1% to 5% of monogamous couples become HCV positive when one of the partners is a carrier. However, the transmission rate increases in persons with multiple sexual partners and persons who have sexual intercourse with prostitutes, anal intercourse, traumatic relations, or intercourse during menses or with inadequate lubrication. Despite the low risk, the use of prophylactic condoms is recommended to nonmonogamous couples. No limitations are recommended on the daily activities of persons with HCV except in the use of razor blades and tooth brushes that should not be shared with other people.By contrast, vertical transmission occurs in approximately 5% of the children born from an infected mother, with the risk further increased if the mother is also infected with human immunodeficiency virus (HIV). Nevertheless, there is currently not enough information to recommend a managed form of delivery.<a class="elsevierStyleCrossRefs" href="#bib0110">22</a>-<a class="elsevierStyleCrossRef" href="#bib0120">24</a>Hemodialysis patients have an increased risk of acquiring the infection. The prevalence in hemodialysis patients in Latin America is reported as ranging from 6.7% in Mexico to 71% in Venezuela.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>,<a class="elsevierStyleCrossRef" href="#bib0130">26</a> For healthcare workers, the main risk is through accidental contact with contaminated needles and percutaneous injuries, with the risk of infection being 1.8%; a lower prevalence occurs through contact with exposed mucosa.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> Other less common forms of transmission are tattooing and body piercing; because of this, screening is recommended in this high-risk population and in IVDU.Recommendations<ul class="elsevierStyleList" id="li0030"><li class="elsevierStyleListItem" id="list0175">1.Blood donors who have a positive result during screening should be informed in order to prevent transmission (Class I, Level C).</li><li class="elsevierStyleListItem" id="list0180">2.Persons infected with HCV should be counseled with the intention of avoiding transmission to others (Class I, Level C).</li><li class="elsevierStyleListItem" id="list0185">3.Persons infected with HCV should be counseled with the intention of avoiding donation of blood, organs, other tissues, and semen (Class I, Level C).</li><li class="elsevierStyleListItem" id="list0190">4.Viral Hepatitis screening should be mandatory in every blood donor. (Class I, Level A).</li></ul>DiagnosisBecause patients with chronic infection generally are asymptomatic, to date the best way to diagnose the infection is screening persons with risk factors and a history of exposure to the virus, in addition to counseling.Diagnostic tests are classified into serological tests, which identify specific anti-HCV IgG, and molecular tests that identify viral nucleic acid. The initial evaluation is through third-generation immunoenzymatic techniques that identify antibodies against different epitopes of HCV and that have sensitivity and specificity of 97% and 99%, respectively. Also available is the recombinant immunoblot assay (RIBA), which was originally developed as a more specific test to confirm results from ELISA. However, this is about to fall into disuse because of the usefulness of ELISA. Although HCV antibodies remain detectable lifelong in immunocompetent patients with chronic infection, in patients that recover spontaneously, antibodies tend to disappear within 18 to 20 years. Thus, detection of antibodies indicates contact with the virus only and does not discriminate between acute, chronic, or resolved infection. Interestingly, confirmation of an active HCV infection is performed by demonstrating the presence of HCV-RNA through quantitative detection by RNA amplification methods such as polymerase chain reaction (PCR) or transcription mediated amplification (TMA).<a class="elsevierStyleCrossRef" href="#bib0030">6</a> These assays must have a sensitivity of at least 50 IU/mL. Viral RNA can be detected 2 weeks post infection while antibodies are detectable 8 to 12 weeks after contact; therefore, adequate interpretation is required within the different contexts of the test results.Because of the great genomic variability of HCV, of which six types and more than 90 subtypes are known, genotype determination is useful in epidemiological studies and to identify and predict the possibility of resistance to treatment and the appropriate duration for patient treatment and follow-up.Recommendations<ul class="elsevierStyleList" id="li0035"><li class="elsevierStyleListItem" id="list0195">1.Screening in the general population is not recommended (Class I, Level C).</li><li class="elsevierStyleListItem" id="list0200">2.Determination of anti-HCV antibodies is the test of choice for the initial diagnosis in patients with suspected acute or chronic HCV infection (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0205">3.Anti-HCV determination should be done in patients with the following risk factors (Class IIa, Level B):<ul class="elsevierStyleList" id="li0040"><li class="elsevierStyleListItem" id="list0210">a)People who received a blood transfusion before 1992.</li><li class="elsevierStyleListItem" id="list0215">b)Intravenous drug users.</li><li class="elsevierStyleListItem" id="list0220">c)Patients in hemodialysis.</li><li class="elsevierStyleListItem" id="list0225">d)Patients with elevated aminotransferases.</li><li class="elsevierStyleListItem" id="list0230">e)Healthcare workers exposed to infected blood.</li><li class="elsevierStyleListItem" id="list0235">f)Patients with hemophilia who received clotting factor concentrates before 1987.</li><li class="elsevierStyleListItem" id="list0240">g)Children born to mothers infected with HCV.</li><li class="elsevierStyleListItem" id="list0245">h)Sexual partners of hepatitis C patients.</li><li class="elsevierStyleListItem" id="list0250">i)HIV infected patients.</li></ul></li><li class="elsevierStyleListItem" id="list0255">4.Viral RNA analysis should be done in:<ul class="elsevierStyleList" id="li0045"><li class="elsevierStyleListItem" id="list0260">a)Patients positive for anti-HCV antibodies (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0265">b)Patients in whom antiviral treatment is considered (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0270">c)Immunosuppressed patients with unexplained chronic elevation of aminotransferase levels. (Class I, Level B).</li></ul></li></ul>Utility of Liver Biopsy in Chronic InfectionLiver biopsy is a procedure indicated in a broad spectrum of diseases. The basic requirements for its use are the benefits that it will bring to the patient, as well as the impossibility of obtaining the same detailed information with any other procedure. Possible benefits include identification of liver status, identification of useful characteristics at the time of treatment decisions, or monitoring of the advance of fibrosis or cirrhosis that needs surveillance for HCC. However, the use of this diagnostic procedure in chronic HCV has been questioned in recent years. In addition, the act of soliciting a biopsy can be a challenge because of its invasiveness and because patients correlate the procedure with malignancy. However, advances in surgical techniques and the control of hemorrhage in the second half of last century have diminished complications during this procedure. Liver biopsy continues to be the preferred method to allow evaluation of the grade and stage of hepatic lesions. Patients with confirmed serology for Hepatitis C and clinical and/or laboratorial data for other associated diseases, as auto-immune or metabolic disorders, certainly deserve liver biopsy for differential diagnosisAlthough liver biopsy has been established as the “gold standard” in the diagnosis of chronic hepatitis C, it is not without contraindications and complications. The main contraindications to biopsy are alterations in coagulation and tense ascites. A prolonged prothrombin time and a low platelet count are major risk factors for bleeding. In addition, because of the possible subjectivity of histological description and interpretation, numeric systems have been proposed to make classification of necrosis, inflammation, and fibrosis less subjective <a class="elsevierStyleCrossRef" href="#t0015">(Table 3)</a>.<elsevierMultimedia ident="t0015"></elsevierMultimedia>Recommendations<ul class="elsevierStyleList" id="li0050"><li class="elsevierStyleListItem" id="list0275">1.Liver biopsy is essential in those patients with hepatitis C in whom more information is required about the stage of fibrosis and/or grade of peri-portal or lobular inflammation, for prognostic purposes (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0280">2.For patients with presumed associated conditions, as auto-immune or metabolic disorders, a liver biopsy can effectively make a differential diagnosis (Class I, Level B).</li></ul>Use of Noninvasive Methods to Evaluate The Stage of Liver FibrosisAlthough liver biopsy is considered the “gold standard” for the diagnosis of hepatic fibrosis, because of its complications and technical difficulty, noninvasive methods have been developed for the evaluation of fibrosis. However, such methods are most effective for the early stages of disease with little fibrosis or cirrhosis, leaving the intermediate stages without a reliable diagnostic method. One of the new methods is transient elastography; this method has not fulfilled all the criteria necessary to replace hepatic biopsy but has proven its efficacy in the diagnosis of fibrosis extension when combined with other noninvasive methods.Recently, noninvasive methods such as transient elastography and FibroTest ® have been studied in patients with persistently normal alanine transaminase (ALT) levels. The results show that transient elastography might be very useful in the selection of patients with significant fibrosis for antiviral therapy, and eventually remove the need for taking a liver biopsy.Indications and Contraindications for the Treatment of Hcv InfectionEvidence shows that 55% to 85% of HCV-infected patients will remain infected through their lifetime. The risk of developing cirrhosis rises from 5% to 25% over a period of 30 years.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> Prior to treatment, it is necessary to know the stage of liver disease, to determine the presence of compensated or decompensated cirrhosis or portal hypertension, and to know factors such as age, comorbidities, extrahepatic manifestations such as cryoglobulinemia and glomerulonephritis, and quality of life.Consensus indicates that treatment should be with a combination of pegylated interferon and ribavirin. Medical treatment is indicated in patients who are anti-HCV positive and HCV-RNA positive and in whom histological evidence indicates chronic hepatitis.The goal of treatment is to prevent complications and death related to HCV infection. Because of the chronic evolution of the disease, the response is determined by several biochemical, virological, or histological variables including normalization of ALT levels, absence of viral RNA on PCR, or improvement of at least two points on the scale of necroinflammation or fibrosis scores.Current recommendations to treat chronic HCV-infected patients have been suggested from randomized clinical trials. Characteristics of patients in whom therapy is accepted are shown in <a class="elsevierStyleCrossRef" href="#t0020">Table 4</a>, and characteristics of patients in whom therapy is contraindicated are shown in <a class="elsevierStyleCrossRef" href="#t0025">Table 5</a>.<elsevierMultimedia ident="t0020"></elsevierMultimedia><elsevierMultimedia ident="t0025"></elsevierMultimedia>Patients with HCV genotype 2 or 3 may be treated in any stage of the disease because of the elevated frequency of sustained virological response (SVR) in those groups.Recommendations<ul class="elsevierStyleList" id="li0055"><li class="elsevierStyleListItem" id="list0285">1.The decision to establish therapy for any patient has to be individualized, with awareness of the severity of liver damage, the probability of response to treatment, the potential for severe adverse effects, and the presence of comorbidities (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0290">2.The ideal patients to treat are those with chronic hepatitis C, with genotype 2 and 3 and low viral load and those who have Child A liver cirrhosis associated with > 75,000 platelets/ml and hemoglobin > 12 g/dL (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0295">3.Combined treatment with pegylated interferon and ribavirin is contraindicated in patients with:<ul class="elsevierStyleList" id="li0060"><li class="elsevierStyleListItem" id="list0300">a)Decompensated psychiatric disease.</li><li class="elsevierStyleListItem" id="list0305">b)Decompensated diabetes mellitus.</li><li class="elsevierStyleListItem" id="list0310">c)Decompensated arterial hypertension.</li><li class="elsevierStyleListItem" id="list0315">d)Decompensated hemoglobinopathy.</li><li class="elsevierStyleListItem" id="list0320">e)Autoimmune disease with the exception of treated autoimmune thyroid disease.</li><li class="elsevierStyleListItem" id="list0325">f)Immunosuppressive treatment.</li><li class="elsevierStyleListItem" id="list0330">g)Thrombocytopenia < 50,000 platelets/mL.</li><li class="elsevierStyleListItem" id="list0335">h)Neutropenia < 750 cells/mL.</li><li class="elsevierStyleListItem" id="list0340">i)Hemoglobin < 12g/dL. (Class II, Level A).</li></ul></li></ul>Predictive Factors for the Response to TreatmentDuring treatment, several types of virological response may occur, the most important of which is the SVR, which is defined as the absence of detectable serum viral RNA by PCR assay for 24 weeks after suspension of treatment. Knowledge prior to treatment of the factors predictive of treatment response is useful to predict SVR. The combination of pegylated interferon with ribavirin has an SVR in 50% to 80% of patients. However, this rate is still low considering the adverse effects, costs, and duration of treatment.It is possible to predict SVR before the beginning of treatment if several characteristics of the virus or of the host are known, such as viral genotype (1 vs. non-1), pretreatment viral load, fibrosis stage, gamma-glutamyl transpeptidase (GGTP), age, race, weight, and insulin resistance. Other predictive factors might be identified after initiating treatment, such as the rapid viral response (RVR; viral RNA not detectable by the fourth week of treatment) and the early viral response (EVR; a reduction of at least 2 log in viral load by the 12th week or a negative HCV-PCR).<a class="elsevierStyleCrossRefs" href="#bib0145">29</a>-<a class="elsevierStyleCrossRef" href="#bib0160">32</a> In patients with HCV genotype 1, the rate of response to treatment based on pegylated interferon and ribavirin is 40%, whereas in patients with genotype 2 or 3 it is around 80%.Another important factor is coinfection with other viruses, because a lower rate of response to treatment has been observed in patients coinfected with hepatitis B virus (HBV). In HIV-coinfected patients, development of fibrosis is faster and the progression to liver failure and hepatocellular carcinoma occurs earlier, but response rates are similar to those of patients without HIV coinfection.Patients with hepatitis C and cirrhosis have lower rates of sustained response. Even when cirrhosis is absent, the probability of response to treatment diminishes as the stage of fibrosis increases. In addition, treatment compliance has been demonstrated to be a fundamental factor in treatment effectiveness, so that every effort must be made to ensure the patient maintains the dose and duration of treatment.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>However, and despite the inadequate predictive factors for response, it is possible that in the near future, new techniques will be developed. These could include the identification of individual genetic polymorphisms such as the one found near the IL-28B gene encoding interferon γ3 that is associated with an approximately twofold change in response to treatment<a class="elsevierStyleCrossRef" href="#bib0170">34</a> and profiles of protein expression that will open up a new world of possibilities to better identify good and bad responders to HCV therapy. It is considered that complete remission of the infection has occurred when there is no detectable viral load of HCV 6 months after the completion of a course of treatment.Recommendations<ul class="elsevierStyleList" id="li0065"><li class="elsevierStyleListItem" id="list0345">1.The major pre-treatment predictive factors for treatment response are viral load, viral genotype, and fibrosis stage. Recently RVR has been appointed as the most important predictive factor of SVR. (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0350">2.The principal negative predictive factor is a detectable viral load or a reduction of less than 2 logs by the 12th week of treatment (Class I, Level A).</li></ul>Hepatitis C Treatment in Naïve PatientsThe selection of candidate patients to receive treatment should take into consideration several factors including: the probability of response, the likelihood for adverse effects, cost, and effectiveness of treatment.The aim of therapy is to prevent long-term complications and death caused by this disease. In the short term, SVR, normalization of ALT levels (if abnormal), and histological improvement are more important. This is achieved with viral eradication, which is defined as undetectable viral RNA 6 months after finishing therapy (SVR). All HCV-infected people are potentially treatable unless contraindications exist.The therapeutic regimens depend on the type of interferon and the viral genotype. It has been confirmed by several studies that treatment should include a combination of pegylated interferon plus ribavirin because of its greater efficacy compared with monotherapy of interferon and with the combination of standard interferon plus ribavirin. A meta-analysis recently published comparing both types of pegylated interferons showed a trend toward higher SVR rates with peginterferon alpha 2a (47%) compared with peginterferon alpha 2b (41%).<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Treatment must also be strictly supervised by experts in order to document its effectiveness and safety.Patients with HCV genotype 1 are considered difficult to cure because the SVR rate is considerably lower in this group of patients than in patients with non-1 genotype HCV. For this reason, several studies have been carried out that demonstrate that treatment with pegylated interferon and ribavirin at higher doses for a period of 48 weeks may obtain a greater rate of SVR.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>,<a class="elsevierStyleCrossRef" href="#bib0155">31</a>For patients with HCV genotype 2 or 3, it has been established that treatment should be for 24 weeks with a combination of pegylated interferon plus ribavirin, which shows an effectiveness around 80%–90%.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> However, patients with genotypes 2 or 3 who do not show a RVR have a rather low SVR. In this setting, an extension of treatment duration to 36–48 weeks might be considered.Recommendations<ul class="elsevierStyleList" id="li0070"><li class="elsevierStyleListItem" id="list0355">1.Virological response to treatment must be monitored at the 4th, 12th, and 24th weeks of treatment and at the 24th week after treatment is finished, always with the same method (Class II, Level A).</li><li class="elsevierStyleListItem" id="list0360">2.Treatment of patients with HCV genotype 1 must be for 48 weeks with pegylated interferon alpha 2b 1.5 mg/kg/week s.c. or pegylated interferon alpha 2a 180 mg/kg/week s.c. combined with weight dosed ribavirin 800–1400 mg/day (weight-based dose)<a class="elsevierStyleCrossRef" href="#t0030">(Table 6)</a>(Class I, Level A).<elsevierMultimedia ident="t0030"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="list0365">3.Patients with HCV genotype 1 with factors predictive of good response and RVR may be treated for 24 weeks (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0370">4.In slow-responder patients, a treatment for 72 weeks should be considered (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0375">5.In patients who do not achieve EVR and those that present with detectable viral RNA at 24 weeks, treatment ought to be suspended (Class II, Level A).</li><li class="elsevierStyleListItem" id="list0380">6.Patients with HCV genotype 2 or 3 must be treated with pegylated interferon plus ribavirin for 24 weeks (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0385">7.Treatment of patients with HCV genotype 2 or 3 with factors predictive of a good response may be shortened to 16 weeks (Class II, Level A).</li><li class="elsevierStyleListItem" id="list0390">8.Treatment of patients with HCV genotype 2 or 3 with bad or slow virological response may be prolonged to 36–48 weeks (Class II, Level A).</li></ul>Approach and Management of Patients With Normal Levels of TransaminasesApproximately 30% of patients with chronic hepatitis C have persistently normal ALT (PNALT) values. Most of these patients have mild or moderate inflammation and absent or mild fibrosis, which can progress over time determining cirrhosis or hepatocellular carcinoma might be found.<a class="elsevierStyleCrossRefs" href="#bib0185">37</a>-<a class="elsevierStyleCrossRef" href="#bib0215">43</a>AST and ALT elevations normally act as important markers of liver injury. However, the definition of “normal values” is currently subjective because reference ranges vary between laboratories, with values above 40 U/L considered high normal levels. There are also differences between males and females: recent data show that in the healthy population the upper level of normal ALT should be around 30 U/L for men and around 19 U/L for women. Application of these limits would improve the sensitivity of the test for detecting patients with asymptomatic disease, although the specificity would diminish. The definition of PNALT in patients with chronic hepatitis C varies in the literature, but most authors define it as ALT measurements lower than 40 U/L on two or three different occasions separated by at least 1 month in a period of 6 months. Most PNALT patients are women; nearly 50% have a genotype 1 virus and viral RNA titers are significantly lower than in patients with elevated ALT. Although hepatic damage is generally mild and stable over time in patients with PNALT and they maintain a good prognosis, almost 20% to 30% of these patients progress to fibrosis, which is why they have recently been considered ade-quate candidates for antiviral therapy.Recommendations<ul class="elsevierStyleList" id="li0075"><li class="elsevierStyleListItem" id="list0395">1.The indications for treatment must be evaluated independently of ALT activity (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0400">2.Treatment protocols in patients with PNALT must be the same as that used in patients with elevated ALT. Likewise, the SVR to combined treatment is similar to that observed in patients with elevated ALT (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0405">3.As in other patients, treatment must be individualized and adverse effects, comorbidities, likelihood for therapy response, the viral genotype, and the severity of illness assessed by liver biopsy must be considered before treatment commences (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0410">4.In PNALT patients in which antiviral treatment is not initiated due to minimal liver disease, ALT levels must be monitored every 6 to 12 months and the possibility of taking serial liver biopsies to evaluate the progression of the disease should be offered to reconsider antiviral therapy (Class I, Level B).</li></ul>Treatment in Cirrhotic PatientsThe main objectives of treatment in cirrhotic patients are to prevent disease complications, allow regression of fibrosis, and avoid reinfection of the graft in those patients who will receive a liver transplantation.When SVR is evaluated in cirrhotic patients, especially in those with decompensated disease, we observe that it is lower than in those patients with chronic hepatitis without cirrhosis. It has also been described that cirrhotic patients present a higher probability of having treatment complications.Of patients with Child A cirrhosis, it is reported that almost 30% to 40% have SVR; and patients who do not have SVR have a higher probability of developing HCC and a higher mortality rate.<a class="elsevierStyleCrossRef" href="#bib0220">44</a>With respect to treatment benefits, from an evaluation of studies carried out in patients with cirrhosis, we conclude that the SVR is inferior and that the evidence level for treatment success is lower for decompensated cirrhotic patients because of the small response and increased probability of developing complications.Treatment with pegylated interferon plus ribavirin is clearly indicated in patients with compensated cirrhosis, with the condition that their levels of white cells and platelets allow them to tolerate the decrease induced by the treatment. The therapy may be contraindicated in advanced cirrhotic patients with Child B and C class liver disease, due to possibility of decompensation and death.Recommendations<ul class="elsevierStyleList" id="li0080"><li class="elsevierStyleListItem" id="list0415">1.Patients with compensated Child A cirrhosis must be referred for evaluation and must receive the usual treatment (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0420">2.Patients with Child B cirrhosis awaiting transplantation must be treated if the virus is genotype 2; patients with Child B and C liver disease should be treated after compensation (Class II, Level B).</li><li class="elsevierStyleListItem" id="list0425">3.Patients with decompensated Child B and C liver disease should be referred to a transplantation unit for evaluation (Class I, level A).</li></ul>Treatment in Posttransplantation PatientsLiver transplantation offers an effective treatment that significantly reduces morbidity and mortality among these patients. However, hepatic graft reinfection is universal in posttransplantation patients because of the advanced liver disease related to HCV. Reinfection is almost inevitable in patients with measurable viral RNA subjected to liver transplantation.<a class="elsevierStyleCrossRefs" href="#bib0225">45</a>-<a class="elsevierStyleCrossRef" href="#bib0245">49</a> The natural history of hepatitis C is more aggressive after liver transplantation than in immunocompetent patients. Graft cirrhosis has been reported in almost 30% of patients five years after liver transplantation and the survival rate is significantly lower than that in HCV-negative patients.The aim of antiviral therapy prior to transplantation is to reach an SVR at the moment of transplantation and clearance of viral RNA to prevent recurrence and stop disease progression.<a class="elsevierStyleCrossRefs" href="#bib0250">50</a>-<a class="elsevierStyleCrossRef" href="#bib0260">52</a>A preventive strategy seems attractive because treatment is begun while viral levels remain low and before the graft is damaged and thus would be expected to reach higher SVR rates. Nevertheless, in practice only 40% to 60% of patients are candidates to receive treatment in view of the fact that these patients receive high doses of immunosuppression with its consequent pancytopenia, mild renal dysfunction, and the presence of additional medical conditions during the early posttransplantation phase.<a class="elsevierStyleCrossRefs" href="#bib0030">6</a>,<a class="elsevierStyleCrossRef" href="#bib0235">47</a>,<a class="elsevierStyleCrossRefs" href="#bib0240">48</a>,<a class="elsevierStyleCrossRefs" href="#bib0265">53</a>-<a class="elsevierStyleCrossRef" href="#bib0280">56</a> Monotherapy with interferon or peginterferon is not recommended because of low rates of SVR.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> Peginterferon combined with ribavirin gives higher response rates, but is not well tolerated in patients in the early posttransplantation phase, so the doses need to be reduced in the majority of cases.Recommendations<ul class="elsevierStyleList" id="li0085"><li class="elsevierStyleListItem" id="list0430">1.Treatment of HCV in patients who receive a liver transplantation is indicated only in candidate patients with adequate supervision of therapy administration and of adverse effects (Class IIA, Level A).</li><li class="elsevierStyleListItem" id="list0435">2.The therapeutic regime of choice in posttransplantation patients should be peginterferon with ribavirin (Class IIa, Level B).</li><li class="elsevierStyleListItem" id="list0440">3.Posttransplantation patients should receive erythropoietin and granulocyte growth factor so that the ribavirin dosage does not need to be reduced (Class I, Level B).</li></ul>Treatment in Nonresponders and RelapsersIt is considered that almost 60% of patients treated with standard interferon and ribavirin do not respond to treatment. The numbers are even more concerning for the genotype 1 subgroup, as 60% to 75% of these patients will not respond to therapy, while in the genotype 2 and 3 group of patients, almost 30% to 40% will not respond. The response to therapy with pegylated interferon plus ribavirin varies according to the viral genotype: it has been found that patients with genotype 1a have an SVR rate of 42% to 52%,<a class="elsevierStyleCrossRef" href="#bib0150">30</a> whereas patients with genotype 2 or 3 have an SVR rate of 76% to 84%. If the viral load does not diminish by 2 logs by the 12th week of treatment, the patient is considered a nonresponder. If the viral load is undetectable at the end of treatment but reappears 6–12 months after the treatment, the patient is considered a relapser.In nonresponding patients, retreatment with the same therapeutic regime reaches an SVR of less than 5%, so is not recommended. Furthermore, modification of therapy with alternative interferons does not demonstrate sufficient evidence of success.Although it is probable that patients who relapse will respond to the same treatment as given the first time, it is very probable that they will relapse again. In these patients that relapse, the following therapeutic regimes have been proven effective: pegylated interferon alpha-2b 1.5 mg/kg/week plus ribavirin 800 mg daily, and pegylated interferon 1 mg/kg/week plus ribavirin 1,000 to 2,000 mg a day. However, the SVR is 50% with the former therapy and 32% with the latter.<a class="elsevierStyleCrossRef" href="#bib0290">58</a>In a study carried out by Reddy, et al., patients received pegylated interferon alpha 2a 180 pg per week plus ribavirin 1,000 to 2,000 mg a day for 48 weeks; higher relapse rates were seen in patients over 50 years (SVR 39%) than in younger patients (SVR 52%).<a class="elsevierStyleCrossRef" href="#bib0295">59</a> Everson and colleagues also described that another predictive factor for a poor prognosis is advanced fibrosis level and cirrhosis. In non responder patients re-treated with pegylated interferon alpha 2a the authors found that a significant reduction in SVR rates occurred as disease severity increased.<a class="elsevierStyleCrossRef" href="#bib0300">60</a>Recommendations<ul class="elsevierStyleList" id="li0090"><li class="elsevierStyleListItem" id="list0445">1.Retreatment with pegylated interferon plus ribavirin in nonresponders and relapsers should be individualized. Treatment should be stopped if HCV RNA is detectable at 12 weeks at any level. (Class II, Level B).</li><li class="elsevierStyleListItem" id="list0450">2.Retreatment with pegylated interferon plus ribavirin in nonresponders and relapsers to a previous course of standard interferon plus ribavirin or interferon monotherapy may be intended. (Class II, Level B).</li><li class="elsevierStyleListItem" id="list0455">3.The next patients are considerate good candidates for re treatment:<ul class="elsevierStyleList" id="li0095"><li class="elsevierStyleListItem" id="list0460">°Prior relapse (vs non-response)</li><li class="elsevierStyleListItem" id="list0465">°Prior non-adherence (if correctable)</li><li class="elsevierStyleListItem" id="list0470">°Previous monotherapy (vs IFN/RBV)</li><li class="elsevierStyleListItem" id="list0475">°No cirrhosis</li><li class="elsevierStyleListItem" id="list0480">°Genotype 2–3 with low viral load (Class II, Level B).</li></ul></li><li class="elsevierStyleListItem" id="list0485">4.These patients should be monitored frequently and the therapeutic trial should be intended for at least 12 weeks. (Class II, Level B).</li></ul>Management of Hcv Infection in Pregnant WomenThe prevalence of anti-HCV antibodies in pregnant women is similar to that in the general population, and tends to increase in pregnant women with significant risk factors such as IVDU and HIV coinfection. In the absence of cirrhosis and portal hypertension, pregnant women infected with HCV do not have obstetric complications, although there are reports of prematurity, low birth weight, and microcephaly. It is infrequent that women with cirrhosis become pregnant. However, if they do, special care is required because of the possibility of decompensation and worsening of the portal hypertension secondary to the increase in abdominal pressure and in the plasma volume and the secondary coagulopathy that may induce severe hemorrhage during delivery.<a class="elsevierStyleCrossRefs" href="#bib0300">61</a>-<a class="elsevierStyleCrossRef" href="#bib0315">63</a><a class="elsevierStyleCrossRef" href="#t0035">Table 7</a> shows the indications for screening in pregnant women.<elsevierMultimedia ident="t0035"></elsevierMultimedia>Several studies have shown no evidence that the type of birth influences perinatal transmission. Likewise, several studies performed on breast-feeding indicate that even though small quantities of HCV are found in breast milk and colostrum, these levels are not sufficient to transmit infection because the virus may be inactivated by gastric juices and the immunological compounds of breast milk.<a class="elsevierStyleCrossRefs" href="#bib0320">64</a>-<a class="elsevierStyleCrossRef" href="#bib0330">66</a>Treatment based on pegylated interferon and ribavirin is contraindicated because of the elevated teratogenicity of the ribavirin and the neurotoxic effect of interferon. Antiviral treatment is not recommended during pregnancy.Recommendations<ul class="elsevierStyleList" id="li0100"><li class="elsevierStyleListItem" id="list0490">1.Every HCV-infected patient must be counseled to avoid alcohol and to prevent hepatotoxic drug use including medicinal herbs (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0495">2.Patients who have not been immunized against hepatitis A and B must be vaccinated against these viruses (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0500">3.Pregnant women with premature membrane rupture over 6 hours or vaginal rupture may receive treatment in order to avoid vertical transmission (Class II, Level B).</li></ul>Management of Hcv Infection in ChildrenThe global prevalence of hepatitis C among children is very low, about 1%, so little is known about this disease. The risk groups correspond principally to children with hematological disorders who received transfusions before 1992, and vertical transmission represents one of the most important routes of transmission. Screening of anti-HCV in children of HCV-infected mothers must be performed after 18 months of age because of the high rate of antibodies transmitted from the mother within the first months after birth. However, if an early diagnosis of HCV infection is desired, testing for serum HCV RNA may be performed at 1–2 months of age.Most infected children, regardless of the age at which infection was acquired, become chronically ill. Spontaneous resolution in children seems to be infrequent, although the highest frequency occurs in patients infected with genotype 3.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>,<a class="elsevierStyleCrossRefs" href="#bib0335">67</a>-<a class="elsevierStyleCrossRef" href="#bib0350">70</a> In children, the disease is classically asymptomatic and characterized by a benign course for approximately two decades. Advanced liver disease is extremely rare among pediatric patients. Because of the slow progress of the disease, children are ideal patients for treatment with the goals of viral clearance, regression or retardation of fibrosis onset, prevention of chronic disease and the development of HCC, and improvement of quality of life. Treatment is considered for patients aged 3–18 years, and studies performed so far support the efficacy of combined treatment with pegylated interferon alpha 2a at doses of 100 mg/m2/week or pegylated interferon alpha 2b at doses of 60 mg/m2/week or 1.5 mg/kg/week plus ribavirin at doses of 15 mg/kg/day for 48 weeks.Recommendations<ul class="elsevierStyleList" id="li0105"><li class="elsevierStyleListItem" id="list0505">1.Diagnosis of HCV in children is performed by the same methods as in adults (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0510">2.Treatment can be started from the age of 3 years with the same indications as in adults (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0515">3.Screening for anti-HCV must be considered at 18 months in children born to HCV-infected mothers (Class I, Level B). Testing for HCV RNA may be performed at 1–2 months of age if an earlier diagnosis is desired.</li><li class="elsevierStyleListItem" id="list0520">4.Treatment is based on combined pegylated interferon alpha 2a at doses of 100 mg/m2/week or alpha 2b at doses of 60 mg/m2/week or 1–1.5 mg/kg/week plus ribavirin at doses of 15 mg/kg/day for 48 weeks (Class I, Level B).</li></ul>Treatment of HCV-Infected Patients with Kidney DiseasePatients with kidney disease may be infected by HCV through hemodialysis (due to contaminated blood, the absence or inadequate disinfection of medical equipment, or sharing vials of heparin)It has been demonstrated that in HCV-infected patients with kidney dysfunction under treatment with hemodialysis, mortality increases because of progression of the liver damage (cirrhosis and HCC). In addition, individual and transplanted organ survival rates decrease after kidney transplantation.By contrast, it has been noted that levels of ALT in individuals with chronic kidney failure are only slightly elevated or even normal despite the advanced hepatic damage. Thus, hepatic biopsy is recommended in these patients in order to determine the stage of the hepatic lesion following the same guidelines for the procedure in patients without renal dysfunction. Even though patients with renal disease have a major platelet dysfunction that may favor hemorrhagic states, complications are rarely reported in hemodialyzed patients who undergo hepatic biopsy.Anti-HCV measurement and HCV-RNA quantification should be completed in all patients before initiation of hemodialysis and before and after kidney transplantation. Likewise, screening must be performed in hemodialyzed patients who present with any spontaneous or unexplained liver damage and in people who suffer a nosocomial exposure to HCV.The suggested treatment continues to be peginterferon plus ribavirin, even in hemodialyzed patients. However, the grade of kidney dysfunction must be taken into account because both drugs are filtered by the kidney. Ribavirin increases the risk of hemolytic anemia and cannot be removed by hemodialysis, so a lower dose and caution in its administration or even avoiding the administration are recommended when the creatinine clearance is < 50 mL/min <a class="elsevierStyleCrossRef" href="#t0040">(Table 8)</a>.<elsevierMultimedia ident="t0040"></elsevierMultimedia>Hepatitis C virus (HCV) infection is a risk factor of a variety of extrahepatic diseases, such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN), which is the most common glomerulonephritis. In these cases, treatment is indicated in order to eliminate the antigen-stimulating process, although therapy must be individualized, as ribavirin is contraindicated in individuals with creatinine clearance < 50 mL/min, pegylated interferon is poorly tolerated in end stage renal disease and is contraindicated in renal allograft recipients. In addition, when the autoimmune is process is very active, it must be controlled first with the adequate inmunosuppresive therapy, and once the patient is stabilized, antiviral therapy may be considered.Recommendations<ul class="elsevierStyleList" id="li0110"><li class="elsevierStyleListItem" id="list0525">1.HCV screening must be carried out in all renal patients under hemodialysis treatment who are considered for kidney transplantation (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0530">2.A liver biopsy must be considered in all patients on hemodialysis who present with any spontaneous or unexplainable liver damage (Class IIa, Level C).</li><li class="elsevierStyleListItem" id="list0535">3.The dose and type of treatment need to be based on the stage of renal function measured by the glomerular filtration rate of the patient, and should always begin with the minimum doses (Class IIb, Level B).</li><li class="elsevierStyleListItem" id="list0540">4.In cases of glomerulonephritis associated to HCV infection, antiviral therapy should be addressed in order to eliminate the antigen stimulated process. (Class IIa, Level C).</li></ul>Treatment of Acute HepatitisIt has been found that treatment of acute episodes of HCV infection not only gives more satisfactory responses, but also prevents chronic infection. In a metaanalysis of 16 studies, it was observed a difference in the risk of evolving to a chronic state after treatment of 49% (95% confidence interval, 33%–65%).Several studies have also demonstrated a preference for initiating treatment 12 weeks after virus identification, allowing some time for the spontaneous disappearance of the virus in that period (52%–67%). Spontaneous resolution tends to occur in patients with genotype 3, low viral load, female sex, and white ethnicity; black ethnicity, HIV coinfection, and advanced age favor viral persistence and chronic disease.It has been observed that patients with jaundice and fluctuating viremia seem to benefit from late treatment, whereas patients with HCV genotype 1 and high viral load respond better to early treatment.There is no consensus about optimal treatment doses. Several studies have found satisfactory responses with monotherapy of interferon at doses of 5 million U/day for a minimum of 8 weeks, or pegylated interferon alpha 2b at doses above 1.2–1.33 mg/kg/week for 12 weeks. Although high doses of interferon seem to have more benefit, there are no studies that show any noteworthy benefit with the combined use of ribavirin or with schemes longer than 12 weeks.Recommendations<ul class="elsevierStyleList" id="li0115"><li class="elsevierStyleListItem" id="list0545">1.Every patient with acute HCV infection without negative characteristics for spontaneous clearance (genotype 1, black race, HIV coinfection, or advanced age) must be under careful surveillance for 12 weeks before initiation of treatment because of the possibility of a spontaneous resolution (Class IIa, Level A).</li><li class="elsevierStyleListItem" id="list0550">2.Treatment ought to be initiated with monotherapy of pegylated interferon 1.2 mg/kg/week for at least 12 weeks or interferon 5 million U/day for a minimum of 8 weeks (Class IIa, Level B).</li></ul>Treatment of Hcv/Hbv CoinfectionHepatitis C and B viruses are the most frequent causes of chronic liver disease worldwide and coinfection may occur because they share the same routes of transmission. Coinfection with these two viruses implies a more serious disease because it has a greater risk of progression to HCC than HCV monoinfection. It is calculated that between 9% and 30% of patients with HCV are coinfected with HBV. Several studies have proven that HCV infection may suppress HBV replication, thereby diminishing HBV surface antigen (HBsAg) and core antigen (HBcAg) expression, an effect that is mainly observed in patients with genotype 1 HCV in which HBV diagnosis may be delayed for up to 6 weeks.Treatment of patients coinfected with HCV and HBV must be considered because of the probability that they will develop cirrhosis and decompensated liver disease.Liver transplantation should be considered in decompensated patients. Likewise, antiviral treatment must be selected on the basis of serological indices (HBeAg, anti-HBe) and levels of HBV DNA and HCV RNA, in order to know what virus replication is predominating. Several studies have demonstrated that combined therapy with interferon alpha 2b at doses of 6 million units three times per week for 12 weeks, followed by 3 million units three times per week for another 12 weeks plus ribavirin 1,200 mg daily for 24 weeks is effective in these patients. Recent data show that peginterferon alpha 2a (180 mg) weekly for 48 weeks and ribavirin (1,000–1,200 mg) daily is equally effective in patients with HCV monoinfection and in those with chronic HBV/HCV coinfection.<a class="elsevierStyleCrossRef" href="#bib0355">71</a> Some authors recommend combined therapy with lamivudine at doses of 100 mg daily. Both therapeutic regimens show an adequate clearance response.Recommendations<ul class="elsevierStyleList" id="li0120"><li class="elsevierStyleListItem" id="list0555">1.Combined treatment with pegylated interferon plus ribavirin and triple antiviral treatments both give similar rates of SVR and are the currently recommended treatment (Class IIa, Level B).</li></ul>Treatment for Hcv and Hiv CoinfectionApproximately 25% of HIV-infected patients are coinfected with HCV. Thus, detection tests for HCV must be performed in every HIV-infected patient and vice versa before beginning treatment, being aware that almost 6% of HIV patients do not develop anti-HCV antibodies, so HCV-RNA quantification is necessary.Several studies report that only 4% or 5% of HIV-infected patients show spontaneous resolution of their HCV infection and response to treatment is not as fast or as sustained as in patients infected only with HCV. Furthermore, coinfection promotes the development of cirrhosis as much as twice as frequently as monoinfection with HCV; this is why it must be detected in time to initiate treatment that favors antiretroviral therapy.Currently, the recommendation on treatment is pegylated interferon plus ribavirin for 48 weeks at the same doses used in HCV monoinfection. However, hemolytic anemia caused by ribavirin must be considered because it is more common in patients with this coinfection, especially when antiretroviral treatment includes zidovudine or didanosine. Interaction between didanosine and ribavirin in-creases risk of lactic acidosis and should be avoided. Interferon, on the other hand, reduces the number of CD4+ cells while maintaining their percentage, so does not favor the development of opportunistic infections. Furthermore, it has been found that patients treated with pegylated interferon show reductions of approximately 0.7 log in HIV-RNA levels.Recommendations<ul class="elsevierStyleList" id="li0125"><li class="elsevierStyleListItem" id="list0560">1.Every HIV-infected patient ought to be screened for HCV and vice versa (Class IIa, Level A).</li><li class="elsevierStyleListItem" id="list0565">2.Diagnosis of HCV in HIV-infected patients must be confirmed through HCV-RNA quantification because of the false negatives of anti-HCV antibodies that may occur in this coinfection (Class IIa, Level B).</li><li class="elsevierStyleListItem" id="list0570">3.At present, treatment with pegylated interferon plus ribavirin for 48 weeks at the same doses used in HCV monoinfected patients is recommended with strict vigilance for adverse effects (Class IIb, Level B).</li><li class="elsevierStyleListItem" id="list0575">4.Interaction between ribavirin and zidavudine and especially didanosine should be avoided. Patients receiving these antiretroviral drugs should be switched to other therapies before starting treatment for hepatitis C.</li></ul>Management of Side Effects of Hepatitis C TreatmentAlthough many HCV infections are asymptomatic, there can be side effects to drug administration. Depending on the doses, frequency, or pathway of administration, between 10% and 15% of patients suffer these side effects.Among the most common symptoms are flu-like symptoms, fatigue, headache, thyroid dysfunction, anorexia, digestive disorders, depression, and anemia. Most of these symptoms are tolerable and are easily controlled with an adjustment in dose or frequency of administration. Unfortunately, 10%–15% of patients drop out of treatment because of these symptoms, which evidently affects the response to antiviral treatment.Side effects related to the combined use of pegylated interferon plus ribavirin correspond to those produced by the separate components. The most common side effects produced by interferon are flulike symptoms, fatigue, anorexia, weight loss, alopecia, insomnia, depression, anemia, neutropenia, thrombocytopenia, and Hashimoto thyroiditis. No reports have shown an important difference between side effects of the different interferons. Among the side effects produced by ribavirin, the most frequent is hemolytic anemia and the second most common is pruritus.In cases of neutropenia (which occurs in about 30% of patients) < 750 cells/mL, the interferon dose must be reduced by half; however, in cases of neutropenia < 500 cells/mL, treatment must be suspended and reinitiated with a half-normal dose once the neutrophil count is restored. In cases of thrombocytopenia (12%), the treatment must, again, be reduced by half if values are < 50,000 cells/mm3 and suspended at values of < 20,000 cells/mm3.Although anemia is common (50%) and completely reversible with the suspension of treatment, when hemoglobin (Hb) levels are < 10 g/dL, ribavirin doses must be reduced by half. If 4 weeks after dose reduction Hb is < 8.5 g/dL, treatment must be suspended. In some cases (Hb < 12 g/dL and no contraindications), erythropoietin can be administered at doses of 40,000 to 60,000 IU/week.Depression is also common among HCV patients and is common as a side effect (6%), especially among IVDU, alcoholics, and those with multiple comorbidities. A nonhepatotoxic treatment of citalopram 5 mg/day, paroxetin 5–30 mg/day, or sertralin 25–100 mg/day is recommended.Recommendations<ul class="elsevierStyleList" id="li0130"><li class="elsevierStyleListItem" id="list0580">1.Treatment of side effects should be symptomatic and opportune to avoid treatment dropouts (Class IIa, Level A).</li><li class="elsevierStyleListItem" id="list0585">2.In cases of anemia of Hb < 10 g/dL, ribavirin doses must be reduced by half and reevaluated in 4 weeks; in cases where it continues or worsens, treatment should be suspended and erythropoietin must be administered at doses of 40,000–60,000 IU/week (Class IIa, Level B).</li><li class="elsevierStyleListItem" id="list0590">3.In cases of neutropenia with < 750 cells/mL, interferon doses should be reduced by half and suspended if neutrophils < 500 cells/mL. Treatment should be reinitiated at a half-dose once the neutrophil count is restored (Class IIa, Level B).<ul class="elsevierStyleList" id="li0135"><li class="elsevierStyleListItem" id="list0595">•A granulocyte colony stimulating factor is recommended for the treatment of neutropenia (Class IIa, Level C).</li></ul></li><li class="elsevierStyleListItem" id="list0600">4.In cases of thrombocytopenia < 50,000 cells/mm3, the interferon dose must be reduced by half or suspended if the count is < 20,000 cells/mm3(Class IIa, Level B).</li><li class="elsevierStyleListItem" id="list0605">5.Every patient with depression must be treated with citalopram 5 mg/day, paroxetin 5–30 mg/day, or sertralin 25–100 mg/day to avoid poor compliance with base treatment (Class IIa, Level B).</li></ul>New Approaches to Hcv TreatmentHCV therapy is under study in order to improve the response among patients. New options are needed because of the following two situations.<ul class="elsevierStyleList" id="li0140"><li class="elsevierStyleListItem" id="list0610">1.The response to treatment has been shown to depend on viral genotype, viral load, ethnicity, and recently the presence of the IL-28B gene, and it is noted that available therapies have lower efficacy in Latin American patients.</li><li class="elsevierStyleListItem" id="list0615">2.If disease is mild, patients can wait for better therapies.</li><li class="elsevierStyleListItem" id="list0620">3.There are several side effects of treatment with pegylated interferon and ribavirin.</li></ul>The most advanced drugs in development are the protease and polymerase inhibitors. The protease inhibitors interfere with the translation of HCV and the polymerase inhibitors act by interfering with viral replication <a class="elsevierStyleCrossRef" href="#t0045">(Table 9)</a>.<elsevierMultimedia ident="t0045"></elsevierMultimedia>Recent studies have shown that protease inhibitors such as telaprevir or boceprevir, combined with pegylated interferon and ribavirin, achieve efficacy rates of more than 70% in naïve patients with genotype 1 HCV. It has been demonstrated that the efficacy rate for white Latin Americans is around 34%.The polymerase inhibitors are either analogs or nonnucleoside inhibitors. The nucleoside analogs are active site inhibitors that require conversion to the active triphosphate. The nucleosides affect a highly conserved region of the genome and have a high genetic barrier to resistance. These inhibitors are active against genotypes 2 and 3. None of them is yet available because most are in phase 2 trials.Recommendations<ul class="elsevierStyleList" id="li0145"><li class="elsevierStyleListItem" id="list0625">1.Those infected with HCV genotype 1 or 4 who are naïve-to-treatment and without advanced liver disease could wait for direct-acting antiviral (DAA) treatment, especially because results from telaprevir-and boceprevir-based triple therapies have shown improved response rates (Class IIa, Level B).</li><li class="elsevierStyleListItem" id="list0630">2.Those infected with HCV genotype 1 or 4 with significant liver disease should be treated with pegylated interferon and ribavirin. In the case of no response, a triple therapy could be considered (Class IIa, Level C).</li></ul>Insulin Resistance, Metabolic Syndrome, and their Implications in HCV InfectionInsulin resistance (IR), defined as the pathophysiological condition in which higher than normal concentrations of insulin are required to maintain normal levels of glycemia, is closely related to the development of such pathological states as obesity, diabetes mellitus type 2 (DM2), and nonalcoholic fatty liver disease (NAFLD), which is the most frequent hepatopathy in Western countries. Several studies have found that it is present in 30% to 70% of HCV-infected patients and that it increases the risk of developing DM2 in HCV-positive patients.Hepatic steatosis is present more often in patients with HCV genotype 3, which has been implicated as pathogenic in its development. However, this has given way to the conclusion that in non-genotype 3 HCV, the cause of the steatosis is IR.In HCV-infected patients, it has been found that the worsening of IR and associated pathologies is caused by effects on the insulin receptor substrates (IRS) and the generation of proinflammatory cytokines. NAFLD is promoted because of the increase in lipogenesis caused by IR and the metabolism of fatty acids.<a class="elsevierStyleCrossRef" href="#bib0360">72</a> This, in addition to the proinflammatory state, favors its evolution to steatohepatitis, cirrhosis, and HCC.<a class="elsevierStyleCrossRef" href="#bib0365">73</a> Clinical repercussions of IR have been demonstrated in several studies in which it was concluded that IR diminishes the response to antiviral treatment independent of the viral genotype, evolution of liver damage and fibrosis, or development of DM2.Some studies have suggested that reduction of body weight before initiating HCV treatment gives a better response. They have also suggested the use of insulin-sensitizing agents such as pioglitazone and metformin, and although the studies have found some differences that favor late virological response (LVR) or slightly favor SVR, they have failed to find a significant improvement with the use of these agents, for which more studies are needed.<a class="elsevierStyleCrossRefs" href="#bib0370">74</a>-<a class="elsevierStyleCrossRef" href="#bib0380">76</a>Recommendations<ul class="elsevierStyleList" id="li0150"><li class="elsevierStyleListItem" id="list0635">1.All HCV-infected patients must have a metabolic assessment that includes HOMA-IR measurement (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0640">2.Weight loss ought to be recommended in all HCV-infected patients who are overweight or obese, preferably before initiation of HCV treatment (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0645">3.Use of insulin-sensitizing agents must be individualized depending on comorbidities (Class IIb, Level B).</li></ul>Hepatitis C and Hepatocellular Carcinoma (Hcc)In several regions of the world (especially in Asia and Africa), a strong association is found between HBV infection, HCV, and alcoholic cirrhosis, and the development of HCC. In Oceania and both North and South America, the last two entities tend to be the principal risk factors in the development of this hepatic neoplasm. Small multicenter studies in some regions of America and Latin America confirm the presence of HCV in patients with HCC.Several risk factors have been related to the genesis of HCC. The main risk factor in HCV-infected patients is the presence of cirrhosis. Although the incidence is much lower in noncirrhotic patients, there are also other risk factors related to host, virus, and some external factors. For the host, risk factors include advanced age (> 50 years), male sex, thrombocytopenia, esophageal varices, and comorbidities. For viral variables, a controversial meta-analysis showed that patients with HCV genotype 1b have twice the normal risk of developing HCC. Other studies, also meta-analyses, report that active or occult, but not past, HBV infection correlates with the development of this pathology, whereas HIV coinfection promotes the advance to cirrhosis. Finally, for external factors, heavy alcohol intake doubles the possibility of evolution to HCC compared with those who do not drink. Treatment with interferon for any other cause besides hepatitis C acts as protection against the development of HCC.Recommendations<ul class="elsevierStyleList" id="li0155"><li class="elsevierStyleListItem" id="list0650">1.Every patient with HCV must be monitored because of the risk of developing HCC, especially those with cirrhosis, HBV or HIV coinfection, or chronic alcoholism (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0655">2.Monitoring must be performed by ultrasonography every 6 months (Class IIa, Level A).</li></ul>Hepatitis C Treatment: Cost-Efficacy, Cost-BenefitThe impact of HCV infection is high and will tend to increase in the future. There are registers in some Latin American countries that suggest that the infection is the second most frequent cause of cirrhosis and that its prevalence will increase to more than 70%. It also favors the evolution of liver disease from the infiltrative stage to inflammatory, necroinflammatory, and neoplasmic stages with their corresponding functional loss and diminishment in quality-adjusted life years.Objectives of treatment are to eliminate the virus and stop the progression of liver damage. To do so, SVR is valued because it is associated with improvement of liver function, liver histology, and quality of life. Pegylated interferon combined with ribavirin is currently considered the therapy with the best response. Some models indicate that if this treatment were given to 10% of infected patients, a reduction of 6% in morbidity and 4% in mortality would occur, and if it were given to 50% of patients the reductions would be of 26% and 20%, respectively.Recommendations<ul class="elsevierStyleList" id="li0160"><li class="elsevierStyleListItem" id="list0660">1.Preventive measures must be emphasized and actions directed to minimize risk factors should be taken in order to reduce the incidence of infection (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0665">2.Every HCV-infected patient must have individualized treatment analyzing his/her predictive and risk factors in order to reduce morbidity and mortality caused by the infection (Class I, Level B).</li><li class="elsevierStyleListItem" id="list0670">3.Elective treatment for patients with no associated risk factors must be with combined pegylated interferon plus ribavirin (Class I, Level A).</li></ul>Medical and Legal Implications of Hepatitis CHCV infection is a worldwide public health issue. There are many routes of transmission that are used to define certain risk groups: patients with a history of blood transfusion before 1992, hemophiliacs, IVDU, patients in treatment with hemodialysis, patients who have had acupuncture, patients with tattoos, patients with multiple sexual partners, newborns to infected mothers, and healthcare workers. Prevalence in this last group, for which healthcare worker-patient, patient-healthcare worker, and patient-patient transmission is a reality, varies from 1% to 10%. The first and second routes occur especially among surgeons who are in direct contact with patient tissues during any interven-tion; the third route is more obvious given the outbreaks in some hemodialysis centers.Currently, prevention is considered the main route to avoid viral transmission. Screening of every blood donor and of every patient with documented IV drug use, history of transfusion before 1992, in hemodialysis, or with evidence of hepatopathy is recommended. Use of body protection for healthcare personnel is another recommendation. Not every country recommends routine screening within this group, but usually only after exposure.There are no regulations to follow post exposure. Each institution follows its own protocol. Generally it is recommended to wash the exposed site (antiseptics and disinfectants have not provided better preventive indexes, but neither are they contraindicated) and to screen both the medical personnel and the patient for HBV, HCV, and HIV. Although there is no indication for suspending normal activities, some countries, such as Germany, do promote it until viral loads of less than 1 x 10<a class="elsevierStyleCrossRef" href="#bib0015">3</a> IU/mL are reported.Recommendations<ul class="elsevierStyleList" id="li0165"><li class="elsevierStyleListItem" id="list0675">1.Routine screening of every patient with the following risk factors: hemotransfused before 1992, IVDU, and/or people with multiple sexual partners or with any identified liver disease (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0680">2.Routine screening of healthcare workers (Class IIb, Level C).</li><li class="elsevierStyleListItem" id="list0685">3.Use of body protection for medical personnel at every point during which contact is established with exposed patient tissues (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0690">4.Reinforcement of healthcare personnel education regarding protection and techniques of injection, taking of blood samples, minor surgeries, and other procedures in which they have contact with exposed patients’ blood (Class I, Level A).</li><li class="elsevierStyleListItem" id="list0695">5.In case of exposure of the healthcare worker to patient blood products, the exposure site must be washed with soap and water, and samples for HBV, HCV, and HIV analysis taken for both the healthcare worker and the patient (Class I, Level A). The following steps should be taken:<ul class="elsevierStyleList" id="li0170"><li class="elsevierStyleListItem" id="list0700">•Measure ALT activity.</li><li class="elsevierStyleListItem" id="list0705">•Follow up with new blood samples of the affected healthcare worker in 4–6 months.</li><li class="elsevierStyleListItem" id="list0710">•Confirm diagnosis of HCV with HCV-RNA quantification or anti-HCV by RIBA.</li></ul></li></ul>" "textoCompletoSecciones" => array:1 [ "secciones" => array:27 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Preamble" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Introduction" ] 2 => array:3 [ "identificador" => "sec0015" "titulo" => "Epidemiology" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Recommendations" ] ] ] 3 => array:3 [ "identificador" => "sec0025" "titulo" => "Transmission Routes" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Recommendations" ] ] ] 4 => array:3 [ "identificador" => "sec0035" "titulo" => "Diagnosis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Recommendations" ] ] ] 5 => array:3 [ "identificador" => "sec0045" "titulo" => "Utility of Liver Biopsy in Chronic Infection" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Recommendations" ] ] ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Use of Noninvasive Methods to Evaluate The Stage of Liver Fibrosis" ] 7 => array:3 [ "identificador" => "sec0060" "titulo" => "Indications and Contraindications for the Treatment of Hcv Infection" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Recommendations" ] ] ] 8 => array:3 [ "identificador" => "sec0070" "titulo" => "Predictive Factors for the Response to Treatment" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Recommendations" ] ] ] 9 => array:3 [ "identificador" => "sec0080" "titulo" => "Hepatitis C Treatment in Naïve Patients" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Recommendations" ] ] ] 10 => array:3 [ "identificador" => "sec0090" "titulo" => "Approach and Management of Patients With Normal Levels of Transaminases" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Recommendations" ] ] ] 11 => array:3 [ "identificador" => "sec0100" "titulo" => "Treatment in Cirrhotic Patients" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0105" "titulo" => "Recommendations" ] ] ] 12 => array:3 [ "identificador" => "sec0110" "titulo" => "Treatment in Posttransplantation Patients" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0115" "titulo" => "Recommendations" ] ] ] 13 => array:3 [ "identificador" => "sec0120" "titulo" => "Treatment in Nonresponders and Relapsers" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0125" "titulo" => "Recommendations" ] ] ] 14 => array:3 [ "identificador" => "sec0130" "titulo" => "Management of Hcv Infection in Pregnant Women" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0135" "titulo" => "Recommendations" ] ] ] 15 => array:3 [ "identificador" => "sec0140" "titulo" => "Management of Hcv Infection in Children" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0145" "titulo" => "Recommendations" ] ] ] 16 => array:3 [ "identificador" => "sec0150" "titulo" => "Treatment of HCV-Infected Patients with Kidney Disease" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0155" "titulo" => "Recommendations" ] ] ] 17 => array:3 [ "identificador" => "sec0160" "titulo" => "Treatment of Acute Hepatitis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0165" "titulo" => "Recommendations" ] ] ] 18 => array:3 [ "identificador" => "sec0170" "titulo" => "Treatment of Hcv/Hbv Coinfection" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0175" "titulo" => "Recommendations" ] ] ] 19 => array:3 [ "identificador" => "sec0180" "titulo" => "Treatment for Hcv and Hiv Coinfection" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0185" "titulo" => "Recommendations" ] ] ] 20 => array:3 [ "identificador" => "sec0190" "titulo" => "Management of Side Effects of Hepatitis C Treatment" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0195" "titulo" => "Recommendations" ] ] ] 21 => array:3 [ "identificador" => "sec0200" "titulo" => "New Approaches to Hcv Treatment" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0205" "titulo" => "Recommendations" ] ] ] 22 => array:3 [ "identificador" => "sec0210" "titulo" => "Insulin Resistance, Metabolic Syndrome, and their Implications in HCV Infection" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0215" "titulo" => "Recommendations" ] ] ] 23 => array:3 [ "identificador" => "sec0220" "titulo" => "Hepatitis C and Hepatocellular Carcinoma (Hcc)" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0225" "titulo" => "Recommendations" ] ] ] 24 => array:3 [ "identificador" => "sec0230" "titulo" => "Hepatitis C Treatment: Cost-Efficacy, Cost-Benefit" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0235" "titulo" => "Recommendations" ] ] ] 25 => array:3 [ "identificador" => "sec0240" "titulo" => "Medical and Legal Implications of Hepatitis C" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0245" "titulo" => "Recommendations" ] ] ] 26 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:9 [ 0 => array:6 [ "identificador" => "t0005" "etiqueta" => "Table 1." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Adapted from: Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management and treatment of hepatitis C: an update. Hepatology 2009; 49(4): 1335–74." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Classification \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Description \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Class I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Conditions for which there is evidence or general consensus that the particular diagnostic procedure or treatment is beneficial, useful, and effective. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Class II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Conditions for which there is conflicting evidence and/or divergence in opinions about the utility and efficacy of a diagnostic evaluation, procedure, or treatment. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Class IIa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">The weight of evidence/opinion is in favor of utility and efficacy. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Class IIb \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">The utility and/or efficacy are less well established by evidence or opinion. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Class III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Conditions in which there is evidence or general consensus that a diagnostic evaluation, procedure, or treatment is not useful or effective and in some cases may cause damage. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066301.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Evidence level \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Description \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Level A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Data derived from multiple randomized studies or meta-analysis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Level B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Data derived from only one randomized study or nonrandomized studies. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Level C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Experts’ opinions, case studies, or treatment standards. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066299.png" ] ] ] ] ] 1 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Country \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">General population \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Blood donors \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">IVDU \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Hemodialysis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Coinfection with HBV \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Mexico \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">6.7%<a class="elsevierStyleCrossRef" href="#t2fn1">2</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Dominican Republic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">2.4%<a class="elsevierStyleCrossRef" href="#t2fn1">4</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">49% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Puerto Rico \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">2.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Costa Rica \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.3–2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.2–0.3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0%<a class="elsevierStyleCrossRef" href="#t2fn1">1</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Venezuela \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">71%<a class="elsevierStyleCrossRef" href="#t2fn1">3</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Brazil \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.32% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Peru \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">51% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Chile \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">2.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">0.79% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">62% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">19% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">30% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066302.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "t2fn1" "etiqueta" => "1" "nota" => "Patiño J, Hevia F, Saenz R, Nuñez P, Rodríguez R, Horwitz D, Flores J. Trabajo 69 XIII Jornadas Latinoamericanas de Hepatologia. Rev Gastroenterol Mex 1994; 59(suppl. 2). 2Méndez-Sánchez N, Motola-Kuba D, Chávez-Tapia NC, et al. Prevalence of hepatitis C virus infection among hemodialysis patients at a tertiary-care hospital in Mexico City, Mexico. J Clin Microbiol 2004; 42: 4321–2. 3Pujol FH, Ponce JG, Lema MG, et al. High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence. J Clin Microbiol 1996; 34: 1633–6. 4Hogar Crea Dominicano. Propuesta para proyecto. Proyecto de capacitación y sensibilización en relación a las ITS el VIH y el SIDA con ex-usuarios de drogas (UD) comunidades residenciales de Hogar Crea Dominicano., Inc." ] ] ] "descripcion" => array:1 [ "en" => "Prevalence of HCV in different risk groups." ] ] 2 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 3." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Stage \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">IASL<a class="elsevierStyleCrossRef" href="#t3fn1">1</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Metavir<a class="elsevierStyleCrossRef" href="#t3fn1">2</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Non fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Non fibrosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Mild fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Periportal fibrotic expansion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Moderate fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Periportal septa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Severe fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Portocentral septa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066303.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "t3fn1" "etiqueta" => "1" "nota" => "Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19: 1513–20. 2Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR cooperative study group. Hepatology 1996; 24: 289–93." ] ] ] "descripcion" => array:1 [ "en" => "Fibrosis evaluation scales." ] ] 3 => array:7 [ "identificador" => "t0020" "etiqueta" => "Table 4." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"><ul class="elsevierStyleList" id="li0005"><li class="elsevierStyleListItem" id="list0005">•Age 18 to 70 years.</li><li class="elsevierStyleListItem" id="list0010">•HCV antibody positive in serum.</li><li class="elsevierStyleListItem" id="list0015">•Positive for HCV RNA.</li><li class="elsevierStyleListItem" id="list0020">•Hepatic biopsy: chronic hepatitis with significant fibrosis.</li><li class="elsevierStyleListItem" id="list0025">•Compensated liver disease.<ul class="elsevierStyleList" id="li0010"><li class="elsevierStyleListItem" id="list0030">°Absence of gastroesophagic varicose veins.</li><li class="elsevierStyleListItem" id="list0035">°Total bilirubin < 1.5 g/dL.</li><li class="elsevierStyleListItem" id="list0040">°International normalized ratio (INR) < 1.5.</li><li class="elsevierStyleListItem" id="list0045">°Albumin > 3.4 g/100mL.</li><li class="elsevierStyleListItem" id="list0050">°Platelet count of 75,000/mm3.</li><li class="elsevierStyleListItem" id="list0055">°No evidence of hepatic decompensation (hepatic encephalopathy or ascites).</li></ul></li><li class="elsevierStyleListItem" id="list0060">•Hemoglobin ≥ 13 g/dL for men and 12 g/dL for women.</li><li class="elsevierStyleListItem" id="list0065">•Neutrophil count ≥ 1500/mm3.</li><li class="elsevierStyleListItem" id="list0070">•Creatinine < 1.5 mg/dL.</li><li class="elsevierStyleListItem" id="list0075">•Willingness to be treated.</li><li class="elsevierStyleListItem" id="list0080">•No contraindications.</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066294.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of patients for whom therapy is recommended." ] ] 4 => array:7 [ "identificador" => "t0025" "etiqueta" => "Table 5." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"><ul class="elsevierStyleList" id="li0015"><li class="elsevierStyleListItem" id="list0085">•Major uncontrolled depressive disorder and other mental disturbances.</li><li class="elsevierStyleListItem" id="list0090">•Posttransplantation patients.</li><li class="elsevierStyleListItem" id="list0095">•Autoimmune diseases that might be exacerbated by treatment with pegylated interferon.</li><li class="elsevierStyleListItem" id="list0100">•Untreated thyroid disease.</li><li class="elsevierStyleListItem" id="list0105">•Pregnancy.</li><li class="elsevierStyleListItem" id="list0110">•Severe comorbidity such as arterial hypertension, heart failure, uncontrolled diabetes mellitus, chronic obstructive pulmonary disease, or epilepsy.</li><li class="elsevierStyleListItem" id="list0115">•Age under 2 years.</li><li class="elsevierStyleListItem" id="list0120">•Known hypersensitivity to treatment.</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066296.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Contraindications for HCV treatment." ] ] 5 => array:7 [ "identificador" => "t0030" "etiqueta" => "Table 6." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Modified from: Jen J, Laughlin M, Chung C, et al. Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther 2002; 72(4): 349–61." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Weight (kg) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Ribavirin dose (mg) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">< 65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">800 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">65–85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1,000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">85–105 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1,200 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">> 105 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">1,400 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066298.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Ribavirin dose by weight." ] ] 6 => array:7 [ "identificador" => "t0035" "etiqueta" => "Table 7." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Airoldi J, Berghella V. Hepatitis C and pregnancy. Obst Gynecol Surv 2006; 61: 10. Plunkett B, Grobman W. Routine hepatitis C virus screening in pregnancy: A cost-effectiveness analysis. Am J Obst Gynecol 2005; 192:1153–61." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"><ul class="elsevierStyleList" id="li0020"><li class="elsevierStyleListItem" id="list0125">•Women with history of blood derivatives transfusion especially before 1992.</li><li class="elsevierStyleListItem" id="list0130">•Women with history of IVDU.</li><li class="elsevierStyleListItem" id="list0135">•Patients and healthcare workers involved in dialysis programs.</li><li class="elsevierStyleListItem" id="list0140">•Women with HIV or HBV infection.</li><li class="elsevierStyleListItem" id="list0145">•Sexual partners of patients infected with HIV, HBV, or HCV.</li><li class="elsevierStyleListItem" id="list0150">•Women with a history of tattooing and/or piercing.</li><li class="elsevierStyleListItem" id="list0155">•Transplantation recipients especially before 1992.</li><li class="elsevierStyleListItem" id="list0160">•Women with high levels of transaminases.</li><li class="elsevierStyleListItem" id="list0165">•Participants in in vitro fertilization programs with anonymous donors.</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066295.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Indications for screening in pregnant women." ] ] 7 => array:7 [ "identificador" => "t0040" "etiqueta" => "Table 8." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "IFN: Interferon. GFR: Glomerular filtration rate. Modified from: Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, Management and treatment of Hepatitis C: An update. Hepatology 2009; 49(4):1335–74." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Stage \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Description \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Kidney damage with conserved or slightly elevated GFR (> 90 mL/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Usual combined therapy depending on viral genotype. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Kidney damage with mildly affected GFR (60–90 mL/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Usual combined therapy depending on viral genotype. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Moderately affected GFR (30–59 mL/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2b 1 μg/kg/week; or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2a 135 μg/kg/week + Ribavirin 200–800 mg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Severely affected GFR (15–29 mL/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2b 1 μg/kg/week; or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2a 135 μg/kg/week + Ribavirin 200–800 mg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Chronic renal failure (GFR < 15 mL/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2b 1 μg/kg/week; or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2a 135 μg/kg/week + Ribavirin 200–800 mg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">5D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Dialysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">IFN 2a or 2b 3 mU/3 times per week; or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2b 1 μg/kg/week; or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2a, 135 μg/kg/week + Ribavirin 200–800 mg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Cryoglobulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Control of the acute event with immunosuppressants and then: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">INF2a or 2b 3 mU/3 times per week; or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2b 1 μg/kg/week; or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">PegIFNα-2a, 135 μg/kg/week + Ribavirin 200–800 mg \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066297.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Treatment according to stage of renal dysfunction." ] ] 8 => array:7 [ "identificador" => "t0045" "etiqueta" => "Table 9." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Enzyme inhibi tors \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Genome sequence-based \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Others \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Protease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">RNA interference \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Modifications of IFN and ribavirin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Albinterferon \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-PEGIFN lambda (IL-29) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Taribavirin (viramidine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Polymerase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Antisense \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Immunological \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Therapeutic vaccines \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Toll-like receptor agonists \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Hepatitis C immunoglobulin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Monoclonal antibodies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">NS5A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">Targeting cellular factors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Cyclophilin antagonists \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Nitazoxanide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-mIR-122 inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">-Entry inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2066300.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Emer ging Therapies for HCV. Specifically targeted antiviral treatment (STAT-C)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:76 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Discovery of the Hepatitis C virus." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Houghton M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2008.01925.x" "Revista" => array:7 [ "tituloSerie" => "Liver Int" "fecha" => "2009" "volumen" => "29" "numero" => "S1" "paginaInicial" => "82" "paginaFinal" => "88" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19207970" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "National consensus of Hepatitis C." "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Coordinación General de los Institutos Nacionales de Salud, Asociación Mexicana de Hepatología." "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2002" "volumen" => "1" "numero" => "3" "paginaInicial" => "148" "paginaFinal" => "154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15280815" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estimating the future health burden of chronic hepatitis C and human immunodeficiency virus infections in the United States." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Deuffic-Burban S" 1 => "Poynard T" 2 => "Sulkowski MS" 3 => "Wong JB" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2006.00785.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2007" "volumen" => "14" "paginaInicial" => "107" "paginaFinal" => "115" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17244250" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Trends in liver disease prevalence in Mexico from 2005 to 2050 through mortality data." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Méndez-Sánchez N" 1 => "Villa AR" 2 => "Chavez-Tapia N" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2005" "volumen" => "4" "numero" => "1" "paginaInicial" => "52" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15798662" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Projecting future complications of chronic hepatitis C in the United States." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Davis GL" 1 => "Albright JE" 2 => "Cook SF" 3 => "Rosenberg DM" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jlts.2003.50073" "Revista" => array:6 [ "tituloSerie" => "Liver Transpl" "fecha" => "2003" "volumen" => "9" "paginaInicial" => "331" "paginaFinal" => "338" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12682882" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis, management and treatment of Hepatitis C: An update." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Ghany MG" 1 => "Strader DB" 2 => "Thomas DL" 3 => "Seeff LB" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.22759" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2009" "volumen" => "49" "numero" => "4" "paginaInicial" => "1335" "paginaFinal" => "1374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19330875" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of hepatitis B and C viruses: A global overview." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Te HS" 1 => "Jensen DM" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Liv Dis" "fecha" => "2010" "volumen" => "14" "paginaInicial" => "1" "paginaFinal" => "21" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low prevalence of anti-hepatitis C virus antibodies in Mexico: A systematic review." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Chiquete E" 1 => "Panduro A" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000096306" "Revista" => array:6 [ "tituloSerie" => "Intervirology" "fecha" => "2007" "volumen" => "50" "paginaInicial" => "1" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17164551" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Seroprevalencia de la hepatitis C en adultos de México: ¿Un problema de salud pública emergente?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Valdespino JL" 1 => "Conde-González CJ" 2 => "Olaiz-Fernández G" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Salud Pública Mex" "fecha" => "2007" "volumen" => "49" "numero" => "Suppl 3" "paginaInicial" => "S395" "paginaFinal" => "S403" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Pereira MLB et al. Congresso Brasileiro de Hepatologia. 2009." ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Secretaría de Estado de Salud Pública y Asistencia Social (SESPAS). Enfermedad Hepatitis C. Santo Domingo R.D." ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Seroepidemiology of viral hepatitis, HIV and herpes simplex type 2 in the household population aged 21-64 years in Puerto Rico." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Pérez M" 1 => "Marrero E" 2 => "Meléndez M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2334-10-76" "Revista" => array:5 [ "tituloSerie" => "BMC Infect Dis" "fecha" => "2010" "volumen" => "10" "paginaInicial" => "76" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20331884" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Santana B, Guerrero F. Prevalencia de infecciones de transmisión sexual en mujeres residentes en Bateyes del ingenio Barahona. Organización Panamericana de la Salud OPS/OMS. Programa conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA). 2001." ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Presentaciones en even-tos nacionales." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Hevia F" 1 => "San Roman M" 2 => "Aguero O" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Revista Médica de Costa Rica" "fecha" => "1992" "paginaInicial" => "518" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Hevia F, San Roman M, Aguero O. Hepatitis virales 1993." ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Hevia F, San Roman M, Aguero O. Medicina Legal de Costa Rica 1994; 11" ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of hepatitis C virus in Peru and Latin America." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Dávalos Moscol M" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Gastroenterol Peru" "fecha" => "2009" "volumen" => "29" "paginaInicial" => "347" "paginaFinal" => "354" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20066020" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence and prevalence of hepatitis C virus infection in Chile." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "González R" 1 => "Soza A" 2 => "Hernández V" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Hepatol." "fecha" => "2005" "volumen" => "4" "paginaInicial" => "127" "paginaFinal" => "130" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16010246" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "“Hepatitis C en Chile: Magnitud del problema”." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Soza A" 1 => "López-Lastra M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "/S0034-98872006000600016" "Revista" => array:6 [ "tituloSerie" => "Rev Med Chil" "fecha" => "2006" "volumen" => "134" "paginaInicial" => "777" "paginaFinal" => "788" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17130955" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Schroder T y la Asociación Argentina para el Estudio de las Enfermedades del Hfgado. Conclusiones del Consenso Argentino Hepatitis C 2007." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Fassio E" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Gastroenter Latinoamer" "fecha" => "2008" "volumen" => "38" "paginaInicial" => "56" "paginaFinal" => "74" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The changing epidemiology of hepatitis C virus infection in Europe." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Esteban JI" 1 => "Sauleda S" 2 => "Quer J" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2007.07.033" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2008" "volumen" => "48" "paginaInicial" => "148" "paginaFinal" => "162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18022726" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for hepatitis C virus infection in United States blood donors. NHLBI Retrovirus Epidemiology Donor Study (REDS)." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Murphy EL" 1 => "Bryzman SM" 2 => "Glynn SA" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.510310329" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2000" "volumen" => "31" "paginaInicial" => "756" "paginaFinal" => "762" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10706569" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transmission of hepatitis C virus from mothers to infants. The Vertical Transmission of Hepatitis C Virus Collaborative Study Group." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Ohto H" 1 => "Terazawa S" 2 => "Sasaki N" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199403173301103" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1994" "volumen" => "330" "paginaInicial" => "744" "paginaFinal" => "750" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8107740" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mother-to-infant transmission of hepatitis C virus. Lombardy Study Group on Vertical HCV Transmission." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Zanetti AR" 1 => "Tanzi E" 2 => "Paccagnini S" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0140-6736(95)90277-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1995" "volumen" => "345" "paginaInicial" => "289" "paginaFinal" => "291" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7530793" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "McIntyre PG" 1 => "Tosh K" 2 => "McGuire W" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2006" "paginaInicial" => "CD005546" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of hepatitis C virus infection among hemodialysis patients at a tertiary-care hospital in Mexico City, Mexico." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Méndez-Sánchez N" 1 => "Motola-Kuba D" 2 => "Chavez-Tapia NC" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.42.9.4321-4322.2004" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2004" "volumen" => "42" "paginaInicial" => "4321" "paginaFinal" => "4322" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15365034" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Pujol FH" 1 => "Ponce JG" 2 => "Lema MG" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "1996" "volumen" => "34" "paginaInicial" => "1633" "paginaFinal" => "1636" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8784559" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MMWR Recomm Rep" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis." "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "fecha" => "2001" "volumen" => "50" "paginaInicial" => "1" "paginaFinal" => "52" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Natural history of chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Seeff LB" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2002.36806" "Revista" => array:8 [ "tituloSerie" => "Hepatology" "fecha" => "2002" "volumen" => "36" "numero" => "Suppl" "paginaInicial" => "S35" "paginaFinal" => "S46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12407575" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S014067361161516X" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How can we predict treatment response?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Selzner N MI" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "editores" => "Al Ave" "titulo" => "Advances in the Therapy of Liver Disease." "paginaInicial" => "271" "paginaFinal" => "277" "serieFecha" => "1997" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomized trial." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Manns MP" 1 => "McHutchison JG" 2 => "Gordon SC" 3 => "Rustgi VK" 4 => "Shiffman M" 5 => "Reindollar R" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0140-6736(01)06102-5" "Revista" => array:8 [ "tituloSerie" => "Lancet" "fecha" => "2001" "volumen" => "358" "numero" => "9286" "paginaInicial" => "958" "paginaFinal" => "965" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11583749" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1474442203004022" "estado" => "S300" "issn" => "14744422" ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Fried MW" 1 => "Shiffman ML" 2 => "Reddy KR" 3 => "Smith C" 4 => "Marinos G" 5 => "Goncales FLJ" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa020047" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2002" "volumen" => "347" "numero" => "13" "paginaInicial" => "975" "paginaFinal" => "982" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12324553" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus: A critical appraisal of approaches to therapy." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Nelson DR" 1 => "Davis GL" 2 => "Jacobson I" 3 => "Everson GT" 4 => "Fried MW" 5 => "Harrison SA" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2008.11.016" "Revista" => array:7 [ "tituloSerie" => "Clin Gastroenterol Hepatol" "fecha" => "2009" "volumen" => "7" "numero" => "4" "paginaInicial" => "397" "paginaFinal" => "414" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19114127" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adherence to combination therapy enhances sustained response in genotype 1 infected patients with chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "McHutchinson JG" 1 => "Manns M" 2 => "Patel K" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2002" "volumen" => "123" "paginaInicial" => "1061" "paginaFinal" => "1069" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12360468" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic variation in IL-28B predicts hepatitis C treatment-induced viral clearance." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Ge D" 1 => "Fellay J" 2 => "Thompson AJ" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature08309" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2009" "volumen" => "461" "paginaInicial" => "399" "paginaFinal" => "401" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19684573" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: Systematic review of randomized trials." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Awad T" 1 => "Thorlund K" 2 => "Hauser G" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.23504" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2010" "volumen" => "51" "numero" => "4" "paginaInicial" => "1176" "paginaFinal" => "1184" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20187106" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peginterferon alpha 2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Hadziyannis SJ" 1 => "Sette H Jr" 2 => "Morgan TR" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-140-5-200403020-00010" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2004" "volumen" => "140" "paginaInicial" => "346" "paginaFinal" => "355" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14996676" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of liver disease in a population of asymptomatic individuals with hepatitis C virus infection." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Alberti A" 1 => "Noventa F" 2 => "Benvegnù L" 3 => "Boccato S" 4 => "Gatta A" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-137-12-200212170-00009" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2002" "volumen" => "137" "paginaInicial" => "961" "paginaFinal" => "964" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12484711" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Volunteer blood donors with antibody to hepatitis C virus: Clinical, biochemical, virologic, and histologic features." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Shakil AO" 1 => "Conry-Cantilena C" 2 => "Alter HJ" 3 => "Hayashi P" 4 => "Kleiner DE" 5 => "Tedeschi V" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-123-5-199509010-00002" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1995" "volumen" => "123" "paginaInicial" => "330" "paginaFinal" => "337" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7542854" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus carriers with persistently normal aminotransferase levels: healthy people or true patients?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Puoti C" 1 => "Castellacci R" 2 => "Montagnese F" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Dig Liver Dis" "fecha" => "2000" "volumen" => "32" "paginaInicial" => "634" "paginaFinal" => "643" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11142566" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Puoti C" 1 => "Magrini A" 2 => "Stati T" 3 => "Rigato P" 4 => "Montagnese F" 5 => "Rossi P" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.1997.v26.pm0009397976" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1997" "volumen" => "26" "paginaInicial" => "1393" "paginaFinal" => "1398" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9397976" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Viral and metabolic factors influencing alanine aminotransferase activity in patients with chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Prati D" 1 => "Shiffman ML" 2 => "Diago M" 3 => "Gane E" 4 => "Rajender Reddy K" 5 => "Pockros P" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2006.01.004" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "679" "paginaFinal" => "685" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16487620" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Piton A" 1 => "Poynard T" 2 => "Imbert-Bismut F" 3 => "Khalil L" 4 => "Delattre J" 5 => "Pelissier E" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.510270505" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1998" "volumen" => "27" "paginaInicial" => "1213" "paginaFinal" => "1219" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9581673" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HCV carriers with persistently normal aminotransferase levels: Normal does not always mean healthy." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Puoti C" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2003" "volumen" => "38" "paginaInicial" => "529" "paginaFinal" => "532" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12663249" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Braks RE" 1 => "Ganne-Carrie N" 2 => "Fontaine H" 3 => "Paries J" 4 => "Grando-Lemaire V" 5 => "Beaugrand M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v13.i42.5648" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "5648" "paginaFinal" => "5653" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17948941" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin. Review." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Berenguer M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2008.05.002" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2008" "volumen" => "49" "paginaInicial" => "274" "paginaFinal" => "287" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18571272" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Peveling-Oberhag J" 1 => "Zeuzem S" 2 => "Hofmann WP" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00430-009-0131-8" "Revista" => array:6 [ "tituloSerie" => "Med Microbiol Immunol" "fecha" => "2010" "volumen" => "199" "paginaInicial" => "1" "paginaFinal" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19902246" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of hepatitis C in liver transplant recipients." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Gordon FD" 1 => "Kwo P" 2 => "Vargas HE" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Liver Transplant" "fecha" => "2009" "volumen" => "15" "paginaInicial" => "126" "paginaFinal" => "135" ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C and liver transplantation." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Brown RS" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature04083" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2005" "volumen" => "436" "paginaInicial" => "973" "paginaFinal" => "978" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16107838" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of hepatitis C cirrhosis after liver transplantation." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Firpi RJ" 1 => "Clark V" 2 => "Soldevila-Pico C" 3 => "Morelli G" 4 => "Cabrera R" 5 => "Levy C" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Liver Transplant" "fecha" => "2009" "volumen" => "15" "paginaInicial" => "1063" "paginaFinal" => "1071" ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "51." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Everson GT" 1 => "Trotter J" 2 => "Forman L" 3 => "Kugelmas M" 4 => "Halprin A" 5 => "Fey B" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20793" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2005" "volumen" => "42" "paginaInicial" => "255" "paginaFinal" => "262" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16025497" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "52." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Should we treat patients with chronic hepatitis C on the waiting list?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Everson GT" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2005.01.010" "Revista" => array:5 [ "tituloSerie" => "J Hepatol" "fecha" => "2005" "volumen" => "42" "paginaInicial" => "447" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15763324" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "53." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiviral therapy in HCV-infected cirrhotics awaiting liver transplantation: a costly strategy for mixed virological results." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Roche B" 1 => "Samuel D" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2009.01.008" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2009" "volumen" => "50" "paginaInicial" => "652" "paginaFinal" => "654" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19231019" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "54." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Peveling-Oberhag J" 1 => "Zeuzem S" 2 => "Hofmann WP" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00430-009-0131-8" "Revista" => array:6 [ "tituloSerie" => "Med Microbiol Immunol" "fecha" => "2010" "volumen" => "199" "paginaInicial" => "1" "paginaFinal" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19902246" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0275" "etiqueta" => "55." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of hepatitis C cirrhosis after liver transplantation." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Firpi RJ" 1 => "Clark V" 2 => "Soldevila-Pico C" 3 => "Morelli G" 4 => "Cabrera R" 5 => "Levy C" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Liver Transplant" "fecha" => "2009" "volumen" => "15" "paginaInicial" => "1063" "paginaFinal" => "1071" ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0280" "etiqueta" => "56." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Preemptive therapy for hepatitis C virus after living-donor liver transplantation." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Sugawara Y" 1 => "Makuuchi M" 2 => "Matsui Y" 3 => "Kishi Y" 4 => "Akamatsu N" 5 => "Kaneko J" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Transplantation" "fecha" => "2004" "volumen" => "78" "paginaInicial" => "1308" "paginaFinal" => "1311" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15548968" "web" => "Medline" ] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0285" "etiqueta" => "57." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Applicability, tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Shergill AK" 1 => "Khalili M" 2 => "Straley S" 3 => "Bollinger K" 4 => "Roberts JP" 5 => "Ascher NA" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-6143.2004.00648.x" "Revista" => array:6 [ "tituloSerie" => "Am J Transplant" "fecha" => "2005" "volumen" => "5" "paginaInicial" => "118" "paginaFinal" => "124" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15636619" "web" => "Medline" ] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0290" "etiqueta" => "58." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Chalasani N" 1 => "Manzarbeitia C" 2 => "Ferenci P" 3 => "Vogel W" 4 => "Fontana RJ" 5 => "Voigt M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20560" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2005" "volumen" => "41" "paginaInicial" => "289" "paginaFinal" => "298" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15660392" "web" => "Medline" ] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0295" "etiqueta" => "59." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peginterferon alpha 2a (40kDa) and rivabirin: comparable rates of sustained virological response in sub-sets of older and younger HCV genotype 1 patients." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "REddy KR" 1 => "Messinger D" 2 => "Popescu M" 3 => "Hadziyannis SJ" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2009.01122.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2009" "volumen" => "16" "paginaInicial" => "724" "paginaFinal" => "731" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19486469" "web" => "Medline" ] ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0300" "etiqueta" => "60." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of disease severity on outcome of antiviral therapy for chonic hepatitis C: lessons from the HALT-C trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Everson GT" 1 => "Hoefs JC" 2 => "Seeff LB" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.21440" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "1675" "paginaFinal" => "1684" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17133499" "web" => "Medline" ] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0305" "etiqueta" => "61." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized trial of pegylated interferon alpha 2b plus ribavirin in the retreatment of chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Jacobson IM" 1 => "Gonzalez SA" 2 => "Ahmed F" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2005.00282.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2005" "volumen" => "100" "paginaInicial" => "2453" "paginaFinal" => "2462" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16279900" "web" => "Medline" ] ] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0310" "etiqueta" => "62." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C y embarazo." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Garcia W" 1 => "Lopez J" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Rev Gastroenterol Peru" "fecha" => "2006" "paginaInicial" => "275" "paginaFinal" => "282" ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0315" "etiqueta" => "63." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pregnancy and esophageal varices." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Britton RC" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Surg" "fecha" => "1982" "volumen" => "143" "numero" => "4" "paginaInicial" => "412" "paginaFinal" => "415" ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0320" "etiqueta" => "64." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pregnancy in liver cirrhosis and/ or portal hypertension." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Cheng Y" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Am J Obst Gynecol" "fecha" => "1977" "volumen" => "128" "paginaInicial" => "812" ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0325" "etiqueta" => "65." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Possible role of high titer maternal viremia in perinatal transmission of hepatitis C virus." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Lin HH" 1 => "Kao JH" 2 => "Hsu HY" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/infdis/169.3.638" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "1994" "volumen" => "169" "paginaInicial" => "638" "paginaFinal" => "641" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8158040" "web" => "Medline" ] ] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0330" "etiqueta" => "66." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mother-to-infant transmission of hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Bernard O" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Gastroenterol Belg" "fecha" => "1998" "volumen" => "61" "paginaInicial" => "192" "paginaFinal" => "194" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9658606" "web" => "Medline" ] ] ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0335" "etiqueta" => "67." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Follow up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women: The role of breast-feeding in transmission." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Ruiz-Extremera A" 1 => "Salmeron J" 2 => "Torres C" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2000" "volumen" => "19" "paginaInicial" => "511" "paginaFinal" => "516" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10877164" "web" => "Medline" ] ] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0340" "etiqueta" => "68." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus. HCV genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Bortolotti F" 1 => "Resti M" 2 => "Marcellini M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2004.053744" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2005" "volumen" => "54" "paginaInicial" => "852" "paginaFinal" => "857" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15888796" "web" => "Medline" ] ] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0345" "etiqueta" => "69." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Italian Observatory for HCV Infection and Hepatitis C in Children. Epidemio-logical profile of 806 Italian Children with hepatitis C virus infection over a 15-year period." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Bortolotti F" 1 => "Jorio R" 2 => "Resti M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2006.12.014" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2007" "volumen" => "46" "paginaInicial" => "783" "paginaFinal" => "790" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17321633" "web" => "Medline" ] ] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0350" "etiqueta" => "70." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic viral hepatitis in children: any role for the pathologist?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Guido M" 1 => "Bortolotti F" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2007.139410" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2008" "volumen" => "57" "paginaInicial" => "873" "paginaFinal" => "877" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18559378" …1 ] ] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0355" "etiqueta" => "71." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Perinatal hepatitis C virus infection: Diagnosis and management." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/adc.2005.081877" "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child" "fecha" => "2006" "volumen" => "91" "paginaInicial" => "781" "paginaFinal" => "785" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0360" "etiqueta" => "72." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha 2a and ribavirin." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1440-1746.2007.04904.x" "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2007" "volumen" => "22" "paginaInicial" => "832" "paginaFinal" => "836" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0365" "etiqueta" => "73." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metabolic syndrome and nonalcoholic fatty liver disease." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2009" "volumen" => "8" "numero" => "1" "paginaInicial" => "S18" "paginaFinal" => "S24" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0370" "etiqueta" => "74." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Los efectos de los acidos grasos no esterificados sobre la matriz extracelular de las células vasculares podrían contribuir a una respuesta aterogénica." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Progreso Médico" "fecha" => "2000" "volumen" => "9" "numero" => "1" "paginaInicial" => "45" "paginaFinal" => "53" ] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0375" "etiqueta" => "75." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD)." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2009" "volumen" => "8" "numero" => "1" "paginaInicial" => "S4" "paginaFinal" => "S8" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0380" "etiqueta" => "76." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Insulin resistance and response to antiviral therapy in chronic hepatitis C: Mechanisms and management." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000282104" "Revista" => array:7 [ "tituloSerie" => "Dig Dis" "fecha" => "2010" "volumen" => "28" "numero" => "1" "paginaInicial" => "285" "paginaFinal" => "293" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317181/v1_201906221034/en/main.assets" "Apartado" => array:4 [ "identificador" => "78188" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/00000009000000S1/v1_201906221034/S1665268119317181/v1_201906221034/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317181?idApp=UINPBA00004N"]

Statistics

Nahum Méndez-Sánchez, Adrian Gadano, Angelo Alves de Mattos, Alejandro Soza, Augusto Marroni Claudio, Marcela Galoppo, David Kershenobich, Edna Strauss, Eduardo Fassio, Gilberto Castañeda, Guillermo Valladares, Henrique Sergio Moraes Coelho, Jorge Daruich, Miguel Garassini, Milagros Dávalos, Misael Uribe, Maribel Rodriguez-Torres, Rodrigo Zapata, Marco Arrese, Francisco Sánchez-Ávila..., Margarita Dehesa, Francisco Bosques Padilla, Paulo Roberto Lerias de Almeida, Mario Pessoa, Rocío Torres-Ibarra, Francisco Hevia, Miguel Contreras, Hugo CheinquerVer más

* Latin American Association for the Study of the Liver (ALEH)

Read

671

Times
was read the article

254

Total PDF

417

Total HTML

Share statistics

 array:24 [
  "pii" => "S1665268119317181"
  "issn" => "16652681"
  "doi" => "10.1016/S1665-2681(19)31718-1"
  "estado" => "S300"
  "fechaPublicacion" => "2010-01-01"
  "aid" => "71380"
  "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
  "copyrightAnyo" => "2010"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Ann Hepatol. 2010;9 Supl 1:S8-S26"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 53
    "formatos" => array:3 [
      "EPUB" => 8
      "HTML" => 17
      "PDF" => 28
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1665268119317193"
    "issn" => "16652681"
    "doi" => "10.1016/S1665-2681(19)31719-3"
    "estado" => "S300"
    "fechaPublicacion" => "2010-01-01"
    "aid" => "71381"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2010;9 Supl 1:S27-9"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 64
      "formatos" => array:3 [
        "EPUB" => 11
        "HTML" => 36
        "PDF" => 17
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "titulo" => "Epidemiology of HCV infection in Latin America"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "S27"
          "paginaFinal" => "S29"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "f0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 531
              "Ancho" => 1002
              "Tamanyo" => 61403
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Prevalence of Hepatitis C infection in Latin American countries&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Nahum M&#233;ndez-S&#225;nchez, Ylse Guti&#233;rrez-Grobe, Ram&#243;n Arturo Kobashi-Marg&#225;in"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Nahum"
              "apellidos" => "M&#233;ndez-S&#225;nchez"
            ]
            1 => array:2 [
              "nombre" => "Ylse"
              "apellidos" => "Guti&#233;rrez-Grobe"
            ]
            2 => array:2 [
              "nombre" => "Ram&#243;n Arturo"
              "apellidos" => "Kobashi-Marg&#225;in"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317193?idApp=UINPBA00004N"
    "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317193/v1_201906221034/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S166526811931717X"
    "issn" => "16652681"
    "doi" => "10.1016/S1665-2681(19)31717-X"
    "estado" => "S300"
    "fechaPublicacion" => "2010-01-01"
    "aid" => "71379"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2010;9 Supl 1:S7"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 96
      "formatos" => array:3 [
        "EPUB" => 14
        "HTML" => 65
        "PDF" => 17
      ]
    ]
    "en" => array:8 [
      "idiomaDefecto" => true
      "titulo" => "The Latin American Association for the Study of the Liver in its Meeting on Diagnosis&#44; Management and Treatment of Hepatitis C"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:1 [
          "paginaInicial" => "S7"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Nahum M&#233;ndez-S&#225;nchez"
          "autores" => array:1 [
            0 => array:3 [
              "preGrado" => "MD&#44; PhD"
              "nombre" => "Nahum"
              "apellidos" => "M&#233;ndez-S&#225;nchez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S166526811931717X?idApp=UINPBA00004N"
    "url" => "/16652681/00000009000000S1/v1_201906221034/S166526811931717X/v1_201906221034/en/main.assets"
  ]
  "en" => array:12 [
    "idiomaDefecto" => true
    "titulo" => "Latin American Association for the Study of the Liver Practice Guidelines"
    "subtitulo" => "Diagnosis&#44; management&#44; and treatment of hepatitis C This document has been approved by the Latin American Association for the Study of the Liver &#40;ALEH&#41;"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "S8"
        "paginaFinal" => "S26"
      ]
    ]
    "autores" => array:1 [
      0 => array:3 [
        "autoresLista" => "Nahum M&#233;ndez-S&#225;nchez, Adrian Gadano, Angelo Alves de Mattos, Alejandro Soza, Augusto Marroni Claudio, Marcela Galoppo, David Kershenobich, Edna Strauss, Eduardo Fassio, Gilberto Casta&#241;eda, Guillermo Valladares, Henrique Sergio Moraes Coelho, Jorge Daruich, Miguel Garassini, Milagros D&#225;valos, Misael Uribe, Maribel Rodriguez-Torres, Rodrigo Zapata, Marco Arrese, Francisco S&#225;nchez-&#193;vila, Margarita Dehesa, Francisco Bosques Padilla, Paulo Roberto Lerias de Almeida, Mario Pessoa, Roc&#237;o Torres-Ibarra, Francisco Hevia, Miguel Contreras, Hugo Cheinquer"
        "autores" => array:28 [
          0 => array:2 [
            "nombre" => "Nahum"
            "apellidos" => "M&#233;ndez-S&#225;nchez"
          ]
          1 => array:2 [
            "nombre" => "Adrian"
            "apellidos" => "Gadano"
          ]
          2 => array:2 [
            "nombre" => "Angelo"
            "apellidos" => "Alves de Mattos"
          ]
          3 => array:2 [
            "nombre" => "Alejandro"
            "apellidos" => "Soza"
          ]
          4 => array:2 [
            "nombre" => "Augusto Marroni"
            "apellidos" => "Claudio"
          ]
          5 => array:2 [
            "nombre" => "Marcela"
            "apellidos" => "Galoppo"
          ]
          6 => array:2 [
            "nombre" => "David"
            "apellidos" => "Kershenobich"
          ]
          7 => array:2 [
            "nombre" => "Edna"
            "apellidos" => "Strauss"
          ]
          8 => array:2 [
            "nombre" => "Eduardo"
            "apellidos" => "Fassio"
          ]
          9 => array:2 [
            "nombre" => "Gilberto"
            "apellidos" => "Casta&#241;eda"
          ]
          10 => array:2 [
            "nombre" => "Guillermo"
            "apellidos" => "Valladares"
          ]
          11 => array:2 [
            "nombre" => "Henrique Sergio Moraes"
            "apellidos" => "Coelho"
          ]
          12 => array:2 [
            "nombre" => "Jorge"
            "apellidos" => "Daruich"
          ]
          13 => array:2 [
            "nombre" => "Miguel"
            "apellidos" => "Garassini"
          ]
          14 => array:2 [
            "nombre" => "Milagros"
            "apellidos" => "D&#225;valos"
          ]
          15 => array:2 [
            "nombre" => "Misael"
            "apellidos" => "Uribe"
          ]
          16 => array:2 [
            "nombre" => "Maribel"
            "apellidos" => "Rodriguez-Torres"
          ]
          17 => array:2 [
            "nombre" => "Rodrigo"
            "apellidos" => "Zapata"
          ]
          18 => array:2 [
            "nombre" => "Marco"
            "apellidos" => "Arrese"
          ]
          19 => array:2 [
            "nombre" => "Francisco"
            "apellidos" => "S&#225;nchez-&#193;vila"
          ]
          20 => array:2 [
            "nombre" => "Margarita"
            "apellidos" => "Dehesa"
          ]
          21 => array:2 [
            "nombre" => "Francisco Bosques"
            "apellidos" => "Padilla"
          ]
          22 => array:2 [
            "nombre" => "Paulo Roberto"
            "apellidos" => "Lerias de Almeida"
          ]
          23 => array:2 [
            "nombre" => "Mario"
            "apellidos" => "Pessoa"
          ]
          24 => array:2 [
            "nombre" => "Roc&#237;o"
            "apellidos" => "Torres-Ibarra"
          ]
          25 => array:2 [
            "nombre" => "Francisco"
            "apellidos" => "Hevia"
          ]
          26 => array:2 [
            "nombre" => "Miguel"
            "apellidos" => "Contreras"
          ]
          27 => array:2 [
            "nombre" => "Hugo"
            "apellidos" => "Cheinquer"
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:3 [
            "entidad" => "Latin American Association for the Study of the Liver &#40;ALEH&#41;"
            "etiqueta" => "&#42;"
            "identificador" => "aff1"
          ]
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Preamble</span><p id="p0170" class="elsevierStylePara elsevierViewall">The following recommendations provide an approach to the establishment of guidelines for the diagnosis&#44; management&#44; and treatment of hepatitis C virus infection&#46; These guidelines are based on a formal analysis and review of recently published literature around the world&#46;</p><p id="p0175" class="elsevierStylePara elsevierViewall">Written for use especially by physicians&#44; the recommendations suggest a range of possibilities for the epidemiology&#44; diagnosis&#44; and Treatment of Hepatitis C infection&#44; but without any intention of establishing standards of care for individual patients&#46; Although we suggest that the recommendations in these guidelines be applied appropriately according to the history of each patient&#44; we emphasize the flexible character &#40;individualization&#41; of these recommendations because they are written as guidelines&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="p0180" class="elsevierStylePara elsevierViewall">Approximately 20 years ago&#44; Houghton&#44; <span class="elsevierStyleItalic">et al&#46;</span>&#44; discovered hepatitis C virus &#40;HCV&#41;&#44; which was established as the main cause of non-A non-B hepatitis&#46; Since then&#44; important advances have been made in the knowledge of the disease&#8217;s biological characteristics and diagnosis and also of its natural history and treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The first consensus conference on hepatitis C was organized in the United States in 1997 and several meetings have since been conducted in order to present and discuss the most important advances in the evolution and management of the infection&#46;</p><p id="p0185" class="elsevierStylePara elsevierViewall">The burden of hepatitis C is of enormous interest because of the natural course of this illness&#44; which can lead to cirrhosis and hepatocellular carcinoma &#40;HCC&#41; after an asymptomatic period that may last for 25 to 30 years&#46; It is important to know the characteristics of the infection&#58; current findings about the progression of the disease suggest that almost 80&#37; of patients convert to a chronic disease&#44; at a high human and economic cost&#46; Recent trend studies predict that HCV-related mortality will continue to increase over coming decades&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="p0190" class="elsevierStylePara elsevierViewall">The main objectives of these guidelines are to make recommendations on diagnosis&#44; to propose preventive actions against infection&#44; and to set up general guidelines on treatment in different risk groups&#46; To establish the quality of evidence that supports the recommendations in these guidelines&#44; a class and level of evidence have been assigned to each recommendation&#44; the former reflecting benefit <span class="elsevierStyleItalic">vs&#46;</span> risk and the latter the strength of the recommendation <a class="elsevierStyleCrossRef" href="#t0005">&#40;Table 1&#41;</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Epidemiology</span><p id="p0195" class="elsevierStylePara elsevierViewall">Several studies have estimated that approximately 180 million people around the world are infected with HCV&#46; In Latin America&#44; the prevalence in the general population is around 1&#46;3&#37;&#44; one of the lowest in the world&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Nevertheless&#44; the prevalence varies between countries and between regions in each country&#46; Regional studies on this topic have estimated prevalence in the general population&#44; and some countries have data regarding various risk groups <a class="elsevierStyleCrossRef" href="#t0010">&#40;Table 2&#41;</a>&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0200" class="elsevierStylePara elsevierViewall">In Mexico&#44; a prevalence lower than 2&#37; has been estimated&#59; Chiquete et al&#44; reported a prevalence between 0&#46;5&#37; and 2&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and Valdespino et al&#44; found a general prevalence of 1&#46;6&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In Brazil&#44; several studies carried out in the general population in different regions of that country have estimated a mean prevalence of 1&#46;32&#37; of HCV&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> General population studies have not been carried out in the Dominican Republic&#44; but data from the Public Health Department estimate a prevalence of 1&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In Puerto Rico&#44; studies carried out in the general population have estimated a prevalence of 2&#46;4&#37;&#59; Perez&#44; <span class="elsevierStyleItalic">et al&#46;</span>&#44; determined that the seroprevalence is similar to that found in the US general population&#44; but concluded that further research is needed in that region&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="p0205" class="elsevierStylePara elsevierViewall">In the Dominican Republic&#44; several studies in risk groups determined a prevalence of 2&#37; in men who have sex with men and a study carried out in the sugarcane fields of the province of Barahona determined a prevalence of 5&#46;3&#37; in this group of working women&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In Costa Rica&#44; studies carried out among voluntary blood donors between 1992 and 2008 estimated a prevalence of 0&#46;3&#37; to 2&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and in Peru&#44; the prevalence among blood donors has been reported to be 0&#46;8&#37; to 1&#46;2&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In Chile&#44; studies carried out in blood donors have estimated a prevalence of around 0&#46;3&#37;&#46; However&#44; the National Health Survey showed a prevalence of 0&#46;12&#37; and studies carried out in Santiago revealed a prevalence of 1&#46;15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0210" class="elsevierStylePara elsevierViewall">Although no large-scale population studies have been carried out in Argentina&#44; several studies according to the National Consensus on hepatitis C estimate a prevalence of about 2&#46;1&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Recommendations</span><p id="p0215" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0025"><li class="elsevierStyleListItem" id="list0170"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Large-scale population studies must be carried out in every Latin American countries to gather better and complete data about the prevalence of hepatitis C in the region <span class="elsevierStyleBold">&#40;Class I&#44; Level C&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Transmission Routes</span><p id="p0225" class="elsevierStylePara elsevierViewall">To assist in creating new methods of control and therapy&#44; it is mandatory to identify the different means of transmission of HCV&#46; HCV can be transmitted by several parenteral routes&#44; of which blood transfusion and intravenous drug use &#40;IVD&#41; are the most common&#46; In developed countries&#44; the main transmission route is the use of intravenous drugs&#44; but in Latin America&#44; several studies show that the main transmission route continues to be transfusion of blood and its derivatives&#46; The frequency of infection by this route has diminished because of the establishment in around 1992 of screening measures in blood banks&#46; However&#44; although current methods for the selection of blood donors and the screening tests are highly developed and the risk of transmission is far lower than 15 years ago&#44; the risk remains&#46; At the same time&#44; intravenous and intranasal drug abuse is increasing in Latin America&#44; making it the second most important route of transmission&#46; According to the current epidemiological model&#44; it is possible that in a few years it will be the main form of transmission&#44; similar to the United States and Europe&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> The use of contaminated needles and paraphernalia is one of the most effective modes of transmission of HCV&#46; Several studies have shown that 65&#37; of infected intravenous drugs users &#40;IVDU&#41; acquire the virus during the first year of drug abuse&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0230" class="elsevierStylePara elsevierViewall">Other potential means of transmission include contact with one or more infected sexual partners&#44; although the prevalence is higher in persons with several partners than in monogamous couples&#46; Even though it is practical to advise HCV carriers that they should inform their partners of their condition&#44; they should be equally informed that the risk of catching the disease is low&#44; as only 1&#37; to 5&#37; of monogamous couples become HCV positive when one of the partners is a carrier&#46; However&#44; the transmission rate increases in persons with multiple sexual partners and persons who have sexual intercourse with prostitutes&#44; anal intercourse&#44; traumatic relations&#44; or intercourse during menses or with inadequate lubrication&#46; Despite the low risk&#44; the use of prophylactic condoms is recommended to nonmonogamous couples&#46; No limitations are recommended on the daily activities of persons with HCV except in the use of razor blades and tooth brushes that should not be shared with other people&#46;</p><p id="p0235" class="elsevierStylePara elsevierViewall">By contrast&#44; vertical transmission occurs in approximately 5&#37; of the children born from an infected mother&#44; with the risk further increased if the mother is also infected with human immunodeficiency virus &#40;HIV&#41;&#46; Nevertheless&#44; there is currently not enough information to recommend a managed form of delivery&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="p0240" class="elsevierStylePara elsevierViewall">Hemodialysis patients have an increased risk of acquiring the infection&#46; The prevalence in hemodialysis patients in Latin America is reported as ranging from 6&#46;7&#37; in Mexico to 71&#37; in Venezuela&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> For healthcare workers&#44; the main risk is through accidental contact with contaminated needles and percutaneous injuries&#44; with the risk of infection being 1&#46;8&#37;&#59; a lower prevalence occurs through contact with exposed mucosa&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Other less common forms of transmission are tattooing and body piercing&#59; because of this&#44; screening is recommended in this high-risk population and in IVDU&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Recommendations</span><p id="p0245" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0030"><li class="elsevierStyleListItem" id="list0175"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Blood donors who have a positive result during screening should be informed in order to prevent transmission <span class="elsevierStyleBold">&#40;Class I&#44; Level C&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0180"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Persons infected with HCV should be counseled with the intention of avoiding transmission to others <span class="elsevierStyleBold">&#40;Class I&#44; Level C&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0185"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0260" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Persons infected with HCV should be counseled with the intention of avoiding donation of blood&#44; organs&#44; other tissues&#44; and semen <span class="elsevierStyleBold">&#40;Class I&#44; Level C&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0190"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p0265" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Viral Hepatitis screening should be mandatory in every blood donor&#46; <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnosis</span><p id="p0270" class="elsevierStylePara elsevierViewall">Because patients with chronic infection generally are asymptomatic&#44; to date the best way to diagnose the infection is screening persons with risk factors and a history of exposure to the virus&#44; in addition to counseling&#46;</p><p id="p0275" class="elsevierStylePara elsevierViewall">Diagnostic tests are classified into serological tests&#44; which identify specific anti-HCV IgG&#44; and molecular tests that identify viral nucleic acid&#46; The initial evaluation is through third-generation immunoenzymatic techniques that identify antibodies against different epitopes of HCV and that have sensitivity and specificity of 97&#37; and 99&#37;&#44; respectively&#46; Also available is the recombinant immunoblot assay &#40;RIBA&#41;&#44; which was originally developed as a more specific test to confirm results from ELISA&#46; However&#44; this is about to fall into disuse because of the usefulness of ELISA&#46; Although HCV antibodies remain detectable lifelong in immunocompetent patients with chronic infection&#44; in patients that recover spontaneously&#44; antibodies tend to disappear within 18 to 20 years&#46; Thus&#44; detection of antibodies indicates contact with the virus only and does not discriminate between acute&#44; chronic&#44; or resolved infection&#46; Interestingly&#44; confirmation of an active HCV infection is performed by demonstrating the presence of HCV-RNA through quantitative detection by RNA amplification methods such as polymerase chain reaction &#40;PCR&#41; or transcription mediated amplification &#40;TMA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> These assays must have a sensitivity of at least 50 IU&#47;mL&#46; Viral RNA can be detected 2 weeks post infection while antibodies are detectable 8 to 12 weeks after contact&#59; therefore&#44; adequate interpretation is required within the different contexts of the test results&#46;</p><p id="p0280" class="elsevierStylePara elsevierViewall">Because of the great genomic variability of HCV&#44; of which six types and more than 90 subtypes are known&#44; genotype determination is useful in epidemiological studies and to identify and predict the possibility of resistance to treatment and the appropriate duration for patient treatment and follow-up&#46;</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Recommendations</span><p id="p0285" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0035"><li class="elsevierStyleListItem" id="list0195"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0290" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Screening in the general population is not recommended <span class="elsevierStyleBold">&#40;Class I&#44; Level C&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0200"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Determination of anti-HCV antibodies is the test of choice for the initial diagnosis in patients with suspected acute or chronic HCV infection <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0205"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0300" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Anti-HCV determination should be done in patients with the following risk factors <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#58;</span></span><ul class="elsevierStyleList" id="li0040"><li class="elsevierStyleListItem" id="list0210"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">a&#41;</span></span><p id="p0305" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">People who received a blood transfusion before 1992&#46;</span></p></li><li class="elsevierStyleListItem" id="list0215"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">b&#41;</span></span><p id="p0310" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Intravenous drug users&#46;</span></p></li><li class="elsevierStyleListItem" id="list0220"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">c&#41;</span></span><p id="p0315" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients in hemodialysis&#46;</span></p></li><li class="elsevierStyleListItem" id="list0225"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">d&#41;</span></span><p id="p0320" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with elevated aminotransferases&#46;</span></p></li><li class="elsevierStyleListItem" id="list0230"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">e&#41;</span></span><p id="p0325" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Healthcare workers exposed to infected blood&#46;</span></p></li><li class="elsevierStyleListItem" id="list0235"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">f&#41;</span></span><p id="p0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with hemophilia who received clotting factor concentrates before 1987&#46;</span></p></li><li class="elsevierStyleListItem" id="list0240"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">g&#41;</span></span><p id="p0335" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Children born to mothers infected with HCV&#46;</span></p></li><li class="elsevierStyleListItem" id="list0245"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">h&#41;</span></span><p id="p0340" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Sexual partners of hepatitis C patients&#46;</span></p></li><li class="elsevierStyleListItem" id="list0250"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">i&#41;</span></span><p id="p0345" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">HIV infected patients&#46;</span></p></li></ul></p></li><li class="elsevierStyleListItem" id="list0255"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p0350" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Viral RNA analysis should be done in&#58;</span><ul class="elsevierStyleList" id="li0045"><li class="elsevierStyleListItem" id="list0260"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">a&#41;</span></span><p id="p0355" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients positive for anti-HCV antibodies <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0265"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">b&#41;</span></span><p id="p0360" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients in whom antiviral treatment is considered <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0270"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">c&#41;</span></span><p id="p0365" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Immunosuppressed patients with unexplained chronic elevation of aminotransferase levels&#46; <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li></ul></p></li></ul></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Utility of Liver Biopsy in Chronic Infection</span><p id="p0370" class="elsevierStylePara elsevierViewall">Liver biopsy is a procedure indicated in a broad spectrum of diseases&#46; The basic requirements for its use are the benefits that it will bring to the patient&#44; as well as the impossibility of obtaining the same detailed information with any other procedure&#46; Possible benefits include identification of liver status&#44; identification of useful characteristics at the time of treatment decisions&#44; or monitoring of the advance of fibrosis or cirrhosis that needs surveillance for HCC&#46; However&#44; the use of this diagnostic procedure in chronic HCV has been questioned in recent years&#46; In addition&#44; the act of soliciting a biopsy can be a challenge because of its invasiveness and because patients correlate the procedure with malignancy&#46; However&#44; advances in surgical techniques and the control of hemorrhage in the second half of last century have diminished complications during this procedure&#46; Liver biopsy continues to be the preferred method to allow evaluation of the grade and stage of hepatic lesions&#46; Patients with confirmed serology for Hepatitis C and clinical and&#47;or laboratorial data for other associated diseases&#44; as auto-immune or metabolic disorders&#44; certainly deserve liver biopsy for differential diagnosis</p><p id="p0375" class="elsevierStylePara elsevierViewall">Although liver biopsy has been established as the &#8220;gold standard&#8221; in the diagnosis of chronic hepatitis C&#44; it is not without contraindications and complications&#46; The main contraindications to biopsy are alterations in coagulation and tense ascites&#46; A prolonged prothrombin time and a low platelet count are major risk factors for bleeding&#46; In addition&#44; because of the possible subjectivity of histological description and interpretation&#44; numeric systems have been proposed to make classification of necrosis&#44; inflammation&#44; and fibrosis less subjective <a class="elsevierStyleCrossRef" href="#t0015">&#40;Table 3&#41;</a>&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Recommendations</span><p id="p0380" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0050"><li class="elsevierStyleListItem" id="list0275"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0385" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Liver biopsy is essential in those patients with hepatitis C in whom more information is required about the stage of fibrosis and&#47;or grade of peri-portal or lobular inflammation&#44; for prognostic purposes <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0280"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0390" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">For patients with presumed associated conditions&#44; as auto-immune or metabolic disorders&#44; a liver biopsy can effectively make a differential diagnosis <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Use of Noninvasive Methods to Evaluate The Stage of Liver Fibrosis</span><p id="p0395" class="elsevierStylePara elsevierViewall">Although liver biopsy is considered the &#8220;gold standard&#8221; for the diagnosis of hepatic fibrosis&#44; because of its complications and technical difficulty&#44; noninvasive methods have been developed for the evaluation of fibrosis&#46; However&#44; such methods are most effective for the early stages of disease with little fibrosis or cirrhosis&#44; leaving the intermediate stages without a reliable diagnostic method&#46; One of the new methods is transient elastography&#59; this method has not fulfilled all the criteria necessary to replace hepatic biopsy but has proven its efficacy in the diagnosis of fibrosis extension when combined with other noninvasive methods&#46;</p><p id="p0400" class="elsevierStylePara elsevierViewall">Recently&#44; noninvasive methods such as transient elastography and FibroTest &#174; have been studied in patients with persistently normal alanine transaminase &#40;ALT&#41; levels&#46; The results show that transient elastography might be very useful in the selection of patients with significant fibrosis for antiviral therapy&#44; and eventually remove the need for taking a liver biopsy&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Indications and Contraindications for the Treatment of Hcv Infection</span><p id="p0405" class="elsevierStylePara elsevierViewall">Evidence shows that 55&#37; to 85&#37; of HCV-infected patients will remain infected through their lifetime&#46; The risk of developing cirrhosis rises from 5&#37; to 25&#37; over a period of 30 years&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Prior to treatment&#44; it is necessary to know the stage of liver disease&#44; to determine the presence of compensated or decompensated cirrhosis or portal hypertension&#44; and to know factors such as age&#44; comorbidities&#44; extrahepatic manifestations such as cryoglobulinemia and glomerulonephritis&#44; and quality of life&#46;</p><p id="p0410" class="elsevierStylePara elsevierViewall">Consensus indicates that treatment should be with a combination of pegylated interferon and ribavirin&#46; Medical treatment is indicated in patients who are anti-HCV positive and HCV-RNA positive and in whom histological evidence indicates chronic hepatitis&#46;</p><p id="p0415" class="elsevierStylePara elsevierViewall">The goal of treatment is to prevent complications and death related to HCV infection&#46; Because of the chronic evolution of the disease&#44; the response is determined by several biochemical&#44; virological&#44; or histological variables including normalization of ALT levels&#44; absence of viral RNA on PCR&#44; or improvement of at least two points on the scale of necroinflammation or fibrosis scores&#46;</p><p id="p0420" class="elsevierStylePara elsevierViewall">Current recommendations to treat chronic HCV-infected patients have been suggested from randomized clinical trials&#46; Characteristics of patients in whom therapy is accepted are shown in <a class="elsevierStyleCrossRef" href="#t0020">Table 4</a>&#44; and characteristics of patients in whom therapy is contraindicated are shown in <a class="elsevierStyleCrossRef" href="#t0025">Table 5</a>&#46;</p><elsevierMultimedia ident="t0020"></elsevierMultimedia><elsevierMultimedia ident="t0025"></elsevierMultimedia><p id="p0425" class="elsevierStylePara elsevierViewall">Patients with HCV genotype 2 or 3 may be treated in any stage of the disease because of the elevated frequency of sustained virological response &#40;SVR&#41; in those groups&#46;</p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Recommendations</span><p id="p0430" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0055"><li class="elsevierStyleListItem" id="list0285"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0435" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The decision to establish therapy for any patient has to be individualized&#44; with awareness of the severity of liver damage&#44; the probability of response to treatment&#44; the potential for severe adverse effects&#44; and the presence of comorbidities <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0290"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0440" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The ideal patients to treat are those with chronic hepatitis C&#44; with genotype 2 and 3 and low viral load and those who have Child A liver cirrhosis associated with &#62; 75&#44;000 platelets&#47;ml and hemoglobin &#62; 12 g&#47;dL <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0295"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0445" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Combined treatment with pegylated interferon and ribavirin is contraindicated in patients with&#58;</span><ul class="elsevierStyleList" id="li0060"><li class="elsevierStyleListItem" id="list0300"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">a&#41;</span></span><p id="p0450" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Decompensated psychiatric disease&#46;</span></p></li><li class="elsevierStyleListItem" id="list0305"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">b&#41;</span></span><p id="p0455" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Decompensated diabetes mellitus&#46;</span></p></li><li class="elsevierStyleListItem" id="list0310"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">c&#41;</span></span><p id="p0460" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Decompensated arterial hypertension&#46;</span></p></li><li class="elsevierStyleListItem" id="list0315"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">d&#41;</span></span><p id="p0465" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Decompensated hemoglobinopathy&#46;</span></p></li><li class="elsevierStyleListItem" id="list0320"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">e&#41;</span></span><p id="p0470" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Autoimmune disease with the exception of treated autoimmune thyroid disease&#46;</span></p></li><li class="elsevierStyleListItem" id="list0325"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">f&#41;</span></span><p id="p0475" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Immunosuppressive treatment&#46;</span></p></li><li class="elsevierStyleListItem" id="list0330"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">g&#41;</span></span><p id="p0480" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Thrombocytopenia &#60; 50&#44;000 platelets&#47;mL&#46;</span></p></li><li class="elsevierStyleListItem" id="list0335"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">h&#41;</span></span><p id="p0485" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Neutropenia &#60; 750 cells&#47;mL&#46;</span></p></li><li class="elsevierStyleListItem" id="list0340"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">i&#41;</span></span><p id="p0490" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Hemoglobin &#60; 12g&#47;dL&#46; <span class="elsevierStyleBold">&#40;Class II&#44; Level A&#41;&#46;</span></span></p></li></ul></p></li></ul></p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Predictive Factors for the Response to Treatment</span><p id="p0495" class="elsevierStylePara elsevierViewall">During treatment&#44; several types of virological response may occur&#44; the most important of which is the SVR&#44; which is defined as the absence of detectable serum viral RNA by PCR assay for 24 weeks after suspension of treatment&#46; Knowledge prior to treatment of the factors predictive of treatment response is useful to predict SVR&#46; The combination of pegylated interferon with ribavirin has an SVR in 50&#37; to 80&#37; of patients&#46; However&#44; this rate is still low considering the adverse effects&#44; costs&#44; and duration of treatment&#46;</p><p id="p0500" class="elsevierStylePara elsevierViewall">It is possible to predict SVR before the beginning of treatment if several characteristics of the virus or of the host are known&#44; such as viral genotype &#40;1 <span class="elsevierStyleItalic">vs&#46;</span> non-1&#41;&#44; pretreatment viral load&#44; fibrosis stage&#44; gamma-glutamyl transpeptidase &#40;GGTP&#41;&#44; age&#44; race&#44; weight&#44; and insulin resistance&#46; Other predictive factors might be identified after initiating treatment&#44; such as the rapid viral response &#40;RVR&#59; viral RNA not detectable by the fourth week of treatment&#41; and the early viral response &#40;EVR&#59; a reduction of at least 2 log in viral load by the 12th week or a negative HCV-PCR&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In patients with HCV genotype 1&#44; the rate of response to treatment based on pegylated interferon and ribavirin is 40&#37;&#44; whereas in patients with genotype 2 or 3 it is around 80&#37;&#46;</p><p id="p0505" class="elsevierStylePara elsevierViewall">Another important factor is coinfection with other viruses&#44; because a lower rate of response to treatment has been observed in patients coinfected with hepatitis B virus &#40;HBV&#41;&#46; In HIV-coinfected patients&#44; development of fibrosis is faster and the progression to liver failure and hepatocellular carcinoma occurs earlier&#44; but response rates are similar to those of patients without HIV coinfection&#46;</p><p id="p0510" class="elsevierStylePara elsevierViewall">Patients with hepatitis C and cirrhosis have lower rates of sustained response&#46; Even when cirrhosis is absent&#44; the probability of response to treatment diminishes as the stage of fibrosis increases&#46; In addition&#44; treatment compliance has been demonstrated to be a fundamental factor in treatment effectiveness&#44; so that every effort must be made to ensure the patient maintains the dose and duration of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="p0515" class="elsevierStylePara elsevierViewall">However&#44; and despite the inadequate predictive factors for response&#44; it is possible that in the near future&#44; new techniques will be developed&#46; These could include the identification of individual genetic polymorphisms such as the one found near the IL-28B gene encoding interferon &#947;3 that is associated with an approximately twofold change in response to treatment<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and profiles of protein expression that will open up a new world of possibilities to better identify good and bad responders to HCV therapy&#46; It is considered that complete remission of the infection has occurred when there is no detectable viral load of HCV 6 months after the completion of a course of treatment&#46;</p><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Recommendations</span><p id="p0520" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0065"><li class="elsevierStyleListItem" id="list0345"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0525" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The major pre-treatment predictive factors for treatment response are viral load&#44; viral genotype&#44; and fibrosis stage&#46; Recently RVR has been appointed as the most important predictive factor of SVR&#46; <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0350"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0530" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The principal negative predictive factor is a detectable viral load or a reduction of less than 2 logs by the 12<span class="elsevierStyleSup">th</span> week of treatment <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Hepatitis C Treatment in Na&#239;ve Patients</span><p id="p0535" class="elsevierStylePara elsevierViewall">The selection of candidate patients to receive treatment should take into consideration several factors including&#58; the probability of response&#44; the likelihood for adverse effects&#44; cost&#44; and effectiveness of treatment&#46;</p><p id="p0540" class="elsevierStylePara elsevierViewall">The aim of therapy is to prevent long-term complications and death caused by this disease&#46; In the short term&#44; SVR&#44; normalization of ALT levels &#40;if abnormal&#41;&#44; and histological improvement are more important&#46; This is achieved with viral eradication&#44; which is defined as undetectable viral RNA 6 months after finishing therapy &#40;SVR&#41;&#46; All HCV-infected people are potentially treatable unless contraindications exist&#46;</p><p id="p0545" class="elsevierStylePara elsevierViewall">The therapeutic regimens depend on the type of interferon and the viral genotype&#46; It has been confirmed by several studies that treatment should include a combination of pegylated interferon plus ribavirin because of its greater efficacy compared with monotherapy of interferon and with the combination of standard interferon plus ribavirin&#46; A meta-analysis recently published comparing both types of pegylated interferons showed a trend toward higher SVR rates with peginterferon alpha 2a &#40;47&#37;&#41; compared with peginterferon alpha 2b &#40;41&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Treatment must also be strictly supervised by experts in order to document its effectiveness and safety&#46;</p><p id="p0550" class="elsevierStylePara elsevierViewall">Patients with HCV genotype 1 are considered difficult to cure because the SVR rate is considerably lower in this group of patients than in patients with non-1 genotype HCV&#46; For this reason&#44; several studies have been carried out that demonstrate that treatment with pegylated interferon and ribavirin at higher doses for a period of 48 weeks may obtain a greater rate of SVR&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="p0555" class="elsevierStylePara elsevierViewall">For patients with HCV genotype 2 or 3&#44; it has been established that treatment should be for 24 weeks with a combination of pegylated interferon plus ribavirin&#44; which shows an effectiveness around 80&#37;&#8211;90&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> However&#44; patients with genotypes 2 or 3 who do not show a RVR have a rather low SVR&#46; In this setting&#44; an extension of treatment duration to 36&#8211;48 weeks might be considered&#46;</p><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Recommendations</span><p id="p0560" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0070"><li class="elsevierStyleListItem" id="list0355"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0565" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Virological response to treatment must be monitored at the 4th&#44; 12th&#44; and 24th weeks of treatment and at the 24th week after treatment is finished&#44; always with the same method <span class="elsevierStyleBold">&#40;Class II&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0360"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0570" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment of patients with HCV genotype 1 must be for 48 weeks with pegylated interferon alpha 2b 1&#46;5 mg&#47;kg&#47;week s&#46;c&#46; or pegylated interferon alpha 2a 180 mg&#47;kg&#47;week s&#46;c&#46; combined with weight dosed ribavirin 800&#8211;1400 mg&#47;day &#40;weight-based dose&#41;</span><a class="elsevierStyleCrossRef" href="#t0030">&#40;Table 6&#41;</a><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p><elsevierMultimedia ident="t0030"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="list0365"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0575" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with HCV genotype 1 with factors predictive of good response and RVR may be treated for 24 weeks <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0370"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p0580" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In slow-responder patients&#44; a treatment for 72 weeks should be considered <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0375"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">5&#46;</span></span><p id="p0585" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients who do not achieve EVR and those that present with detectable viral RNA at 24 weeks&#44; treatment ought to be suspended <span class="elsevierStyleBold">&#40;Class II&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0380"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">6&#46;</span></span><p id="p0590" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with HCV genotype 2 or 3 must be treated with pegylated interferon plus ribavirin for 24 weeks <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0385"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">7&#46;</span></span><p id="p0595" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment of patients with HCV genotype 2 or 3 with factors predictive of a good response may be shortened to 16 weeks <span class="elsevierStyleBold">&#40;Class II&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0390"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">8&#46;</span></span><p id="p0600" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment of patients with HCV genotype 2 or 3 with bad or slow virological response may be prolonged to 36&#8211;48 weeks <span class="elsevierStyleBold">&#40;Class II&#44; Level A&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Approach and Management of Patients With Normal Levels of Transaminases</span><p id="p0605" class="elsevierStylePara elsevierViewall">Approximately 30&#37; of patients with chronic hepatitis C have persistently normal ALT &#40;PNALT&#41; values&#46; Most of these patients have mild or moderate inflammation and absent or mild fibrosis&#44; which can progress over time determining cirrhosis or hepatocellular carcinoma might be found&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><p id="p0610" class="elsevierStylePara elsevierViewall">AST and ALT elevations normally act as important markers of liver injury&#46; However&#44; the definition of &#8220;normal values&#8221; is currently subjective because reference ranges vary between laboratories&#44; with values above 40 U&#47;L considered high normal levels&#46; There are also differences between males and females&#58; recent data show that in the healthy population the upper level of normal ALT should be around 30 U&#47;L for men and around 19 U&#47;L for women&#46; Application of these limits would improve the sensitivity of the test for detecting patients with asymptomatic disease&#44; although the specificity would diminish&#46; The definition of PNALT in patients with chronic hepatitis C varies in the literature&#44; but most authors define it as ALT measurements lower than 40 U&#47;L on two or three different occasions separated by at least 1 month in a period of 6 months&#46; Most PNALT patients are women&#59; nearly 50&#37; have a genotype 1 virus and viral RNA titers are significantly lower than in patients with elevated ALT&#46; Although hepatic damage is generally mild and stable over time in patients with PNALT and they maintain a good prognosis&#44; almost 20&#37; to 30&#37; of these patients progress to fibrosis&#44; which is why they have recently been considered ade-quate candidates for antiviral therapy&#46;</p><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Recommendations</span><p id="p0615" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0075"><li class="elsevierStyleListItem" id="list0395"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0620" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The indications for treatment must be evaluated independently of ALT activity <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0400"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0625" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment protocols in patients with PNALT must be the same as that used in patients with elevated ALT&#46; Likewise&#44; the SVR to combined treatment is similar to that observed in patients with elevated ALT <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0405"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0630" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">As in other patients&#44; treatment must be individualized and adverse effects&#44; comorbidities&#44; likelihood for therapy response&#44; the viral genotype&#44; and the severity of illness assessed by liver biopsy must be considered before treatment commences <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0410"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p0635" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In PNALT patients in which antiviral treatment is not initiated due to minimal liver disease&#44; ALT levels must be monitored every 6 to 12 months and the possibility of taking serial liver biopsies to evaluate the progression of the disease should be offered to reconsider antiviral therapy <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Treatment in Cirrhotic Patients</span><p id="p0640" class="elsevierStylePara elsevierViewall">The main objectives of treatment in cirrhotic patients are to prevent disease complications&#44; allow regression of fibrosis&#44; and avoid reinfection of the graft in those patients who will receive a liver transplantation&#46;</p><p id="p0645" class="elsevierStylePara elsevierViewall">When SVR is evaluated in cirrhotic patients&#44; especially in those with decompensated disease&#44; we observe that it is lower than in those patients with chronic hepatitis without cirrhosis&#46; It has also been described that cirrhotic patients present a higher probability of having treatment complications&#46;</p><p id="p0650" class="elsevierStylePara elsevierViewall">Of patients with Child A cirrhosis&#44; it is reported that almost 30&#37; to 40&#37; have SVR&#59; and patients who do not have SVR have a higher probability of developing HCC and a higher mortality rate&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a></p><p id="p0655" class="elsevierStylePara elsevierViewall">With respect to treatment benefits&#44; from an evaluation of studies carried out in patients with cirrhosis&#44; we conclude that the SVR is inferior and that the evidence level for treatment success is lower for decompensated cirrhotic patients because of the small response and increased probability of developing complications&#46;</p><p id="p0660" class="elsevierStylePara elsevierViewall">Treatment with pegylated interferon plus ribavirin is clearly indicated in patients with compensated cirrhosis&#44; with the condition that their levels of white cells and platelets allow them to tolerate the decrease induced by the treatment&#46; The therapy may be contraindicated in advanced cirrhotic patients with Child B and C class liver disease&#44; due to possibility of decompensation and death&#46;</p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Recommendations</span><p id="p0665" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0080"><li class="elsevierStyleListItem" id="list0415"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0670" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with compensated Child A cirrhosis must be referred for evaluation and must receive the usual treatment <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0420"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0675" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with Child B cirrhosis awaiting transplantation must be treated if the virus is genotype 2&#59; patients with Child B and C liver disease should be treated after compensation <span class="elsevierStyleBold">&#40;Class II&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0425"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0680" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with decompensated Child B and C liver disease should be referred to a transplantation unit for evaluation <span class="elsevierStyleBold">&#40;Class I&#44; level A&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Treatment in Posttransplantation Patients</span><p id="p0685" class="elsevierStylePara elsevierViewall">Liver transplantation offers an effective treatment that significantly reduces morbidity and mortality among these patients&#46; However&#44; hepatic graft reinfection is universal in posttransplantation patients because of the advanced liver disease related to HCV&#46; Reinfection is almost inevitable in patients with measurable viral RNA subjected to liver transplantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">45</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> The natural history of hepatitis C is more aggressive after liver transplantation than in immunocompetent patients&#46; Graft cirrhosis has been reported in almost 30&#37; of patients five years after liver transplantation and the survival rate is significantly lower than that in HCV-negative patients&#46;</p><p id="p0690" class="elsevierStylePara elsevierViewall">The aim of antiviral therapy prior to transplantation is to reach an SVR at the moment of transplantation and clearance of viral RNA to prevent recurrence and stop disease progression&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">50</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><p id="p0695" class="elsevierStylePara elsevierViewall">A preventive strategy seems attractive because treatment is begun while viral levels remain low and before the graft is damaged and thus would be expected to reach higher SVR rates&#46; Nevertheless&#44; in practice only 40&#37; to 60&#37; of patients are candidates to receive treatment in view of the fact that these patients receive high doses of immunosuppression with its consequent pancytopenia&#44; mild renal dysfunction&#44; and the presence of additional medical conditions during the early posttransplantation phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">48</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">53</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> Monotherapy with interferon or peginterferon is not recommended because of low rates of SVR&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> Peginterferon combined with ribavirin gives higher response rates&#44; but is not well tolerated in patients in the early posttransplantation phase&#44; so the doses need to be reduced in the majority of cases&#46;</p><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Recommendations</span><p id="p0700" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0085"><li class="elsevierStyleListItem" id="list0430"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0705" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment of HCV in patients who receive a liver transplantation is indicated only in candidate patients with adequate supervision of therapy administration and of adverse effects <span class="elsevierStyleBold">&#40;Class IIA&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0435"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0710" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The therapeutic regime of choice in posttransplantation patients should be peginterferon with ribavirin <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0440"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0715" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Posttransplantation patients should receive erythropoietin and granulocyte growth factor so that the ribavirin dosage does not need to be reduced <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Treatment in Nonresponders and Relapsers</span><p id="p0720" class="elsevierStylePara elsevierViewall">It is considered that almost 60&#37; of patients treated with standard interferon and ribavirin do not respond to treatment&#46; The numbers are even more concerning for the genotype 1 subgroup&#44; as 60&#37; to 75&#37; of these patients will not respond to therapy&#44; while in the genotype 2 and 3 group of patients&#44; almost 30&#37; to 40&#37; will not respond&#46; The response to therapy with pegylated interferon plus ribavirin varies according to the viral genotype&#58; it has been found that patients with genotype 1a have an SVR rate of 42&#37; to 52&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> whereas patients with genotype 2 or 3 have an SVR rate of 76&#37; to 84&#37;&#46; If the viral load does not diminish by 2 logs by the 12th week of treatment&#44; the patient is considered a nonresponder&#46; If the viral load is undetectable at the end of treatment but reappears 6&#8211;12 months after the treatment&#44; the patient is considered a relapser&#46;</p><p id="p0725" class="elsevierStylePara elsevierViewall">In nonresponding patients&#44; retreatment with the same therapeutic regime reaches an SVR of less than 5&#37;&#44; so is not recommended&#46; Furthermore&#44; modification of therapy with alternative interferons does not demonstrate sufficient evidence of success&#46;</p><p id="p0730" class="elsevierStylePara elsevierViewall">Although it is probable that patients who relapse will respond to the same treatment as given the first time&#44; it is very probable that they will relapse again&#46; In these patients that relapse&#44; the following therapeutic regimes have been proven effective&#58; pegylated interferon alpha-2b 1&#46;5 mg&#47;kg&#47;week plus ribavirin 800 mg daily&#44; and pegylated interferon 1 mg&#47;kg&#47;week plus ribavirin 1&#44;000 to 2&#44;000 mg a day&#46; However&#44; the SVR is 50&#37; with the former therapy and 32&#37; with the latter&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a></p><p id="p0735" class="elsevierStylePara elsevierViewall">In a study carried out by Reddy&#44; <span class="elsevierStyleItalic">et al&#46;</span>&#44; patients received pegylated interferon alpha 2a 180 pg per week plus ribavirin 1&#44;000 to 2&#44;000 mg a day for 48 weeks&#59; higher relapse rates were seen in patients over 50 years &#40;SVR 39&#37;&#41; than in younger patients &#40;SVR 52&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> Everson and colleagues also described that another predictive factor for a poor prognosis is advanced fibrosis level and cirrhosis&#46; In non responder patients re-treated with pegylated interferon alpha 2a the authors found that a significant reduction in SVR rates occurred as disease severity increased&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a></p><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Recommendations</span><p id="p0740" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0090"><li class="elsevierStyleListItem" id="list0445"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0745" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Retreatment with pegylated interferon plus ribavirin in nonresponders and relapsers should be individualized&#46; Treatment should be stopped if HCV RNA is detectable at 12 weeks at any level&#46; <span class="elsevierStyleBold">&#40;Class II&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0450"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0750" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Retreatment with pegylated interferon plus ribavirin in nonresponders and relapsers to a previous course of standard interferon plus ribavirin or interferon monotherapy may be intended&#46; <span class="elsevierStyleBold">&#40;Class II&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0455"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0755" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The next patients are considerate good candidates for re treatment&#58;</span><ul class="elsevierStyleList" id="li0095"><li class="elsevierStyleListItem" id="list0460"><span class="elsevierStyleLabel">&#176;</span><p id="p0760" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Prior relapse &#40;vs non-response&#41;</span></p></li><li class="elsevierStyleListItem" id="list0465"><span class="elsevierStyleLabel">&#176;</span><p id="p0765" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Prior non-adherence &#40;if correctable&#41;</span></p></li><li class="elsevierStyleListItem" id="list0470"><span class="elsevierStyleLabel">&#176;</span><p id="p0770" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Previous monotherapy &#40;vs IFN&#47;RBV&#41;</span></p></li><li class="elsevierStyleListItem" id="list0475"><span class="elsevierStyleLabel">&#176;</span><p id="p0775" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">No cirrhosis</span></p></li><li class="elsevierStyleListItem" id="list0480"><span class="elsevierStyleLabel">&#176;</span><p id="p0780" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Genotype 2&#8211;3 with low viral load <span class="elsevierStyleBold">&#40;Class II&#44; Level B&#41;&#46;</span></span></p></li></ul></p></li><li class="elsevierStyleListItem" id="list0485"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p0785" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">These patients should be monitored frequently and the therapeutic trial should be intended for at least 12 weeks&#46; <span class="elsevierStyleBold">&#40;Class II&#44; Level B&#41;</span>&#46;</span></p></li></ul></p></span></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Management of Hcv Infection in Pregnant Women</span><p id="p0790" class="elsevierStylePara elsevierViewall">The prevalence of anti-HCV antibodies in pregnant women is similar to that in the general population&#44; and tends to increase in pregnant women with significant risk factors such as IVDU and HIV coinfection&#46; In the absence of cirrhosis and portal hypertension&#44; pregnant women infected with HCV do not have obstetric complications&#44; although there are reports of prematurity&#44; low birth weight&#44; and microcephaly&#46; It is infrequent that women with cirrhosis become pregnant&#46; However&#44; if they do&#44; special care is required because of the possibility of decompensation and worsening of the portal hypertension secondary to the increase in abdominal pressure and in the plasma volume and the secondary coagulopathy that may induce severe hemorrhage during delivery&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">61</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a><a class="elsevierStyleCrossRef" href="#t0035">Table 7</a> shows the indications for screening in pregnant women&#46;</p><elsevierMultimedia ident="t0035"></elsevierMultimedia><p id="p0795" class="elsevierStylePara elsevierViewall">Several studies have shown no evidence that the type of birth influences perinatal transmission&#46; Likewise&#44; several studies performed on breast-feeding indicate that even though small quantities of HCV are found in breast milk and colostrum&#44; these levels are not sufficient to transmit infection because the virus may be inactivated by gastric juices and the immunological compounds of breast milk&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">64</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a></p><p id="p0800" class="elsevierStylePara elsevierViewall">Treatment based on pegylated interferon and ribavirin is contraindicated because of the elevated teratogenicity of the ribavirin and the neurotoxic effect of interferon&#46; Antiviral treatment is not recommended during pregnancy&#46;</p><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Recommendations</span><p id="p0805" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0100"><li class="elsevierStyleListItem" id="list0490"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0810" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Every HCV-infected patient must be counseled to avoid alcohol and to prevent hepatotoxic drug use including medicinal herbs <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0495"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0815" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients who have not been immunized against hepatitis A and B must be vaccinated against these viruses <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0500"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0820" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pregnant women with premature membrane rupture over 6 hours or vaginal rupture may receive treatment in order to avoid vertical transmission <span class="elsevierStyleBold">&#40;Class II&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Management of Hcv Infection in Children</span><p id="p0825" class="elsevierStylePara elsevierViewall">The global prevalence of hepatitis C among children is very low&#44; about 1&#37;&#44; so little is known about this disease&#46; The risk groups correspond principally to children with hematological disorders who received transfusions before 1992&#44; and vertical transmission represents one of the most important routes of transmission&#46; Screening of anti-HCV in children of HCV-infected mothers must be performed after 18 months of age because of the high rate of antibodies transmitted from the mother within the first months after birth&#46; However&#44; if an early diagnosis of HCV infection is desired&#44; testing for serum HCV RNA may be performed at 1&#8211;2 months of age&#46;</p><p id="p0830" class="elsevierStylePara elsevierViewall">Most infected children&#44; regardless of the age at which infection was acquired&#44; become chronically ill&#46; Spontaneous resolution in children seems to be infrequent&#44; although the highest frequency occurs in patients infected with genotype 3&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">67</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a> In children&#44; the disease is classically asymptomatic and characterized by a benign course for approximately two decades&#46; Advanced liver disease is extremely rare among pediatric patients&#46; Because of the slow progress of the disease&#44; children are ideal patients for treatment with the goals of viral clearance&#44; regression or retardation of fibrosis onset&#44; prevention of chronic disease and the development of HCC&#44; and improvement of quality of life&#46; Treatment is considered for patients aged 3&#8211;18 years&#44; and studies performed so far support the efficacy of combined treatment with pegylated interferon alpha 2a at doses of 100 mg&#47;m<span class="elsevierStyleSup">2</span>&#47;week or pegylated interferon alpha 2b at doses of 60 mg&#47;m<span class="elsevierStyleSup">2</span>&#47;week or 1&#46;5 mg&#47;kg&#47;week plus ribavirin at doses of 15 mg&#47;kg&#47;day for 48 weeks&#46;</p><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Recommendations</span><p id="p0835" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0105"><li class="elsevierStyleListItem" id="list0505"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0840" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Diagnosis of HCV in children is performed by the same methods as in adults <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0510"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0845" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment can be started from the age of 3 years with the same indications as in adults <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0515"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0850" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Screening for anti-HCV must be considered at 18 months in children born to HCV-infected mothers <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span> Testing for HCV RNA may be performed at 1&#8211;2 months of age if an earlier diagnosis is desired&#46;</span></p></li><li class="elsevierStyleListItem" id="list0520"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p0855" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment is based on combined pegylated interferon alpha 2a at doses of 100 mg&#47;m<span class="elsevierStyleSup">2</span>&#47;week or alpha 2b at doses of 60 mg&#47;m<span class="elsevierStyleSup">2</span>&#47;week or 1&#8211;1&#46;5 mg&#47;kg&#47;week plus ribavirin at doses of 15 mg&#47;kg&#47;day for 48 weeks <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Treatment of HCV-Infected Patients with Kidney Disease</span><p id="p0860" class="elsevierStylePara elsevierViewall">Patients with kidney disease may be infected by HCV through hemodialysis &#40;due to contaminated blood&#44; the absence or inadequate disinfection of medical equipment&#44; or sharing vials of heparin&#41;</p><p id="p0865" class="elsevierStylePara elsevierViewall">It has been demonstrated that in HCV-infected patients with kidney dysfunction under treatment with hemodialysis&#44; mortality increases because of progression of the liver damage &#40;cirrhosis and HCC&#41;&#46; In addition&#44; individual and transplanted organ survival rates decrease after kidney transplantation&#46;</p><p id="p0870" class="elsevierStylePara elsevierViewall">By contrast&#44; it has been noted that levels of ALT in individuals with chronic kidney failure are only slightly elevated or even normal despite the advanced hepatic damage&#46; Thus&#44; hepatic biopsy is recommended in these patients in order to determine the stage of the hepatic lesion following the same guidelines for the procedure in patients without renal dysfunction&#46; Even though patients with renal disease have a major platelet dysfunction that may favor hemorrhagic states&#44; complications are rarely reported in hemodialyzed patients who undergo hepatic biopsy&#46;</p><p id="p0875" class="elsevierStylePara elsevierViewall">Anti-HCV measurement and HCV-RNA quantification should be completed in all patients before initiation of hemodialysis and before and after kidney transplantation&#46; Likewise&#44; screening must be performed in hemodialyzed patients who present with any spontaneous or unexplained liver damage and in people who suffer a nosocomial exposure to HCV&#46;</p><p id="p0880" class="elsevierStylePara elsevierViewall">The suggested treatment continues to be peginterferon plus ribavirin&#44; even in hemodialyzed patients&#46; However&#44; the grade of kidney dysfunction must be taken into account because both drugs are filtered by the kidney&#46; Ribavirin increases the risk of hemolytic anemia and cannot be removed by hemodialysis&#44; so a lower dose and caution in its administration or even avoiding the administration are recommended when the creatinine clearance is &#60; 50 mL&#47;min <a class="elsevierStyleCrossRef" href="#t0040">&#40;Table 8&#41;</a>&#46;</p><elsevierMultimedia ident="t0040"></elsevierMultimedia><p id="p0885" class="elsevierStylePara elsevierViewall">Hepatitis C virus &#40;HCV&#41; infection is a risk factor of a variety of extrahepatic diseases&#44; such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis &#40;MPGN&#41;&#44; which is the most common glomerulonephritis&#46; In these cases&#44; treatment is indicated in order to eliminate the antigen-stimulating process&#44; although therapy must be individualized&#44; as ribavirin is contraindicated in individuals with creatinine clearance &#60; 50 mL&#47;min&#44; pegylated interferon is poorly tolerated in end stage renal disease and is contraindicated in renal allograft recipients&#46; In addition&#44; when the autoimmune is process is very active&#44; it must be controlled first with the adequate inmunosuppresive therapy&#44; and once the patient is stabilized&#44; antiviral therapy may be considered&#46;</p><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Recommendations</span><p id="p0890" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0110"><li class="elsevierStyleListItem" id="list0525"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0895" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">HCV screening must be carried out in all renal patients under hemodialysis treatment who are considered for kidney transplantation <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0530"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0900" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A liver biopsy must be considered in all patients on hemodialysis who present with any spontaneous or unexplainable liver damage <span class="elsevierStyleBold">&#40;Class IIa&#44; Level C&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0535"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p0905" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The dose and type of treatment need to be based on the stage of renal function measured by the glomerular filtration rate of the patient&#44; and should always begin with the minimum doses <span class="elsevierStyleBold">&#40;Class IIb&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0540"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p0910" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In cases of glomerulonephritis associated to HCV infection&#44; antiviral therapy should be addressed in order to eliminate the antigen stimulated process&#46; <span class="elsevierStyleBold">&#40;Class IIa&#44; Level C&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Treatment of Acute Hepatitis</span><p id="p0915" class="elsevierStylePara elsevierViewall">It has been found that treatment of acute episodes of HCV infection not only gives more satisfactory responses&#44; but also prevents chronic infection&#46; In a metaanalysis of 16 studies&#44; it was observed a difference in the risk of evolving to a chronic state after treatment of 49&#37; &#40;95&#37; confidence interval&#44; 33&#37;&#8211;65&#37;&#41;&#46;</p><p id="p0920" class="elsevierStylePara elsevierViewall">Several studies have also demonstrated a preference for initiating treatment 12 weeks after virus identification&#44; allowing some time for the spontaneous disappearance of the virus in that period &#40;52&#37;&#8211;67&#37;&#41;&#46; Spontaneous resolution tends to occur in patients with genotype 3&#44; low viral load&#44; female sex&#44; and white ethnicity&#59; black ethnicity&#44; HIV coinfection&#44; and advanced age favor viral persistence and chronic disease&#46;</p><p id="p0925" class="elsevierStylePara elsevierViewall">It has been observed that patients with jaundice and fluctuating viremia seem to benefit from late treatment&#44; whereas patients with HCV genotype 1 and high viral load respond better to early treatment&#46;</p><p id="p0930" class="elsevierStylePara elsevierViewall">There is no consensus about optimal treatment doses&#46; Several studies have found satisfactory responses with monotherapy of interferon at doses of 5 million U&#47;day for a minimum of 8 weeks&#44; or pegylated interferon alpha 2b at doses above 1&#46;2&#8211;1&#46;33 mg&#47;kg&#47;week for 12 weeks&#46; Although high doses of interferon seem to have more benefit&#44; there are no studies that show any noteworthy benefit with the combined use of ribavirin or with schemes longer than 12 weeks&#46;</p><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Recommendations</span><p id="p0935" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0115"><li class="elsevierStyleListItem" id="list0545"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0940" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Every patient with acute HCV infection without negative characteristics for spontaneous clearance &#40;genotype 1&#44; black race&#44; HIV coinfection&#44; or advanced age&#41; must be under careful surveillance for 12 weeks before initiation of treatment because of the possibility of a spontaneous resolution <span class="elsevierStyleBold">&#40;Class IIa&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0550"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p0945" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment ought to be initiated with monotherapy of pegylated interferon 1&#46;2 mg&#47;kg&#47;week for at least 12 weeks or interferon 5 million U&#47;day for a minimum of 8 weeks <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Treatment of Hcv&#47;Hbv Coinfection</span><p id="p0950" class="elsevierStylePara elsevierViewall">Hepatitis C and B viruses are the most frequent causes of chronic liver disease worldwide and coinfection may occur because they share the same routes of transmission&#46; Coinfection with these two viruses implies a more serious disease because it has a greater risk of progression to HCC than HCV monoinfection&#46; It is calculated that between 9&#37; and 30&#37; of patients with HCV are coinfected with HBV&#46; Several studies have proven that HCV infection may suppress HBV replication&#44; thereby diminishing HBV surface antigen &#40;HBsAg&#41; and core antigen &#40;HBcAg&#41; expression&#44; an effect that is mainly observed in patients with genotype 1 HCV in which HBV diagnosis may be delayed for up to 6 weeks&#46;</p><p id="p0955" class="elsevierStylePara elsevierViewall">Treatment of patients coinfected with HCV and HBV must be considered because of the probability that they will develop cirrhosis and decompensated liver disease&#46;</p><p id="p0960" class="elsevierStylePara elsevierViewall">Liver transplantation should be considered in decompensated patients&#46; Likewise&#44; antiviral treatment must be selected on the basis of serological indices &#40;HBeAg&#44; anti-HBe&#41; and levels of HBV DNA and HCV RNA&#44; in order to know what virus replication is predominating&#46; Several studies have demonstrated that combined therapy with interferon alpha 2b at doses of 6 million units three times per week for 12 weeks&#44; followed by 3 million units three times per week for another 12 weeks plus ribavirin 1&#44;200 mg daily for 24 weeks is effective in these patients&#46; Recent data show that peginterferon alpha 2a &#40;180 mg&#41; weekly for 48 weeks and ribavirin &#40;1&#44;000&#8211;1&#44;200 mg&#41; daily is equally effective in patients with HCV monoinfection and in those with chronic HBV&#47;HCV coinfection&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> Some authors recommend combined therapy with lamivudine at doses of 100 mg daily&#46; Both therapeutic regimens show an adequate clearance response&#46;</p><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Recommendations</span><p id="p0965" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0120"><li class="elsevierStyleListItem" id="list0555"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0970" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Combined treatment with pegylated interferon plus ribavirin and triple antiviral treatments both give similar rates of SVR and are the currently recommended treatment <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Treatment for Hcv and Hiv Coinfection</span><p id="p0975" class="elsevierStylePara elsevierViewall">Approximately 25&#37; of HIV-infected patients are coinfected with HCV&#46; Thus&#44; detection tests for HCV must be performed in every HIV-infected patient and vice versa before beginning treatment&#44; being aware that almost 6&#37; of HIV patients do not develop anti-HCV antibodies&#44; so HCV-RNA quantification is necessary&#46;</p><p id="p0980" class="elsevierStylePara elsevierViewall">Several studies report that only 4&#37; or 5&#37; of HIV-infected patients show spontaneous resolution of their HCV infection and response to treatment is not as fast or as sustained as in patients infected only with HCV&#46; Furthermore&#44; coinfection promotes the development of cirrhosis as much as twice as frequently as monoinfection with HCV&#59; this is why it must be detected in time to initiate treatment that favors antiretroviral therapy&#46;</p><p id="p0985" class="elsevierStylePara elsevierViewall">Currently&#44; the recommendation on treatment is pegylated interferon plus ribavirin for 48 weeks at the same doses used in HCV monoinfection&#46; However&#44; hemolytic anemia caused by ribavirin must be considered because it is more common in patients with this coinfection&#44; especially when antiretroviral treatment includes zidovudine or didanosine&#46; Interaction between didanosine and ribavirin in-creases risk of lactic acidosis and should be avoided&#46; Interferon&#44; on the other hand&#44; reduces the number of CD4&#43; cells while maintaining their percentage&#44; so does not favor the development of opportunistic infections&#46; Furthermore&#44; it has been found that patients treated with pegylated interferon show reductions of approximately 0&#46;7 log in HIV-RNA levels&#46;</p><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Recommendations</span><p id="p0990" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0125"><li class="elsevierStyleListItem" id="list0560"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p0995" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Every HIV-infected patient ought to be screened for HCV and vice versa <span class="elsevierStyleBold">&#40;Class IIa&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0565"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1000" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Diagnosis of HCV in HIV-infected patients must be confirmed through HCV-RNA quantification because of the false negatives of anti-HCV antibodies that may occur in this coinfection <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0570"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p1005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">At present&#44; treatment with pegylated interferon plus ribavirin for 48 weeks at the same doses used in HCV monoinfected patients is recommended with strict vigilance for adverse effects <span class="elsevierStyleBold">&#40;Class IIb&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0575"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p1010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Interaction between ribavirin and zidavudine and especially didanosine should be avoided&#46; Patients receiving these antiretroviral drugs should be switched to other therapies before starting treatment for hepatitis C&#46;</span></p></li></ul></p></span></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Management of Side Effects of Hepatitis C Treatment</span><p id="p1015" class="elsevierStylePara elsevierViewall">Although many HCV infections are asymptomatic&#44; there can be side effects to drug administration&#46; Depending on the doses&#44; frequency&#44; or pathway of administration&#44; between 10&#37; and 15&#37; of patients suffer these side effects&#46;</p><p id="p1020" class="elsevierStylePara elsevierViewall">Among the most common symptoms are flu-like symptoms&#44; fatigue&#44; headache&#44; thyroid dysfunction&#44; anorexia&#44; digestive disorders&#44; depression&#44; and anemia&#46; Most of these symptoms are tolerable and are easily controlled with an adjustment in dose or frequency of administration&#46; Unfortunately&#44; 10&#37;&#8211;15&#37; of patients drop out of treatment because of these symptoms&#44; which evidently affects the response to antiviral treatment&#46;</p><p id="p1025" class="elsevierStylePara elsevierViewall">Side effects related to the combined use of pegylated interferon plus ribavirin correspond to those produced by the separate components&#46; The most common side effects produced by interferon are flulike symptoms&#44; fatigue&#44; anorexia&#44; weight loss&#44; alopecia&#44; insomnia&#44; depression&#44; anemia&#44; neutropenia&#44; thrombocytopenia&#44; and Hashimoto thyroiditis&#46; No reports have shown an important difference between side effects of the different interferons&#46; Among the side effects produced by ribavirin&#44; the most frequent is hemolytic anemia and the second most common is pruritus&#46;</p><p id="p1030" class="elsevierStylePara elsevierViewall">In cases of neutropenia &#40;which occurs in about 30&#37; of patients&#41; &#60; 750 cells&#47;mL&#44; the interferon dose must be reduced by half&#59; however&#44; in cases of neutropenia &#60; 500 cells&#47;mL&#44; treatment must be suspended and reinitiated with a half-normal dose once the neutrophil count is restored&#46; In cases of thrombocytopenia &#40;12&#37;&#41;&#44; the treatment must&#44; again&#44; be reduced by half if values are &#60; 50&#44;000 cells&#47;mm<span class="elsevierStyleSup">3</span> and suspended at values of &#60; 20&#44;000 cells&#47;mm<span class="elsevierStyleSup">3</span>&#46;</p><p id="p1035" class="elsevierStylePara elsevierViewall">Although anemia is common &#40;50&#37;&#41; and completely reversible with the suspension of treatment&#44; when hemoglobin &#40;Hb&#41; levels are &#60; 10 g&#47;dL&#44; ribavirin doses must be reduced by half&#46; If 4 weeks after dose reduction Hb is &#60; 8&#46;5 g&#47;dL&#44; treatment must be suspended&#46; In some cases &#40;Hb &#60; 12 g&#47;dL and no contraindications&#41;&#44; erythropoietin can be administered at doses of 40&#44;000 to 60&#44;000 IU&#47;week&#46;</p><p id="p1040" class="elsevierStylePara elsevierViewall">Depression is also common among HCV patients and is common as a side effect &#40;6&#37;&#41;&#44; especially among IVDU&#44; alcoholics&#44; and those with multiple comorbidities&#46; A nonhepatotoxic treatment of citalopram 5 mg&#47;day&#44; paroxetin 5&#8211;30 mg&#47;day&#44; or sertralin 25&#8211;100 mg&#47;day is recommended&#46;</p><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Recommendations</span><p id="p1045" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0130"><li class="elsevierStyleListItem" id="list0580"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p1050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment of side effects should be symptomatic and opportune to avoid treatment dropouts <span class="elsevierStyleBold">&#40;Class IIa&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0585"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In cases of anemia of Hb &#60; 10 g&#47;dL&#44; ribavirin doses must be reduced by half and reevaluated in 4 weeks&#59; in cases where it continues or worsens&#44; treatment should be suspended and erythropoietin must be administered at doses of 40&#44;000&#8211;60&#44;000 IU&#47;week <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0590"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p1060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In cases of neutropenia with &#60; 750 cells&#47;mL&#44; interferon doses should be reduced by half and suspended if neutrophils &#60; 500 cells&#47;mL&#46; Treatment should be reinitiated at a half-dose once the neutrophil count is restored <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span><ul class="elsevierStyleList" id="li0135"><li class="elsevierStyleListItem" id="list0595"><span class="elsevierStyleLabel">&#8226;</span><p id="p1065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A granulocyte colony stimulating factor is recommended for the treatment of neutropenia <span class="elsevierStyleBold">&#40;Class IIa&#44; Level C&#41;&#46;</span></span></p></li></ul></p></li><li class="elsevierStyleListItem" id="list0600"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p1070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In cases of thrombocytopenia &#60; 50&#44;000 cells&#47;mm<span class="elsevierStyleSup">3</span>&#44; the interferon dose must be reduced by half or suspended if the count is &#60; 20&#44;000 cells&#47;mm<span class="elsevierStyleSup">3</span><span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0605"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">5&#46;</span></span><p id="p1075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Every patient with depression must be treated with citalopram 5 mg&#47;day&#44; paroxetin 5&#8211;30 mg&#47;day&#44; or sertralin 25&#8211;100 mg&#47;day to avoid poor compliance with base treatment <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">New Approaches to Hcv Treatment</span><p id="p1080" class="elsevierStylePara elsevierViewall">HCV therapy is under study in order to improve the response among patients&#46; New options are needed because of the following two situations&#46;<ul class="elsevierStyleList" id="li0140"><li class="elsevierStyleListItem" id="list0610"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p1085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The response to treatment has been shown to depend on viral genotype&#44; viral load&#44; ethnicity&#44; and recently the presence of the IL-28B gene&#44; and it is noted that available therapies have lower efficacy in Latin American patients&#46;</span></p></li><li class="elsevierStyleListItem" id="list0615"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">If disease is mild&#44; patients can wait for better therapies&#46;</span></p></li><li class="elsevierStyleListItem" id="list0620"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p1095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">There are several side effects of treatment with pegylated interferon and ribavirin&#46;</span></p></li></ul></p><p id="p1100" class="elsevierStylePara elsevierViewall">The most advanced drugs in development are the protease and polymerase inhibitors&#46; The protease inhibitors interfere with the translation of HCV and the polymerase inhibitors act by interfering with viral replication <a class="elsevierStyleCrossRef" href="#t0045">&#40;Table 9&#41;</a>&#46;</p><elsevierMultimedia ident="t0045"></elsevierMultimedia><p id="p1105" class="elsevierStylePara elsevierViewall">Recent studies have shown that protease inhibitors such as telaprevir or boceprevir&#44; combined with pegylated interferon and ribavirin&#44; achieve efficacy rates of more than 70&#37; in na&#239;ve patients with genotype 1 HCV&#46; It has been demonstrated that the efficacy rate for white Latin Americans is around 34&#37;&#46;</p><p id="p1110" class="elsevierStylePara elsevierViewall">The polymerase inhibitors are either analogs or nonnucleoside inhibitors&#46; The nucleoside analogs are active site inhibitors that require conversion to the active triphosphate&#46; The nucleosides affect a highly conserved region of the genome and have a high genetic barrier to resistance&#46; These inhibitors are active against genotypes 2 and 3&#46; None of them is yet available because most are in phase 2 trials&#46;</p><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Recommendations</span><p id="p1115" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0145"><li class="elsevierStyleListItem" id="list0625"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p1120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Those infected with HCV genotype 1 or 4 who are na&#239;ve-to-treatment and without advanced liver disease could wait for direct-acting antiviral &#40;DAA&#41; treatment&#44; especially because results from telaprevir-and boceprevir-based triple therapies have shown improved response rates <span class="elsevierStyleBold">&#40;Class IIa&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0630"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Those infected with HCV genotype 1 or 4 with significant liver disease should be treated with pegylated interferon and ribavirin&#46; In the case of no response&#44; a triple therapy could be considered <span class="elsevierStyleBold">&#40;Class IIa&#44; Level C&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Insulin Resistance&#44; Metabolic Syndrome&#44; and their Implications in HCV Infection</span><p id="p1130" class="elsevierStylePara elsevierViewall">Insulin resistance &#40;IR&#41;&#44; defined as the pathophysiological condition in which higher than normal concentrations of insulin are required to maintain normal levels of glycemia&#44; is closely related to the development of such pathological states as obesity&#44; diabetes mellitus type 2 &#40;DM2&#41;&#44; and nonalcoholic fatty liver disease &#40;NAFLD&#41;&#44; which is the most frequent hepatopathy in Western countries&#46; Several studies have found that it is present in 30&#37; to 70&#37; of HCV-infected patients and that it increases the risk of developing DM2 in HCV-positive patients&#46;</p><p id="p1135" class="elsevierStylePara elsevierViewall">Hepatic steatosis is present more often in patients with HCV genotype 3&#44; which has been implicated as pathogenic in its development&#46; However&#44; this has given way to the conclusion that in non-genotype 3 HCV&#44; the cause of the steatosis is IR&#46;</p><p id="p1140" class="elsevierStylePara elsevierViewall">In HCV-infected patients&#44; it has been found that the worsening of IR and associated pathologies is caused by effects on the insulin receptor substrates &#40;IRS&#41; and the generation of proinflammatory cytokines&#46; NAFLD is promoted because of the increase in lipogenesis caused by IR and the metabolism of fatty acids&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> This&#44; in addition to the proinflammatory state&#44; favors its evolution to steatohepatitis&#44; cirrhosis&#44; and HCC&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> Clinical repercussions of IR have been demonstrated in several studies in which it was concluded that IR diminishes the response to antiviral treatment independent of the viral genotype&#44; evolution of liver damage and fibrosis&#44; or development of DM2&#46;</p><p id="p1145" class="elsevierStylePara elsevierViewall">Some studies have suggested that reduction of body weight before initiating HCV treatment gives a better response&#46; They have also suggested the use of insulin-sensitizing agents such as pioglitazone and metformin&#44; and although the studies have found some differences that favor late virological response &#40;LVR&#41; or slightly favor SVR&#44; they have failed to find a significant improvement with the use of these agents&#44; for which more studies are needed&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">74</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a></p><span id="sec0215" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Recommendations</span><p id="p1150" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0150"><li class="elsevierStyleListItem" id="list0635"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p1155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">All HCV-infected patients must have a metabolic assessment that includes HOMA-IR measurement <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0640"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Weight loss ought to be recommended in all HCV-infected patients who are overweight or obese&#44; preferably before initiation of HCV treatment <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0645"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p1165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Use of insulin-sensitizing agents must be individualized depending on comorbidities <span class="elsevierStyleBold">&#40;Class IIb&#44; Level B&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Hepatitis C and Hepatocellular Carcinoma &#40;Hcc&#41;</span><p id="p1170" class="elsevierStylePara elsevierViewall">In several regions of the world &#40;especially in Asia and Africa&#41;&#44; a strong association is found between HBV infection&#44; HCV&#44; and alcoholic cirrhosis&#44; and the development of HCC&#46; In Oceania and both North and South America&#44; the last two entities tend to be the principal risk factors in the development of this hepatic neoplasm&#46; Small multicenter studies in some regions of America and Latin America confirm the presence of HCV in patients with HCC&#46;</p><p id="p1175" class="elsevierStylePara elsevierViewall">Several risk factors have been related to the genesis of HCC&#46; The main risk factor in HCV-infected patients is the presence of cirrhosis&#46; Although the incidence is much lower in noncirrhotic patients&#44; there are also other risk factors related to host&#44; virus&#44; and some external factors&#46; For the host&#44; risk factors include advanced age &#40;&#62; 50 years&#41;&#44; male sex&#44; thrombocytopenia&#44; esophageal varices&#44; and comorbidities&#46; For viral variables&#44; a controversial meta-analysis showed that patients with HCV genotype 1b have twice the normal risk of developing HCC&#46; Other studies&#44; also meta-analyses&#44; report that active or occult&#44; but not past&#44; HBV infection correlates with the development of this pathology&#44; whereas HIV coinfection promotes the advance to cirrhosis&#46; Finally&#44; for external factors&#44; heavy alcohol intake doubles the possibility of evolution to HCC compared with those who do not drink&#46; Treatment with interferon for any other cause besides hepatitis C acts as protection against the development of HCC&#46;</p><span id="sec0225" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">Recommendations</span><p id="p1180" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0155"><li class="elsevierStyleListItem" id="list0650"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p1185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Every patient with HCV must be monitored because of the risk of developing HCC&#44; especially those with cirrhosis&#44; HBV or HIV coinfection&#44; or chronic alcoholism <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0655"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Monitoring must be performed by ultrasonography every 6 months <span class="elsevierStyleBold">&#40;Class IIa&#44; Level A&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">Hepatitis C Treatment&#58; Cost-Efficacy&#44; Cost-Benefit</span><p id="p1195" class="elsevierStylePara elsevierViewall">The impact of HCV infection is high and will tend to increase in the future&#46; There are registers in some Latin American countries that suggest that the infection is the second most frequent cause of cirrhosis and that its prevalence will increase to more than 70&#37;&#46; It also favors the evolution of liver disease from the infiltrative stage to inflammatory&#44; necroinflammatory&#44; and neoplasmic stages with their corresponding functional loss and diminishment in quality-adjusted life years&#46;</p><p id="p1200" class="elsevierStylePara elsevierViewall">Objectives of treatment are to eliminate the virus and stop the progression of liver damage&#46; To do so&#44; SVR is valued because it is associated with improvement of liver function&#44; liver histology&#44; and quality of life&#46; Pegylated interferon combined with ribavirin is currently considered the therapy with the best response&#46; Some models indicate that if this treatment were given to 10&#37; of infected patients&#44; a reduction of 6&#37; in morbidity and 4&#37; in mortality would occur&#44; and if it were given to 50&#37; of patients the reductions would be of 26&#37; and 20&#37;&#44; respectively&#46;</p><span id="sec0235" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Recommendations</span><p id="p1205" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0160"><li class="elsevierStyleListItem" id="list0660"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p1210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Preventive measures must be emphasized and actions directed to minimize risk factors should be taken in order to reduce the incidence of infection <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0665"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1215" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Every HCV-infected patient must have individualized treatment analyzing his&#47;her predictive and risk factors in order to reduce morbidity and mortality caused by the infection <span class="elsevierStyleBold">&#40;Class I&#44; Level B&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0670"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p1220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Elective treatment for patients with no associated risk factors must be with combined pegylated interferon plus ribavirin <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li></ul></p></span></span><span id="sec0240" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Medical and Legal Implications of Hepatitis C</span><p id="p1225" class="elsevierStylePara elsevierViewall">HCV infection is a worldwide public health issue&#46; There are many routes of transmission that are used to define certain risk groups&#58; patients with a history of blood transfusion before 1992&#44; hemophiliacs&#44; IVDU&#44; patients in treatment with hemodialysis&#44; patients who have had acupuncture&#44; patients with tattoos&#44; patients with multiple sexual partners&#44; newborns to infected mothers&#44; and healthcare workers&#46; Prevalence in this last group&#44; for which healthcare worker-patient&#44; patient-healthcare worker&#44; and patient-patient transmission is a reality&#44; varies from 1&#37; to 10&#37;&#46; The first and second routes occur especially among surgeons who are in direct contact with patient tissues during any interven-tion&#59; the third route is more obvious given the outbreaks in some hemodialysis centers&#46;</p><p id="p1230" class="elsevierStylePara elsevierViewall">Currently&#44; prevention is considered the main route to avoid viral transmission&#46; Screening of every blood donor and of every patient with documented IV drug use&#44; history of transfusion before 1992&#44; in hemodialysis&#44; or with evidence of hepatopathy is recommended&#46; Use of body protection for healthcare personnel is another recommendation&#46; Not every country recommends routine screening within this group&#44; but usually only after exposure&#46;</p><p id="p1235" class="elsevierStylePara elsevierViewall">There are no regulations to follow post exposure&#46; Each institution follows its own protocol&#46; Generally it is recommended to wash the exposed site &#40;antiseptics and disinfectants have not provided better preventive indexes&#44; but neither are they contraindicated&#41; and to screen both the medical personnel and the patient for HBV&#44; HCV&#44; and HIV&#46; Although there is no indication for suspending normal activities&#44; some countries&#44; such as Germany&#44; do promote it until viral loads of less than 1 x 10<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> IU&#47;mL are reported&#46;</p><span id="sec0245" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">Recommendations</span><p id="p1240" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0165"><li class="elsevierStyleListItem" id="list0675"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">1&#46;</span></span><p id="p1245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Routine screening of every patient with the following risk factors&#58; hemotransfused before 1992&#44; IVDU&#44; and&#47;or people with multiple sexual partners or with any identified liver disease <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0680"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">2&#46;</span></span><p id="p1250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Routine screening of healthcare workers <span class="elsevierStyleBold">&#40;Class IIb&#44; Level C&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0685"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">3&#46;</span></span><p id="p1255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Use of body protection for medical personnel at every point during which contact is established with exposed patient tissues <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0690"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">4&#46;</span></span><p id="p1260" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Reinforcement of healthcare personnel education regarding protection and techniques of injection&#44; taking of blood samples&#44; minor surgeries&#44; and other procedures in which they have contact with exposed patients&#8217; blood <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span></span></p></li><li class="elsevierStyleListItem" id="list0695"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">5&#46;</span></span><p id="p1265" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In case of exposure of the healthcare worker to patient blood products&#44; the exposure site must be washed with soap and water&#44; and samples for HBV&#44; HCV&#44; and HIV analysis taken for both the healthcare worker and the patient <span class="elsevierStyleBold">&#40;Class I&#44; Level A&#41;&#46;</span> The following steps should be taken&#58;</span><ul class="elsevierStyleList" id="li0170"><li class="elsevierStyleListItem" id="list0700"><span class="elsevierStyleLabel">&#8226;</span><p id="p1270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Measure ALT activity&#46;</span></p></li><li class="elsevierStyleListItem" id="list0705"><span class="elsevierStyleLabel">&#8226;</span><p id="p1275" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Follow up with new blood samples of the affected healthcare worker in 4&#8211;6 months&#46;</span></p></li><li class="elsevierStyleListItem" id="list0710"><span class="elsevierStyleLabel">&#8226;</span><p id="p1280" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Confirm diagnosis of HCV with HCV-RNA quantification or anti-HCV by RIBA&#46;</span></p></li></ul></p></li></ul></p></span></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:27 [
        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Preamble"
        ]
        1 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Introduction"
        ]
        2 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Epidemiology"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        3 => array:3 [
          "identificador" => "sec0025"
          "titulo" => "Transmission Routes"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Diagnosis"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        5 => array:3 [
          "identificador" => "sec0045"
          "titulo" => "Utility of Liver Biopsy in Chronic Infection"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Use of Noninvasive Methods to Evaluate The Stage of Liver Fibrosis"
        ]
        7 => array:3 [
          "identificador" => "sec0060"
          "titulo" => "Indications and Contraindications for the Treatment of Hcv Infection"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        8 => array:3 [
          "identificador" => "sec0070"
          "titulo" => "Predictive Factors for the Response to Treatment"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        9 => array:3 [
          "identificador" => "sec0080"
          "titulo" => "Hepatitis C Treatment in Na&#239;ve Patients"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        10 => array:3 [
          "identificador" => "sec0090"
          "titulo" => "Approach and Management of Patients With Normal Levels of Transaminases"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        11 => array:3 [
          "identificador" => "sec0100"
          "titulo" => "Treatment in Cirrhotic Patients"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        12 => array:3 [
          "identificador" => "sec0110"
          "titulo" => "Treatment in Posttransplantation Patients"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0115"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        13 => array:3 [
          "identificador" => "sec0120"
          "titulo" => "Treatment in Nonresponders and Relapsers"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0125"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        14 => array:3 [
          "identificador" => "sec0130"
          "titulo" => "Management of Hcv Infection in Pregnant Women"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0135"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        15 => array:3 [
          "identificador" => "sec0140"
          "titulo" => "Management of Hcv Infection in Children"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0145"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        16 => array:3 [
          "identificador" => "sec0150"
          "titulo" => "Treatment of HCV-Infected Patients with Kidney Disease"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0155"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        17 => array:3 [
          "identificador" => "sec0160"
          "titulo" => "Treatment of Acute Hepatitis"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0165"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        18 => array:3 [
          "identificador" => "sec0170"
          "titulo" => "Treatment of Hcv&#47;Hbv Coinfection"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0175"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        19 => array:3 [
          "identificador" => "sec0180"
          "titulo" => "Treatment for Hcv and Hiv Coinfection"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0185"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        20 => array:3 [
          "identificador" => "sec0190"
          "titulo" => "Management of Side Effects of Hepatitis C Treatment"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0195"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        21 => array:3 [
          "identificador" => "sec0200"
          "titulo" => "New Approaches to Hcv Treatment"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0205"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        22 => array:3 [
          "identificador" => "sec0210"
          "titulo" => "Insulin Resistance&#44; Metabolic Syndrome&#44; and their Implications in HCV Infection"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0215"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        23 => array:3 [
          "identificador" => "sec0220"
          "titulo" => "Hepatitis C and Hepatocellular Carcinoma &#40;Hcc&#41;"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0225"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        24 => array:3 [
          "identificador" => "sec0230"
          "titulo" => "Hepatitis C Treatment&#58; Cost-Efficacy&#44; Cost-Benefit"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0235"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        25 => array:3 [
          "identificador" => "sec0240"
          "titulo" => "Medical and Legal Implications of Hepatitis C"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0245"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        26 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "multimedia" => array:9 [
      0 => array:6 [
        "identificador" => "t0005"
        "etiqueta" => "<span class="elsevierStyleBold">Table 1&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="npara0005" class="elsevierStyleSimplePara elsevierViewall">Adapted from&#58; Ghany MG&#44; Strader DB&#44; Thomas DL&#44; Seeff LB&#46; Diagnosis&#44; management and treatment of hepatitis C&#58; an update&#46; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">Hepatology</span></span> 2009&#59; 49&#40;4&#41;&#58; 1335&#8211;74&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Classification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Class I</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Conditions for which there is evidence or general consensus that the particular diagnostic procedure or treatment is beneficial&#44; useful&#44; and effective&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Class II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Conditions for which there is conflicting evidence and&#47;or divergence in opinions about the utility and efficacy of a diagnostic evaluation&#44; procedure&#44; or treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Class IIa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">The weight of evidence&#47;opinion is in favor of utility and efficacy&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Class IIb</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">The utility and&#47;or efficacy are less well established by evidence or opinion&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Class III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Conditions in which there is evidence or general consensus that a diagnostic evaluation&#44; procedure&#44; or treatment is not useful or effective and in some cases may cause damage&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066301.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Evidence level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Level A</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Data derived from multiple randomized studies or meta-analysis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Level B</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Data derived from only one randomized study or nonrandomized studies&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Level C</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Experts&#8217; opinions&#44; case studies&#44; or treatment standards&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066299.png"
              ]
            ]
          ]
        ]
      ]
      1 => array:7 [
        "identificador" => "t0010"
        "etiqueta" => "<span class="elsevierStyleBold">Table 2&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">General population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Blood donors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">IVDU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Hemodialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Coinfection with HBV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Mexico</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">6&#46;7&#37;<a class="elsevierStyleCrossRef" href="#t2fn1"><span class="elsevierStyleSup">2</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Dominican Republic</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">2&#46;4&#37;<a class="elsevierStyleCrossRef" href="#t2fn1"><span class="elsevierStyleSup">4</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">49&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Puerto Rico</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">2&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Costa Rica</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;3&#8211;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;2&#8211;0&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#37;<a class="elsevierStyleCrossRef" href="#t2fn1"><span class="elsevierStyleSup">1</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Venezuela</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">71&#37;<a class="elsevierStyleCrossRef" href="#t2fn1"><span class="elsevierStyleSup">3</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Brazil</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;32&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Peru</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">51&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Chile</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Argentina</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">2&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">0&#46;79&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">62&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">19&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">30&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066302.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "t2fn1"
              "etiqueta" => "<span class="elsevierStyleSup">1</span>"
              "nota" => "<p class="elsevierStyleNotepara" id="np0010">Pati&#241;o J&#44; Hevia F&#44; Saenz R&#44; Nu&#241;ez P&#44; Rodr&#237;guez R&#44; Horwitz D&#44; Flores J&#46; Trabajo 69 XIII Jornadas Latinoamericanas de Hepatologia&#46; <span class="elsevierStyleItalic">Rev Gastroenterol Mex</span> 1994&#59; 59&#40;suppl&#46; 2&#41;&#46; <span class="elsevierStyleSup">2</span>M&#233;ndez-S&#225;nchez N&#44; Motola-Kuba D&#44; Ch&#225;vez-Tapia NC&#44; et al&#46; Prevalence of hepatitis C virus infection among hemodialysis patients at a tertiary-care hospital in Mexico City&#44; Mexico&#46; <span class="elsevierStyleItalic">J Clin Microbiol</span> 2004&#59; 42&#58; 4321&#8211;2&#46; <span class="elsevierStyleSup">3</span>Pujol FH&#44; Ponce JG&#44; Lema MG&#44; et al&#46; High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence&#46; <span class="elsevierStyleItalic">J Clin Microbiol</span> 1996&#59; 34&#58; 1633&#8211;6&#46; <span class="elsevierStyleSup">4</span>Hogar Crea Dominicano&#46; Propuesta para proyecto&#46; Proyecto de capacitaci&#243;n y sensibilizaci&#243;n en relaci&#243;n a las ITS el VIH y el SIDA con ex-usuarios de drogas &#40;UD&#41; comunidades residenciales de Hogar Crea Dominicano&#46;&#44; Inc&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Prevalence of HCV in different risk groups&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "t0015"
        "etiqueta" => "<span class="elsevierStyleBold">Table 3&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">IASL<a class="elsevierStyleCrossRef" href="#t3fn1"><span class="elsevierStyleSup">1</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Metavir<a class="elsevierStyleCrossRef" href="#t3fn1"><span class="elsevierStyleSup">2</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Non fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Non fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Mild fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Periportal fibrotic expansion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Moderate fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Periportal septa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Severe fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Portocentral septa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066303.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "t3fn1"
              "etiqueta" => "<span class="elsevierStyleSup">1</span>"
              "nota" => "<p class="elsevierStyleNotepara" id="np0015">Desmet VJ&#44; Gerber M&#44; Hoofnagle JH&#44; Manns M&#44; Scheuer PJ&#46; Classification of chronic hepatitis&#58; diagnosis&#44; grading and staging&#46; <span class="elsevierStyleItalic">Hepatology</span> 1994&#59; 19&#58; 1513&#8211;20&#46; <span class="elsevierStyleSup">2</span>Bedossa P&#44; Poynard T&#46; An algorithm for the grading of activity in chronic hepatitis C&#46; The METAVIR cooperative study group&#46; <span class="elsevierStyleItalic">Hepatology</span> 1996&#59; 24&#58; 289&#8211;93&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Fibrosis evaluation scales&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "t0020"
        "etiqueta" => "<span class="elsevierStyleBold">Table 4&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><ul class="elsevierStyleList" id="li0005"><li class="elsevierStyleListItem" id="list0005"><span class="elsevierStyleLabel">&#8226;</span><p id="p0005" class="elsevierStylePara elsevierViewall">Age 18 to 70 years&#46;</p></li><li class="elsevierStyleListItem" id="list0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0010" class="elsevierStylePara elsevierViewall">HCV antibody positive in serum&#46;</p></li><li class="elsevierStyleListItem" id="list0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0015" class="elsevierStylePara elsevierViewall">Positive for HCV RNA&#46;</p></li><li class="elsevierStyleListItem" id="list0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0020" class="elsevierStylePara elsevierViewall">Hepatic biopsy&#58; chronic hepatitis with significant fibrosis&#46;</p></li><li class="elsevierStyleListItem" id="list0025"><span class="elsevierStyleLabel">&#8226;</span><p id="p0025" class="elsevierStylePara elsevierViewall">Compensated liver disease&#46;<ul class="elsevierStyleList" id="li0010"><li class="elsevierStyleListItem" id="list0030"><span class="elsevierStyleLabel">&#176;</span><p id="p0030" class="elsevierStylePara elsevierViewall">Absence of gastroesophagic varicose veins&#46;</p></li><li class="elsevierStyleListItem" id="list0035"><span class="elsevierStyleLabel">&#176;</span><p id="p0035" class="elsevierStylePara elsevierViewall">Total bilirubin &#60; 1&#46;5 g&#47;dL&#46;</p></li><li class="elsevierStyleListItem" id="list0040"><span class="elsevierStyleLabel">&#176;</span><p id="p0040" class="elsevierStylePara elsevierViewall">International normalized ratio &#40;INR&#41; &#60; 1&#46;5&#46;</p></li><li class="elsevierStyleListItem" id="list0045"><span class="elsevierStyleLabel">&#176;</span><p id="p0045" class="elsevierStylePara elsevierViewall">Albumin &#62; 3&#46;4 g&#47;100mL&#46;</p></li><li class="elsevierStyleListItem" id="list0050"><span class="elsevierStyleLabel">&#176;</span><p id="p0050" class="elsevierStylePara elsevierViewall">Platelet count of 75&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#46;</p></li><li class="elsevierStyleListItem" id="list0055"><span class="elsevierStyleLabel">&#176;</span><p id="p0055" class="elsevierStylePara elsevierViewall">No evidence of hepatic decompensation &#40;hepatic encephalopathy or ascites&#41;&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="list0060"><span class="elsevierStyleLabel">&#8226;</span><p id="p0060" class="elsevierStylePara elsevierViewall">Hemoglobin &#8805; 13 g&#47;dL for men and 12 g&#47;dL for women&#46;</p></li><li class="elsevierStyleListItem" id="list0065"><span class="elsevierStyleLabel">&#8226;</span><p id="p0065" class="elsevierStylePara elsevierViewall">Neutrophil count &#8805; 1500&#47;mm<span class="elsevierStyleSup">3</span>&#46;</p></li><li class="elsevierStyleListItem" id="list0070"><span class="elsevierStyleLabel">&#8226;</span><p id="p0070" class="elsevierStylePara elsevierViewall">Creatinine &#60; 1&#46;5 mg&#47;dL&#46;</p></li><li class="elsevierStyleListItem" id="list0075"><span class="elsevierStyleLabel">&#8226;</span><p id="p0075" class="elsevierStylePara elsevierViewall">Willingness to be treated&#46;</p></li><li class="elsevierStyleListItem" id="list0080"><span class="elsevierStyleLabel">&#8226;</span><p id="p0080" class="elsevierStylePara elsevierViewall">No contraindications&#46;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066294.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Characteristics of patients for whom therapy is recommended&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "t0025"
        "etiqueta" => "<span class="elsevierStyleBold">Table 5&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><ul class="elsevierStyleList" id="li0015"><li class="elsevierStyleListItem" id="list0085"><span class="elsevierStyleLabel">&#8226;</span><p id="p0085" class="elsevierStylePara elsevierViewall">Major uncontrolled depressive disorder and other mental disturbances&#46;</p></li><li class="elsevierStyleListItem" id="list0090"><span class="elsevierStyleLabel">&#8226;</span><p id="p0090" class="elsevierStylePara elsevierViewall">Posttransplantation patients&#46;</p></li><li class="elsevierStyleListItem" id="list0095"><span class="elsevierStyleLabel">&#8226;</span><p id="p0095" class="elsevierStylePara elsevierViewall">Autoimmune diseases that might be exacerbated by treatment with pegylated interferon&#46;</p></li><li class="elsevierStyleListItem" id="list0100"><span class="elsevierStyleLabel">&#8226;</span><p id="p0100" class="elsevierStylePara elsevierViewall">Untreated thyroid disease&#46;</p></li><li class="elsevierStyleListItem" id="list0105"><span class="elsevierStyleLabel">&#8226;</span><p id="p0105" class="elsevierStylePara elsevierViewall">Pregnancy&#46;</p></li><li class="elsevierStyleListItem" id="list0110"><span class="elsevierStyleLabel">&#8226;</span><p id="p0110" class="elsevierStylePara elsevierViewall">Severe comorbidity such as arterial hypertension&#44; heart failure&#44; uncontrolled diabetes mellitus&#44; chronic obstructive pulmonary disease&#44; or epilepsy&#46;</p></li><li class="elsevierStyleListItem" id="list0115"><span class="elsevierStyleLabel">&#8226;</span><p id="p0115" class="elsevierStylePara elsevierViewall">Age under 2 years&#46;</p></li><li class="elsevierStyleListItem" id="list0120"><span class="elsevierStyleLabel">&#8226;</span><p id="p0120" class="elsevierStylePara elsevierViewall">Known hypersensitivity to treatment&#46;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066296.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Contraindications for HCV treatment&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "t0030"
        "etiqueta" => "<span class="elsevierStyleBold">Table 6&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="npara0020" class="elsevierStyleSimplePara elsevierViewall">Modified from&#58; Jen J&#44; Laughlin M&#44; Chung C&#44; et al&#46; Ribavirin dosing in chronic hepatitis C&#58; application of population pharmacokinetic-pharmacodynamic models&#46; <span class="elsevierStyleItalic">Clin Pharmacol Ther</span> 2002&#59; 72&#40;4&#41;&#58; 349&#8211;61&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Weight &#40;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Ribavirin dose &#40;mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><span class="elsevierStyleBold">&#60; 65</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">800&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><span class="elsevierStyleBold">65&#8211;85</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#44;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><span class="elsevierStyleBold">85&#8211;105</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#44;200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><span class="elsevierStyleBold">&#62; 105</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#44;400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066298.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Ribavirin dose by weight&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "t0035"
        "etiqueta" => "<span class="elsevierStyleBold">Table 7&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="npara0025" class="elsevierStyleSimplePara elsevierViewall">Airoldi J&#44; Berghella V&#46; Hepatitis C and pregnancy&#46; <span class="elsevierStyleItalic">Obst Gynecol Surv</span> 2006&#59; 61&#58; 10&#46; Plunkett B&#44; Grobman W&#46; Routine hepatitis C virus screening in pregnancy&#58; A cost-effectiveness analysis&#46; <span class="elsevierStyleItalic">Am J Obst Gynecol</span> 2005&#59; 192&#58;1153&#8211;61&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><ul class="elsevierStyleList" id="li0020"><li class="elsevierStyleListItem" id="list0125"><span class="elsevierStyleLabel">&#8226;</span><p id="p0125" class="elsevierStylePara elsevierViewall">Women with history of blood derivatives transfusion especially before 1992&#46;</p></li><li class="elsevierStyleListItem" id="list0130"><span class="elsevierStyleLabel">&#8226;</span><p id="p0130" class="elsevierStylePara elsevierViewall">Women with history of IVDU&#46;</p></li><li class="elsevierStyleListItem" id="list0135"><span class="elsevierStyleLabel">&#8226;</span><p id="p0135" class="elsevierStylePara elsevierViewall">Patients and healthcare workers involved in dialysis programs&#46;</p></li><li class="elsevierStyleListItem" id="list0140"><span class="elsevierStyleLabel">&#8226;</span><p id="p0140" class="elsevierStylePara elsevierViewall">Women with HIV or HBV infection&#46;</p></li><li class="elsevierStyleListItem" id="list0145"><span class="elsevierStyleLabel">&#8226;</span><p id="p0145" class="elsevierStylePara elsevierViewall">Sexual partners of patients infected with HIV&#44; HBV&#44; or HCV&#46;</p></li><li class="elsevierStyleListItem" id="list0150"><span class="elsevierStyleLabel">&#8226;</span><p id="p0150" class="elsevierStylePara elsevierViewall">Women with a history of tattooing and&#47;or piercing&#46;</p></li><li class="elsevierStyleListItem" id="list0155"><span class="elsevierStyleLabel">&#8226;</span><p id="p0155" class="elsevierStylePara elsevierViewall">Transplantation recipients especially before 1992&#46;</p></li><li class="elsevierStyleListItem" id="list0160"><span class="elsevierStyleLabel">&#8226;</span><p id="p0160" class="elsevierStylePara elsevierViewall">Women with high levels of transaminases&#46;</p></li><li class="elsevierStyleListItem" id="list0165"><span class="elsevierStyleLabel">&#8226;</span><p id="p0165" class="elsevierStylePara elsevierViewall">Participants in in vitro fertilization programs with anonymous donors&#46;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066295.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Indications for screening in pregnant women&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "t0040"
        "etiqueta" => "<span class="elsevierStyleBold">Table 8&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="npara0030" class="elsevierStyleSimplePara elsevierViewall">IFN&#58; Interferon&#46; GFR&#58; Glomerular filtration rate&#46; Modified from&#58; Ghany MG&#44; Strader DB&#44; Thomas DL&#44; Seeff LB&#46; Diagnosis&#44; Management and treatment of Hepatitis C&#58; An update&#46; <span class="elsevierStyleItalic">Hepatology</span> 2009&#59; 49&#40;4&#41;&#58;1335&#8211;74&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Kidney damage with conserved or slightly elevated GFR &#40;&#62; 90 mL&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Usual combined therapy depending on viral genotype&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Kidney damage with mildly affected GFR &#40;60&#8211;90 mL&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Usual combined therapy depending on viral genotype&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Moderately affected GFR &#40;30&#8211;59 mL&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2b 1 &#956;g&#47;kg&#47;week&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2a 135 &#956;g&#47;kg&#47;week &#43; Ribavirin 200&#8211;800 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Severely affected GFR &#40;15&#8211;29 mL&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2b 1 &#956;g&#47;kg&#47;week&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2a 135 &#956;g&#47;kg&#47;week &#43; Ribavirin 200&#8211;800 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Chronic renal failure &#40;GFR &#60; 15 mL&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2b 1 &#956;g&#47;kg&#47;week&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2a 135 &#956;g&#47;kg&#47;week &#43; Ribavirin 200&#8211;800 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">5D</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Dialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">IFN 2a or 2b 3 mU&#47;3 times per week&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2b 1 &#956;g&#47;kg&#47;week&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2a&#44; 135 &#956;g&#47;kg&#47;week &#43; Ribavirin 200&#8211;800 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Cryoglobulinemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Control of the acute event with immunosuppressants and then&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">INF2a or 2b 3 mU&#47;3 times per week&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2b 1 &#956;g&#47;kg&#47;week&#59; or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PegIFN&#945;-2a&#44; 135 &#956;g&#47;kg&#47;week &#43; Ribavirin 200&#8211;800 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066297.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Treatment according to stage of renal dysfunction&#46;</p>"
        ]
      ]
      8 => array:7 [
        "identificador" => "t0045"
        "etiqueta" => "<span class="elsevierStyleBold">Table 9&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Enzyme inhibi tors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Genome sequence-based&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Protease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">RNA interference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Modifications of IFN and ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Albinterferon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-PEGIFN lambda &#40;IL-29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Taribavirin &#40;viramidine&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">Polymerase</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Antisense&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Immunological&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Therapeutic vaccines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Toll-like receptor agonists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Hepatitis C immunoglobulin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Monoclonal antibodies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle"><span class="elsevierStyleBold">NS5A</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">Targeting cellular factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Cyclophilin antagonists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Nitazoxanide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-mIR-122 inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">-Entry inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2066300.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Emer ging Therapies for HCV&#46; Specifically targeted antiviral treatment &#40;STAT-C&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bs0005"
          "bibliografiaReferencia" => array:76 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Discovery of the Hepatitis C virus&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Houghton M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1478-3231.2008.01925.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Liver Int"
                        "fecha" => "2009"
                        "volumen" => "29"
                        "numero" => "S1"
                        "paginaInicial" => "82"
                        "paginaFinal" => "88"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19207970"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National consensus of Hepatitis C&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Coordinaci&#243;n General de los Institutos Nacionales de Salud&#44; Asociaci&#243;n Mexicana de Hepatolog&#237;a&#46;"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Hepatol"
                        "fecha" => "2002"
                        "volumen" => "1"
                        "numero" => "3"
                        "paginaInicial" => "148"
                        "paginaFinal" => "154"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15280815"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Estimating the future health burden of chronic hepatitis C and human immunodeficiency virus infections in the United States&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Deuffic-Burban S"
                            1 => "Poynard T"
                            2 => "Sulkowski MS"
                            3 => "Wong JB"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2893.2006.00785.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Viral Hepat"
                        "fecha" => "2007"
                        "volumen" => "14"
                        "paginaInicial" => "107"
                        "paginaFinal" => "115"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17244250"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Trends in liver disease prevalence in Mexico from 2005 to 2050 through mortality data&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#233;ndez-S&#225;nchez N"
                            1 => "Villa AR"
                            2 => "Chavez-Tapia N"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Hepatol"
                        "fecha" => "2005"
                        "volumen" => "4"
                        "numero" => "1"
                        "paginaInicial" => "52"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15798662"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Projecting future complications of chronic hepatitis C in the United States&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Davis GL"
                            1 => "Albright JE"
                            2 => "Cook SF"
                            3 => "Rosenberg DM"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jlts.2003.50073"
                      "Revista" => array:6 [
                        "tituloSerie" => "Liver Transpl"
                        "fecha" => "2003"
                        "volumen" => "9"
                        "paginaInicial" => "331"
                        "paginaFinal" => "338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12682882"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis&#44; management and treatment of Hepatitis C&#58; An update&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Ghany MG"
                            1 => "Strader DB"
                            2 => "Thomas DL"
                            3 => "Seeff LB"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.22759"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2009"
                        "volumen" => "49"
                        "numero" => "4"
                        "paginaInicial" => "1335"
                        "paginaFinal" => "1374"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19330875"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of hepatitis B and C viruses&#58; A global overview&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Te HS"
                            1 => "Jensen DM"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Liv Dis"
                        "fecha" => "2010"
                        "volumen" => "14"
                        "paginaInicial" => "1"
                        "paginaFinal" => "21"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low prevalence of anti-hepatitis C virus antibodies in Mexico&#58; A systematic review&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Chiquete E"
                            1 => "Panduro A"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000096306"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intervirology"
                        "fecha" => "2007"
                        "volumen" => "50"
                        "paginaInicial" => "1"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17164551"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Seroprevalencia de la hepatitis C en adultos de M&#233;xico&#58; &#191;Un problema de salud p&#250;blica emergente&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Valdespino JL"
                            1 => "Conde-Gonz&#225;lez CJ"
                            2 => "Olaiz-Fern&#225;ndez G"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Salud P&#250;blica Mex"
                        "fecha" => "2007"
                        "volumen" => "49"
                        "numero" => "Suppl 3"
                        "paginaInicial" => "S395"
                        "paginaFinal" => "S403"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Pereira MLB et al&#46; Congresso Brasileiro de Hepatologia&#46; 2009&#46;"
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Secretar&#237;a de Estado de Salud P&#250;blica y Asistencia Social &#40;SESPAS&#41;&#46; Enfermedad Hepatitis C&#46; Santo Domingo R&#46;D&#46;"
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Seroepidemiology of viral hepatitis&#44; HIV and herpes simplex type 2 in the household population aged 21-64 years in Puerto Rico&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "P&#233;rez M"
                            1 => "Marrero E"
                            2 => "Mel&#233;ndez M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2334-10-76"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Infect Dis"
                        "fecha" => "2010"
                        "volumen" => "10"
                        "paginaInicial" => "76"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20331884"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Santana B&#44; Guerrero F&#46; Prevalencia de infecciones de transmisi&#243;n sexual en mujeres residentes en Bateyes del ingenio Barahona&#46; Organizaci&#243;n Panamericana de la Salud OPS&#47;OMS&#46; Programa conjunto de las Naciones Unidas sobre el VIH&#47;SIDA &#40;ONUSIDA&#41;&#46; 2001&#46;"
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Presentaciones en even-tos nacionales&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Hevia F"
                            1 => "San Roman M"
                            2 => "Aguero O"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Revista M&#233;dica de Costa Rica"
                        "fecha" => "1992"
                        "paginaInicial" => "518"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Hevia F&#44; San Roman M&#44; Aguero O&#46; Hepatitis virales 1993&#46;"
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Hevia F&#44; San Roman M&#44; Aguero O&#46; Medicina Legal de Costa Rica 1994&#59; 11"
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of hepatitis C virus in Peru and Latin America&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#225;valos Moscol M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Gastroenterol Peru"
                        "fecha" => "2009"
                        "volumen" => "29"
                        "paginaInicial" => "347"
                        "paginaFinal" => "354"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20066020"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence and prevalence of hepatitis C virus infection in Chile&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Gonz&#225;lez R"
                            1 => "Soza A"
                            2 => "Hern&#225;ndez V"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Hepatol&#46;"
                        "fecha" => "2005"
                        "volumen" => "4"
                        "paginaInicial" => "127"
                        "paginaFinal" => "130"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16010246"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#8220;Hepatitis C en Chile&#58; Magnitud del problema&#8221;&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Soza A"
                            1 => "L&#243;pez-Lastra M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "/S0034-98872006000600016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Med Chil"
                        "fecha" => "2006"
                        "volumen" => "134"
                        "paginaInicial" => "777"
                        "paginaFinal" => "788"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17130955"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Schroder T y la Asociaci&#243;n Argentina para el Estudio de las Enfermedades del Hfgado&#46; Conclusiones del Consenso Argentino Hepatitis C 2007&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Fassio E"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Acta Gastroenter Latinoamer"
                        "fecha" => "2008"
                        "volumen" => "38"
                        "paginaInicial" => "56"
                        "paginaFinal" => "74"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The changing epidemiology of hepatitis C virus infection in Europe&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Esteban JI"
                            1 => "Sauleda S"
                            2 => "Quer J"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2007.07.033"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2008"
                        "volumen" => "48"
                        "paginaInicial" => "148"
                        "paginaFinal" => "162"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18022726"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for hepatitis C virus infection in United States blood donors&#46; NHLBI Retrovirus Epidemiology Donor Study &#40;REDS&#41;&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Murphy EL"
                            1 => "Bryzman SM"
                            2 => "Glynn SA"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.510310329"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2000"
                        "volumen" => "31"
                        "paginaInicial" => "756"
                        "paginaFinal" => "762"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10706569"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transmission of hepatitis C virus from mothers to infants&#46; The Vertical Transmission of Hepatitis C Virus Collaborative Study Group&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Ohto H"
                            1 => "Terazawa S"
                            2 => "Sasaki N"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199403173301103"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1994"
                        "volumen" => "330"
                        "paginaInicial" => "744"
                        "paginaFinal" => "750"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8107740"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mother-to-infant transmission of hepatitis C virus&#46; Lombardy Study Group on Vertical HCV Transmission&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Zanetti AR"
                            1 => "Tanzi E"
                            2 => "Paccagnini S"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0140-6736(95)90277-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1995"
                        "volumen" => "345"
                        "paginaInicial" => "289"
                        "paginaFinal" => "291"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7530793"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "McIntyre PG"
                            1 => "Tosh K"
                            2 => "McGuire W"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2006"
                        "paginaInicial" => "CD005546"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of hepatitis C virus infection among hemodialysis patients at a tertiary-care hospital in Mexico City&#44; Mexico&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#233;ndez-S&#225;nchez N"
                            1 => "Motola-Kuba D"
                            2 => "Chavez-Tapia NC"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.42.9.4321-4322.2004"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2004"
                        "volumen" => "42"
                        "paginaInicial" => "4321"
                        "paginaFinal" => "4322"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15365034"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Pujol FH"
                            1 => "Ponce JG"
                            2 => "Lema MG"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "1996"
                        "volumen" => "34"
                        "paginaInicial" => "1633"
                        "paginaFinal" => "1636"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8784559"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "MMWR Recomm Rep"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Updated U&#46;S&#46; Public Health Service guidelines for the management of occupational exposures to HBV&#44; HCV&#44; and HIV and recommendations for postexposure prophylaxis&#46;"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "fecha" => "2001"
                        "volumen" => "50"
                        "paginaInicial" => "1"
                        "paginaFinal" => "52"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Natural history of chronic hepatitis C&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Seeff LB"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jhep.2002.36806"
                      "Revista" => array:8 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2002"
                        "volumen" => "36"
                        "numero" => "Suppl"
                        "paginaInicial" => "S35"
                        "paginaFinal" => "S46"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12407575"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S014067361161516X"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "How can we predict treatment response&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Selzner N MI"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:5 [
                        "editores" => "Al Ave"
                        "titulo" => "Advances in the Therapy of Liver Disease&#46;"
                        "paginaInicial" => "271"
                        "paginaFinal" => "277"
                        "serieFecha" => "1997"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C&#58; A randomized trial&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Manns MP"
                            1 => "McHutchison JG"
                            2 => "Gordon SC"
                            3 => "Rustgi VK"
                            4 => "Shiffman M"
                            5 => "Reindollar R"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0140-6736(01)06102-5"
                      "Revista" => array:8 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2001"
                        "volumen" => "358"
                        "numero" => "9286"
                        "paginaInicial" => "958"
                        "paginaFinal" => "965"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11583749"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1474442203004022"
                          "estado" => "S300"
                          "issn" => "14744422"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Fried MW"
                            1 => "Shiffman ML"
                            2 => "Reddy KR"
                            3 => "Smith C"
                            4 => "Marinos G"
                            5 => "Goncales FLJ"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa020047"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2002"
                        "volumen" => "347"
                        "numero" => "13"
                        "paginaInicial" => "975"
                        "paginaFinal" => "982"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12324553"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C virus&#58; A critical appraisal of approaches to therapy&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Nelson DR"
                            1 => "Davis GL"
                            2 => "Jacobson I"
                            3 => "Everson GT"
                            4 => "Fried MW"
                            5 => "Harrison SA"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2008.11.016"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol"
                        "fecha" => "2009"
                        "volumen" => "7"
                        "numero" => "4"
                        "paginaInicial" => "397"
                        "paginaFinal" => "414"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19114127"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adherence to combination therapy enhances sustained response in genotype 1 infected patients with chronic hepatitis C&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "McHutchinson JG"
                            1 => "Manns M"
                            2 => "Patel K"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2002"
                        "volumen" => "123"
                        "paginaInicial" => "1061"
                        "paginaFinal" => "1069"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12360468"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic variation in IL-28B predicts hepatitis C treatment-induced viral clearance&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Ge D"
                            1 => "Fellay J"
                            2 => "Thompson AJ"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature08309"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2009"
                        "volumen" => "461"
                        "paginaInicial" => "399"
                        "paginaFinal" => "401"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19684573"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C&#58; Systematic review of randomized trials&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Awad T"
                            1 => "Thorlund K"
                            2 => "Hauser G"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.23504"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2010"
                        "volumen" => "51"
                        "numero" => "4"
                        "paginaInicial" => "1176"
                        "paginaFinal" => "1184"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20187106"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peginterferon alpha 2a and ribavirin combination therapy in chronic hepatitis C&#58; A randomized study of treatment duration and ribavirin dose&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Hadziyannis SJ"
                            1 => "Sette H Jr"
                            2 => "Morgan TR"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-140-5-200403020-00010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2004"
                        "volumen" => "140"
                        "paginaInicial" => "346"
                        "paginaFinal" => "355"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14996676"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of liver disease in a population of asymptomatic individuals with hepatitis C virus infection&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Alberti A"
                            1 => "Noventa F"
                            2 => "Benvegn&#249; L"
                            3 => "Boccato S"
                            4 => "Gatta A"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-137-12-200212170-00009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2002"
                        "volumen" => "137"
                        "paginaInicial" => "961"
                        "paginaFinal" => "964"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12484711"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Volunteer blood donors with antibody to hepatitis C virus&#58; Clinical&#44; biochemical&#44; virologic&#44; and histologic features&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Shakil AO"
                            1 => "Conry-Cantilena C"
                            2 => "Alter HJ"
                            3 => "Hayashi P"
                            4 => "Kleiner DE"
                            5 => "Tedeschi V"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-123-5-199509010-00002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "1995"
                        "volumen" => "123"
                        "paginaInicial" => "330"
                        "paginaFinal" => "337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7542854"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C virus carriers with persistently normal aminotransferase levels&#58; healthy people or true patients&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Puoti C"
                            1 => "Castellacci R"
                            2 => "Montagnese F"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Dig Liver Dis"
                        "fecha" => "2000"
                        "volumen" => "32"
                        "paginaInicial" => "634"
                        "paginaFinal" => "643"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11142566"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical&#44; histological&#44; and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Puoti C"
                            1 => "Magrini A"
                            2 => "Stati T"
                            3 => "Rigato P"
                            4 => "Montagnese F"
                            5 => "Rossi P"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jhep.1997.v26.pm0009397976"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1997"
                        "volumen" => "26"
                        "paginaInicial" => "1393"
                        "paginaFinal" => "1398"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9397976"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Viral and metabolic factors influencing alanine aminotransferase activity in patients with chronic hepatitis C&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Prati D"
                            1 => "Shiffman ML"
                            2 => "Diago M"
                            3 => "Gane E"
                            4 => "Rajender Reddy K"
                            5 => "Pockros P"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2006.01.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2006"
                        "volumen" => "44"
                        "paginaInicial" => "679"
                        "paginaFinal" => "685"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16487620"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors associated with serum alanine transaminase activity in healthy subjects&#58; consequences for the definition of normal values&#44; for selection of blood donors&#44; and for patients with chronic hepatitis C&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Piton A"
                            1 => "Poynard T"
                            2 => "Imbert-Bismut F"
                            3 => "Khalil L"
                            4 => "Delattre J"
                            5 => "Pelissier E"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.510270505"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1998"
                        "volumen" => "27"
                        "paginaInicial" => "1213"
                        "paginaFinal" => "1219"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9581673"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HCV carriers with persistently normal aminotransferase levels&#58; Normal does not always mean healthy&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Puoti C"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2003"
                        "volumen" => "38"
                        "paginaInicial" => "529"
                        "paginaFinal" => "532"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12663249"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Braks RE"
                            1 => "Ganne-Carrie N"
                            2 => "Fontaine H"
                            3 => "Paries J"
                            4 => "Grando-Lemaire V"
                            5 => "Beaugrand M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3748/wjg.v13.i42.5648"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Gastroenterol"
                        "fecha" => "2007"
                        "volumen" => "13"
                        "paginaInicial" => "5648"
                        "paginaFinal" => "5653"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17948941"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin&#46; Review&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Berenguer M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2008.05.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2008"
                        "volumen" => "49"
                        "paginaInicial" => "274"
                        "paginaFinal" => "287"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18571272"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Peveling-Oberhag J"
                            1 => "Zeuzem S"
                            2 => "Hofmann WP"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00430-009-0131-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Microbiol Immunol"
                        "fecha" => "2010"
                        "volumen" => "199"
                        "paginaInicial" => "1"
                        "paginaFinal" => "10"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19902246"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of hepatitis C in liver transplant recipients&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Gordon FD"
                            1 => "Kwo P"
                            2 => "Vargas HE"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Liver Transplant"
                        "fecha" => "2009"
                        "volumen" => "15"
                        "paginaInicial" => "126"
                        "paginaFinal" => "135"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C and liver transplantation&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Brown RS"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature04083"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2005"
                        "volumen" => "436"
                        "paginaInicial" => "973"
                        "paginaFinal" => "978"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16107838"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The natural history of hepatitis C cirrhosis after liver transplantation&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Firpi RJ"
                            1 => "Clark V"
                            2 => "Soldevila-Pico C"
                            3 => "Morelli G"
                            4 => "Cabrera R"
                            5 => "Levy C"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Liver Transplant"
                        "fecha" => "2009"
                        "volumen" => "15"
                        "paginaInicial" => "1063"
                        "paginaFinal" => "1071"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Everson GT"
                            1 => "Trotter J"
                            2 => "Forman L"
                            3 => "Kugelmas M"
                            4 => "Halprin A"
                            5 => "Fey B"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.20793"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2005"
                        "volumen" => "42"
                        "paginaInicial" => "255"
                        "paginaFinal" => "262"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16025497"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Should we treat patients with chronic hepatitis C on the waiting list&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Everson GT"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2005.01.010"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2005"
                        "volumen" => "42"
                        "paginaInicial" => "447"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15763324"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antiviral therapy in HCV-infected cirrhotics awaiting liver transplantation&#58; a costly strategy for mixed virological results&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Roche B"
                            1 => "Samuel D"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2009.01.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2009"
                        "volumen" => "50"
                        "paginaInicial" => "652"
                        "paginaFinal" => "654"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19231019"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Peveling-Oberhag J"
                            1 => "Zeuzem S"
                            2 => "Hofmann WP"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00430-009-0131-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Microbiol Immunol"
                        "fecha" => "2010"
                        "volumen" => "199"
                        "paginaInicial" => "1"
                        "paginaFinal" => "10"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19902246"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The natural history of hepatitis C cirrhosis after liver transplantation&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Firpi RJ"
                            1 => "Clark V"
                            2 => "Soldevila-Pico C"
                            3 => "Morelli G"
                            4 => "Cabrera R"
                            5 => "Levy C"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Liver Transplant"
                        "fecha" => "2009"
                        "volumen" => "15"
                        "paginaInicial" => "1063"
                        "paginaFinal" => "1071"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Preemptive therapy for hepatitis C virus after living-donor liver transplantation&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Sugawara Y"
                            1 => "Makuuchi M"
                            2 => "Matsui Y"
                            3 => "Kishi Y"
                            4 => "Akamatsu N"
                            5 => "Kaneko J"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "2004"
                        "volumen" => "78"
                        "paginaInicial" => "1308"
                        "paginaFinal" => "1311"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15548968"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Applicability&#44; tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Shergill AK"
                            1 => "Khalili M"
                            2 => "Straley S"
                            3 => "Bollinger K"
                            4 => "Roberts JP"
                            5 => "Ascher NA"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1600-6143.2004.00648.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Transplant"
                        "fecha" => "2005"
                        "volumen" => "5"
                        "paginaInicial" => "118"
                        "paginaFinal" => "124"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15636619"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peginterferon alfa-2a for hepatitis C after liver transplantation&#58; two randomized&#44; controlled trials&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Chalasani N"
                            1 => "Manzarbeitia C"
                            2 => "Ferenci P"
                            3 => "Vogel W"
                            4 => "Fontana RJ"
                            5 => "Voigt M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.20560"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2005"
                        "volumen" => "41"
                        "paginaInicial" => "289"
                        "paginaFinal" => "298"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15660392"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Peginterferon alpha 2a &#40;40kDa&#41; and rivabirin&#58; comparable rates of sustained virological response in sub-sets of older and younger HCV genotype 1 patients&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "REddy KR"
                            1 => "Messinger D"
                            2 => "Popescu M"
                            3 => "Hadziyannis SJ"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2893.2009.01122.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Viral Hepat"
                        "fecha" => "2009"
                        "volumen" => "16"
                        "paginaInicial" => "724"
                        "paginaFinal" => "731"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19486469"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of disease severity on outcome of antiviral therapy for chonic hepatitis C&#58; lessons from the HALT-C trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Everson GT"
                            1 => "Hoefs JC"
                            2 => "Seeff LB"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.21440"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2006"
                        "volumen" => "44"
                        "paginaInicial" => "1675"
                        "paginaFinal" => "1684"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17133499"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomized trial of pegylated interferon alpha 2b plus ribavirin in the retreatment of chronic hepatitis C&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Jacobson IM"
                            1 => "Gonzalez SA"
                            2 => "Ahmed F"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1572-0241.2005.00282.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol"
                        "fecha" => "2005"
                        "volumen" => "100"
                        "paginaInicial" => "2453"
                        "paginaFinal" => "2462"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16279900"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C y embarazo&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Garcia W"
                            1 => "Lopez J"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Rev Gastroenterol Peru"
                        "fecha" => "2006"
                        "paginaInicial" => "275"
                        "paginaFinal" => "282"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pregnancy and esophageal varices&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Britton RC"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg"
                        "fecha" => "1982"
                        "volumen" => "143"
                        "numero" => "4"
                        "paginaInicial" => "412"
                        "paginaFinal" => "415"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pregnancy in liver cirrhosis and&#47; or portal hypertension&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Cheng Y"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Am J Obst Gynecol"
                        "fecha" => "1977"
                        "volumen" => "128"
                        "paginaInicial" => "812"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Possible role of high titer maternal viremia in perinatal transmission of hepatitis C virus&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Lin HH"
                            1 => "Kao JH"
                            2 => "Hsu HY"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/infdis/169.3.638"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1994"
                        "volumen" => "169"
                        "paginaInicial" => "638"
                        "paginaFinal" => "641"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8158040"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mother-to-infant transmission of hepatitis C&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Bernard O"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Gastroenterol Belg"
                        "fecha" => "1998"
                        "volumen" => "61"
                        "paginaInicial" => "192"
                        "paginaFinal" => "194"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9658606"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Follow up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women&#58; The role of breast-feeding in transmission&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Ruiz-Extremera A"
                            1 => "Salmeron J"
                            2 => "Torres C"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "2000"
                        "volumen" => "19"
                        "paginaInicial" => "511"
                        "paginaFinal" => "516"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10877164"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C virus&#46; HCV genotypes in 373 Italian children with HCV infection&#58; changing distribution and correlation with clinical features and outcome&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Bortolotti F"
                            1 => "Resti M"
                            2 => "Marcellini M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2004.053744"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2005"
                        "volumen" => "54"
                        "paginaInicial" => "852"
                        "paginaFinal" => "857"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15888796"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Italian Observatory for HCV Infection and Hepatitis C in Children&#46; Epidemio-logical profile of 806 Italian Children with hepatitis C virus infection over a 15-year period&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Bortolotti F"
                            1 => "Jorio R"
                            2 => "Resti M"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2006.12.014"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2007"
                        "volumen" => "46"
                        "paginaInicial" => "783"
                        "paginaFinal" => "790"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17321633"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic viral hepatitis in children&#58; any role for the pathologist&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Guido M"
                            1 => "Bortolotti F"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2007.139410"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2008"
                        "volumen" => "57"
                        "paginaInicial" => "873"
                        "paginaFinal" => "877"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18559378"
                             …1
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Perinatal hepatitis C virus infection&#58; Diagnosis and management&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/adc.2005.081877"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dis Child"
                        "fecha" => "2006"
                        "volumen" => "91"
                        "paginaInicial" => "781"
                        "paginaFinal" => "785"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha 2a and ribavirin&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1746.2007.04904.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Gastroenterol Hepatol"
                        "fecha" => "2007"
                        "volumen" => "22"
                        "paginaInicial" => "832"
                        "paginaFinal" => "836"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic syndrome and nonalcoholic fatty liver disease&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Hepatol"
                        "fecha" => "2009"
                        "volumen" => "8"
                        "numero" => "1"
                        "paginaInicial" => "S18"
                        "paginaFinal" => "S24"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Los efectos de los acidos grasos no esterificados sobre la matriz extracelular de las c&#233;lulas vasculares podr&#237;an contribuir a una respuesta aterog&#233;nica&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Progreso M&#233;dico"
                        "fecha" => "2000"
                        "volumen" => "9"
                        "numero" => "1"
                        "paginaInicial" => "45"
                        "paginaFinal" => "53"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology and natural history of non-alcoholic fatty liver disease &#40;NAFLD&#41;&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Hepatol"
                        "fecha" => "2009"
                        "volumen" => "8"
                        "numero" => "1"
                        "paginaInicial" => "S4"
                        "paginaFinal" => "S8"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insulin resistance and response to antiviral therapy in chronic hepatitis C&#58; Mechanisms and management&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000282104"
                      "Revista" => array:7 [
                        "tituloSerie" => "Dig Dis"
                        "fecha" => "2010"
                        "volumen" => "28"
                        "numero" => "1"
                        "paginaInicial" => "285"
                        "paginaFinal" => "293"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317181/v1_201906221034/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "78188"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Special Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16652681/00000009000000S1/v1_201906221034/S1665268119317181/v1_201906221034/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317181?idApp=UINPBA00004N"
]

Article information

ISSN: 16652681
Original language: English

DOI:10.1016/S1665-2681(19)31718-1

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	2	0	2
2024 October	13	1	14
2024 September	8	2	10
2024 August	12	1	13
2024 July	16	1	17
2024 June	10	3	13
2024 May	7	4	11
2024 April	8	4	12
2024 March	7	4	11
2024 February	8	5	13
2024 January	7	5	12
2023 December	11	4	15
2023 November	9	8	17
2023 October	12	7	19
2023 September	7	3	10
2023 August	4	2	6
2023 July	8	2	10
2023 June	3	3	6
2023 May	9	2	11
2023 April	2	0	2
2023 March	2	0	2
2023 February	6	1	7
2023 January	9	2	11
2022 December	7	3	10
2022 November	14	3	17
2022 October	16	4	20
2022 September	9	3	12
2022 August	8	5	13
2022 July	8	6	14
2022 June	6	6	12
2022 May	15	6	21
2022 April	19	9	28
2022 March	15	6	21
2022 February	6	4	10
2022 January	5	3	8
2021 December	6	6	12
2021 November	4	6	10
2021 October	6	8	14
2021 September	3	6	9
2021 August	3	3	6
2021 July	9	6	15
2021 June	5	11	16
2021 May	5	4	9
2021 April	12	8	20
2021 March	6	5	11
2021 February	5	4	9
2021 January	2	9	11
2020 December	3	3	6
2020 November	1	7	8
2020 October	2	5	7
2020 September	4	3	7
2020 August	3	2	5
2020 July	2	1	3
2020 June	3	1	4
2020 May	1	4	5
2020 April	2	0	2
2020 March	3	2	5
2020 February	4	1	5
2020 January	1	3	4
2019 December	5	11	16
2019 November	0	3	3
2019 October	3	3	6
2019 September	2	0	2
2019 August	1	2	3
2019 July	2	2	4
2019 June	1	3	4

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter