Approach to and management of patients with chronic hepatitis C virus infection and normal transaminase levels
Read
765
Timeswas read the article
253
Total PDF
512
Total HTML
Share statistics
array:24 [ "pii" => "S1665268119319684" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31968-4" "estado" => "S300" "fechaPublicacion" => "2006-01-01" "aid" => "71627" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2006" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2006;5 Supl 1:S34-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 43 "formatos" => array:3 [ "EPUB" => 9 "HTML" => 16 "PDF" => 18 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119319696" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31969-6" "estado" => "S300" "fechaPublicacion" => "2006-01-01" "aid" => "71628" "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. 2006;5 Supl 1:S36-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 43 "formatos" => array:3 [ "EPUB" => 5 "HTML" => 15 "PDF" => 23 ] ] "en" => array:8 [ "idiomaDefecto" => true "titulo" => "Treatment of chronic hepatitis C infection in cirrhotic patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S36" "paginaFinal" => "S39" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lucy Dagher" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Lucy" "apellidos" => "Dagher" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119319696?idApp=UINPBA00004N" "url" => "/16652681/00000005000000S1/v1_201906280857/S1665268119319696/v1_201906280857/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119319672" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31967-2" "estado" => "S300" "fechaPublicacion" => "2006-01-01" "aid" => "71626" "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. 2006;5 Supl 1:S32-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 61 "formatos" => array:3 [ "EPUB" => 9 "HTML" => 27 "PDF" => 25 ] ] "en" => array:9 [ "idiomaDefecto" => true "titulo" => "Treatment of chronic hepatitis C in treatment-naïve patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S32" "paginaFinal" => "S33" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:6 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1204 "Ancho" => 1507 "Tamanyo" => 137869 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Isaac Quintero Samudio" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Isaac" "apellidos" => "Quintero Samudio" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119319672?idApp=UINPBA00004N" "url" => "/16652681/00000005000000S1/v1_201906280857/S1665268119319672/v1_201906280857/en/main.assets" ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Approach to and management of patients with chronic hepatitis C virus infection and normal transaminase levels" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S34" "paginaFinal" => "S35" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Nelia Hernández Maldonado" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Nelia" "apellidos" => "Hernández Maldonado" "email" => array:1 [ 0 => "nelia@adinet.com.uy" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Clínica de Gastroenterología del Hospital de Clínicas de Montevideo, Uruguay" "etiqueta" => "1" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Address for correspondence:" ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">Chronic infection with hepatitis C virus (HCV) is a dynamic disease from a biochemical perspective because transaminase levels fluctuate and may even fall within normal ranges at times. Although most patients with this disease have elevated alanine aminotransferase (ALT) levels, up to 46% of cases have persistently normal serum ALT levels despite the presence of HCV RNA.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Until recently, HCV patients with normal ALT levels were not considered for treatment because it was believed that this indicated that hepatic lesions were absent. The 1997 consensus conference<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> did not recommend HCV treatment for patients with normal transaminase levels. At the consensus conference of 2002,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> expert opinions regarding the site of the biopsy and the indications for treatment of patients with APN were divided. The following aspects of the management of APN patients are still the subject of debate.</p><p id="p0010" class="elsevierStylePara elsevierViewall">For how long should potential APN patients be monitored and at what intervals should analyses be done to determine whether they have APN?</p><p id="p0015" class="elsevierStylePara elsevierViewall">Most protocols define APN as at least three normal ALT values over a period of not less than 6 months.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>However, elevation of ALT levels may be delayed for 12 months in up to 21% of cases.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The shorter the follow-up period, the greater the possibility of misdiagnosis of patients.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Are persistently normal ALT levels indicative of the absence of hepatic lesions?</span><p id="p0020" class="elsevierStylePara elsevierViewall">Most histological studies in which the severity of lesions have been evaluated show that patients with APN have lower levels and activities of fibrosis than patients with elevated APN levels.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> However, significant fibrosis and even cirrhosis is present in 5%–19% of APN cases.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> These data show that liver damage cannot be presumed to be absent on the basis of a few ALT analyses.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">What is the natural evolution of hepatitis C in APN patients?</span><p id="p0025" class="elsevierStylePara elsevierViewall">Knowledge of the progression of fibrosis is fundamental for decisions about the evaluation and treatment of APN patients. Hui et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> showed that patients with APN and an FO/F1 level of fibrosis at the time of the initial biopsy tended to develop less severe levels of fibrosis than patients with the same grade of fibrosis but elevated ALT levels. The difference between these groups was not significant when the initial level of fibrosis was more severe (F2). Puoti et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> studied four couples of which one member had elevated ALT levels and the other had APN. Only patients with elevated ALT levels received treatment; the APN patients were denied treatment even if histological tests showed that they had hepatic lesions. A second biopsy 10 years after the first showed that the lesions had progressed from F0 to F3 and from F2 to F4 in the two untreated APN cases.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Are liver biopsies useful for initial evaluations? Is it important to take a biopsy sample prior to deciding on a treatment?</span><p id="p0030" class="elsevierStylePara elsevierViewall">Liver biopsy constitutes a reference method for evaluation of the level of damage and fibrosis (staging) of liver disease. ALT levels are not correlated with histological findings.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The usefulness of liver biopsies in patients with APN is controversial.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The consensus conferences of 1997 and 1999 of the NIH and EASL, respectively, do not recommend biopsies for this group of patients, nor do they recommend treatment.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In the consensus of the NIH of 2002,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> it was stated that larger studies on the usefulness of biopsies for this group of patients were required and that only those patients with favorable predictors of response to treatment, i.e., patients with HCV genotypes 2 or 3, should be treated. The most recent recommendations of the AASLD (The American Association for the Study of Liver Diseases) stated that liver biopsy is unnecessary, irrespective of ALT values.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> This recommendation and the absence of any clear ruling on the topic indicate that each case should be evaluated on an individual basis, taking many other factors into account.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Does the response to treatment differ between APN patients and those with elevated ALT levels?</span><p id="p0035" class="elsevierStylePara elsevierViewall">Although numbers of APN patients in studies of responses to treatment with interferon alfa plus ribavirin are low, they indicate that response rates of APN patients are similar to those of patients with elevated ALT levels.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In the first multicenter study to evaluate the efficacy and safety of peginterferon plus ribavirin, 491 patients with APN were studied 18 months before acceptance. The patients were randomized into three groups: 24 weeks of treatment, 48 weeks of treatment, and no treatment. The average SVR was 30% and 52% in patients treated for 24 and 48 weeks, respectively. In patients with HCV genotype 1, SVR after 48 weeks of treatment was 40%; in patients with HCV genotypes 2 or 3, SVR was 72% and 78% after 24 and 48 weeks of treatment, respectively.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Should the decision to treat patients be based on biochemical (ALT), histological (fibrosis) or genomic (PCR) criteria?</span><p id="p0040" class="elsevierStylePara elsevierViewall">The decision to treat patients should be based on all these criteria and also on aspects such as the age of patient, his/her motivation, the virus genotype, and the presence of comorbidities that constitute contraindications or major risks. Alberti et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> proposed an algorithm for treatment in which young individuals who are infected with genotypes 2 or 3 and are highly motivated and free of contraindications may receive treatment without the need for a biopsy. In patients older than 50 years with HCV genotypes 1 or 4 and co-morbidities, pre-treatment biopsies may constitute the decisive factors.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Recommendations of the consensus panel</span><p id="p0045" class="elsevierStylePara elsevierViewall">Should patients with normal transaminase levels be excluded from treatment?</p><p id="p0050" class="elsevierStylePara elsevierViewall">Patients with normal transaminase levels should be treated for as long as possible because several studies have shown that the risk-benefit ratio is justified. Although the panel did not reach consensus on whether it is necessary to take liver biopsies from this group of patients, most thought that this decision should made on an individual basis.</p><p id="p0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Evidence quality: 3</span></p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Are persistently normal ALT levels indicative of the absence of hepatic lesions?" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "What is the natural evolution of hepatitis C in APN patients?" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Are liver biopsies useful for initial evaluations? Is it important to take a biopsy sample prior to deciding on a treatment?" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Does the response to treatment differ between APN patients and those with elevated ALT levels?" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Should the decision to treat patients be based on biochemical (ALT), histological (fibrosis) or genomic (PCR) criteria?" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Recommendations of the consensus panel" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of liver disease in a population of asymptomatic persons with hepatitis C virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Alberti A" 1 => "Noventa F" 2 => "Benvegnu 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" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "National Institutes of Health Consensus Development Conference Panel statement: management of hepatitis C" ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.510260701" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "1997" "volumen" => "26" "numero" => "3 Suppl.1" "paginaInicial" => "2S" "paginaFinal" => "10S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9305656" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C: 2002 June 10-12" ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2002.37117" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2002" "volumen" => "36" "paginaInicial" => "S3" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12407572" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paris, 26-28 February 1999, Consensus Statement. European Association for the Study of the liver" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "EASL International Consensus Conference on Hepatitis C" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "1999" "volumen" => "30" "paginaInicial" => "956" "paginaFinal" => "961" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10365827" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Histological and virological features and follow up of HCV carriers with normal aminotransferase levels: the Italian Study of the Asymptomatic C Carriers (ISAAC)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Puoti C" 1 => "Castellacci R" 2 => "Montagneses F" 3 => "Zaltron S" 4 => "Stornaluolo G" 5 => "Bergami N" 6 => "Bellis L" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2002" "volumen" => "37" "paginaInicial" => "117" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12076870" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relationship between serum alanine aminotransferase levels and liver histology in chronic hepatitis C-infected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Taraneh D" 1 => "Ebrahimi D" 2 => "Mohammad B" 3 => "Ali-Asad H" 4 => "Babak H" 5 => "Ali-Reza S" 6 => "Madjid S." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Indian J Gastro" "fecha" => "2005" "volumen" => "24" "paginaInicial" => "49" "paginaFinal" => "51" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver biopsy in the evaluation of patients with chronic hepatitis C who have repeatedly normal or near-normal serum alanine aminotransferase levels" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Nut A.K." 1 => "Hassan H.A." 2 => "Lindsay J" 3 => "Lamps L.W." 4 => "Raufman JP." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0002-9343(00)00381-8" "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "2000" "volumen" => "109" "paginaInicial" => "62" "paginaFinal" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10936480" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic hepatitis C with normal or abnormal aminotransferase levels: is it the same entity?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:8 [ 0 => "Herve S" 1 => "Savoye G" 2 => "Riachi G" 3 => "Hellot M.F." 4 => "Gloria O" 5 => "Lerebours E" 6 => "Colin R" 7 => "Ducrotte P." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2001" "volumen" => "13" "paginaInicial" => "405" "paginaFinal" => "500" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11338071" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European Collaborative Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:8 [ 0 => "Pradat P" 1 => "Alberti A" 2 => "Poynard T" 3 => "Esteban J" 4 => "Eiland O" 5 => "Marcellin P" 6 => "Badallamenti S" 7 => "Trepo C." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2002.35530" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2002" "volumen" => "36" "paginaInicial" => "973" "paginaFinal" => "977" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12297846" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is liver biopsy necessary for hepatitis C virus carriers with persistently normal aminotransferase levels?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:8 [ 0 => "Pasquale G" 1 => "Sagnelli E" 2 => "Coppola N" 3 => "Scarano F" 4 => "Scolastico C" 5 => "Bellomo P" 6 => "Lettieri A" 7 => "Piccinino F." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.meg.0000059137.68845.e2" "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2003" "volumen" => "15" "paginaInicial" => "831" "paginaFinal" => "833" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12811317" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Hui C.K." 1 => "Belaye T" 2 => "Montegrande K" 3 => "Wright TL." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2003" "volumen" => "38" "paginaInicial" => "511" "paginaFinal" => "517" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12663245" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic hepatitis C and «normal» ALT levels: treat the disease not the test." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Puoti C" 1 => "Bellis L" 2 => "Martellino F" 3 => "Guarisco R" 4 => "Dell’Unto O" 5 => "Durola L" 6 => "Galossi A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2005.03.032" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2005" "volumen" => "43" "paginaInicial" => "534" "paginaFinal" => "535" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16023245" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A multicentre study of the usefulness of liver biopsy in hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:10 [ 0 => "Bain V.G." 1 => "Bonacini M" 2 => "Govindarajan S" 3 => "Ma M" 4 => "Sherman M" 5 => "Gibas A" 6 => "Cotler S.J." 7 => "Deschenes M" 8 => "Kaita K" 9 => "Jhangri G.S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2004.00520.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2004" "volumen" => "11" "paginaInicial" => "375" "paginaFinal" => "382" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15230861" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Experts opinions on the role of liver biopsy in HCV infection: a Delphi survey by the Italian Association of Hospital Gastroenterologists (A.I.G.O.)." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:10 [ 0 => "Almasio P.L." 1 => "Niero M" 2 => "Angioli D" 3 => "Ascione A" 4 => "Gullini S" 5 => "Minoli G" 6 => "Oprandi N" 7 => "Battista G" 8 => "Verme G" 9 => "Andriulli A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2005.02.041" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2005" "volumen" => "43" "paginaInicial" => "381" "paginaFinal" => "387" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16006002" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis, management and treatment of hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Strader D.B." 1 => "Wright T" 2 => "Thomas D.L." 3 => "Seeff LB." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20119" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2004" "volumen" => "39" "paginaInicial" => "1147" "paginaFinal" => "1171" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15057920" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interferon alpha 2b and ribavirin for patients with chronic hepatitis C and normal ALT." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:14 [ 0 => "Jacobson I.M." 1 => "Ahmed F" 2 => "Russo M.W." 3 => "Lebovics E" 4 => "Dieterich D" 5 => "Esposito S" 6 => "Bach N" 7 => "Klion F" 8 => "Tobias H" 9 => "Antignano L" 10 => "Brown R" 11 => "Gabbaizadeh D" 12 => "Geders J" 13 => "Levendoglu H." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2004.30049.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2004" "volumen" => "99" "paginaInicial" => "1700" "paginaFinal" => "1705" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15330905" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The significance of baseline serum alanine aminotransferase on pretreatment disease characteristics and response to antiviral therapy in chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Gordon S" 1 => "Fang J" 2 => "Silverman A" 3 => "McHutchinson J" 4 => "Albrecht J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2000.9321" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2000" "volumen" => "32" "paginaInicial" => "400" "paginaFinal" => "404" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10915749" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Viral clearance in HCV viraemic patients with normal alanine aminotransferase after combination therapy: a controlled open labelled study." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:12 [ 0 => "Mangia A" 1 => "Spinzi G" 2 => "Vuturo O" 3 => "Pazienza V" 4 => "Iacobellis A" 5 => "Piattelli M" 6 => "Giacobbe A" 7 => "Leandro G" 8 => "Piermanni V" 9 => "Minoli G" 10 => "Montalto G" 11 => "Andriulli A." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2004" "volumen" => "19" "paginaInicial" => "331" "paginaFinal" => "337" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14984380" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pilot study of interferon alfa and ribavirin treatment in patients with chronic hepatitis C and normal transaminase values." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Lee S" 1 => "Sherman M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2001" "volumen" => "8" "paginaInicial" => "202" "paginaFinal" => "205" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11380798" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of interferon alfa and ribavirin treatment for chronic hepatitis C in patients with normal serum aminotransferases." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Hui C.K." 1 => "Monto A" 2 => "Belaye T" 3 => "Lau E" 4 => "Wright TL." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.52.11.1644" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2003" "volumen" => "52" "paginaInicial" => "1644" "paginaFinal" => "1648" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14570736" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peginterferon alfa 2a (40 KD) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Zeuzem S" 1 => "Diago M" 2 => "Gane E" 3 => "Reddy R" 4 => "Pockros P" 5 => "Prati D" 6 => "Investigator Group" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2004" "volumen" => "127" "paginaInicial" => "1724" "paginaFinal" => "1732" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15578510" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Towards more individualised management of hepatitis C virus patients with initially or persistently normal alanine aminotransferase levels." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Alberti A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2004.12.004" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2005" "volumen" => "42" "paginaInicial" => "266" "paginaFinal" => "274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15664254" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/00000005000000S1/v1_201906280857/S1665268119319684/v1_201906280857/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/16652681/00000005000000S1/v1_201906280857/S1665268119319684/v1_201906280857/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119319684?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 0 | 2 |
| 2024 October | 9 | 2 | 11 |
| 2024 September | 11 | 2 | 13 |
| 2024 August | 14 | 3 | 17 |
| 2024 July | 23 | 5 | 28 |
| 2024 June | 13 | 4 | 17 |
| 2024 May | 13 | 2 | 15 |
| 2024 April | 19 | 2 | 21 |
| 2024 March | 29 | 4 | 33 |
| 2024 February | 21 | 2 | 23 |
| 2024 January | 8 | 5 | 13 |
| 2023 December | 4 | 1 | 5 |
| 2023 November | 6 | 4 | 10 |
| 2023 October | 4 | 5 | 9 |
| 2023 September | 2 | 0 | 2 |
| 2023 August | 11 | 1 | 12 |
| 2023 July | 3 | 1 | 4 |
| 2023 June | 13 | 6 | 19 |
| 2023 May | 31 | 1 | 32 |
| 2023 April | 40 | 2 | 42 |
| 2023 March | 22 | 0 | 22 |
| 2023 February | 22 | 1 | 23 |
| 2023 January | 3 | 5 | 8 |
| 2022 December | 4 | 2 | 6 |
| 2022 November | 3 | 3 | 6 |
| 2022 October | 6 | 6 | 12 |
| 2022 September | 5 | 6 | 11 |
| 2022 August | 7 | 5 | 12 |
| 2022 July | 6 | 6 | 12 |
| 2022 June | 3 | 5 | 8 |
| 2022 May | 5 | 5 | 10 |
| 2022 April | 10 | 6 | 16 |
| 2022 March | 5 | 9 | 14 |
| 2022 February | 4 | 2 | 6 |
| 2022 January | 6 | 4 | 10 |
| 2021 December | 6 | 12 | 18 |
| 2021 November | 3 | 8 | 11 |
| 2021 October | 8 | 8 | 16 |
| 2021 September | 4 | 6 | 10 |
| 2021 August | 7 | 7 | 14 |
| 2021 July | 6 | 5 | 11 |
| 2021 June | 5 | 5 | 10 |
| 2021 May | 5 | 8 | 13 |
| 2021 April | 16 | 10 | 26 |
| 2021 March | 2 | 5 | 7 |
| 2021 February | 2 | 6 | 8 |
| 2021 January | 3 | 10 | 13 |
| 2020 December | 8 | 5 | 13 |
| 2020 November | 4 | 4 | 8 |
| 2020 October | 4 | 3 | 7 |
| 2020 September | 4 | 2 | 6 |
| 2020 August | 6 | 4 | 10 |
| 2020 July | 2 | 1 | 3 |
| 2020 June | 3 | 2 | 5 |
| 2020 May | 4 | 6 | 10 |
| 2020 April | 1 | 0 | 1 |
| 2020 March | 4 | 1 | 5 |
| 2020 February | 2 | 0 | 2 |
| 2020 January | 2 | 4 | 6 |
| 2019 December | 6 | 3 | 9 |
| 2019 November | 2 | 0 | 2 |
| 2019 October | 1 | 0 | 1 |
| 2019 September | 0 | 2 | 2 |
| 2019 August | 1 | 1 | 2 |
| 2019 July | 2 | 1 | 3 |
| 2019 June | 2 | 7 | 9 |
Show all
