Acute hepatitis C treatment
Paulo Roberto Lerias de Almeida
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* Secretaria Estadual de Saúde do Rio Grande do Sul, Brazil; Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil.
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"documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9 Supl 1:S112-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 57 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 16 "PDF" => 31 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Insulin resistance, hepatic steatosis and hepatitis C: A complex relationship with relevant clinical implications" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S112" "paginaFinal" => "S118" ] ] "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" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 1:</span></span>" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 911 "Ancho" => 1000 "Tamanyo" => 104275 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Relationships between metabolic and viral factors and hepatic steatosis in the setting of chronic hepatitis C. Insulin resistance is the major determinant of steatosis and in turn is aggravated by several genotype-independent mechanisms probably related to the presence of viral proteins in the hepatocyte and due to the inflammatory response linked to viral infection. Several specific steatogenic mechanisms operate in genotype 3 infection. Alcohol consumption can also contribute to steatosis development.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Marco Arrese, Arnoldo Riquelme, Alejandro Soza" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Marco" "apellidos" => "Arrese" ] 1 => array:2 [ "nombre" => "Arnoldo" "apellidos" => "Riquelme" ] 2 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Soza" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317351?idApp=UINPBA00004N" "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317351/v1_201906221034/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119317338" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31733-8" "estado" => "S300" "fechaPublicacion" => "2010-01-01" "aid" => "71395" "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:S103-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 55 "formatos" => array:3 [ "EPUB" => 16 "HTML" => 17 "PDF" => 22 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Treatment of HCV infected patients and renal disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S103" "paginaFinal" => "S106" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "David Kershenobich" "autores" => array:1 [ 0 => array:2 [ "nombre" => "David" "apellidos" => "Kershenobich" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317338?idApp=UINPBA00004N" "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317338/v1_201906221034/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Acute hepatitis C treatment" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S107" "paginaFinal" => "S111" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Paulo Roberto Lerias de Almeida" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Paulo Roberto" "apellidos" => "Lerias de Almeida" "email" => array:1 [ 0 => "paulorlalmeida@terra.com.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Secretaria Estadual de Saúde do Rio Grande do Sul, Brazil; Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil." "etiqueta" => "*" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 1.</span></span>" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 495 "Ancho" => 1019 "Tamanyo" => 60493 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Outcome of HCV infection.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Since the 1990s there has been a decline in the incidence of AHC infection in the USA and Europe and this falling incidence is attributed to improved blood donor screening, needle exchange programs and education among injection drug users. Nevertheless, others modes of transmission, including needle-stick injuries among health-care workers, sexual and perinatal transmission have gained importance. Also, unsafe medical practices and contaminated equipments have been identified as major risk factors in areas of high prevalence in developing world.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Recent surveillances for acute viral hepatitis was reported by United States Centers for Disease Control and Prevention (CDC), comparing cases in 2006/2007 with those from previous years.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> AHC declined from 2.5 to 0.3 cases/100.000 population (88%) since the ninety’s; however, since 2003 rates have plateaued and injection-drug use was the most common risk factor.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Clinical Features</span><p id="p0015" class="elsevierStylePara elsevierViewall">AHC infection is asymptomatic in most patients and only 10-20% of patients were believed to develop jaundice.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In patients in whom symptoms are developing, the incubation period between exposure and appearance of symptoms can range from 2 to 12 weeks.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Since AHC is encountered infrequently, there are only limited data on the incidence of these symptoms.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> European studies<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> of AHC at tertiary referral centers report high frequencies of symptoms including jaundice(71%), influenza-like illness(64%), dark urine and clay colored stools(36%), nausea or vomiting(35%), and pain in the right upper quadrant of the abdomen(26%). However, these studies could be affected by referral bias, since they were designed to identify HCV infection from a cohort of symptomatic patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Nevertheless, recent papers from France<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and Bulgaria<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> revealed the presence of jaundice in 40% and 70% of large series of 126 and 178 AHC infections, respectively. Other series from Japan,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Egypt<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and the USA<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> that have prospecti-vely followed injection drug users or people with needle-stick injury have reported a lower incidence of symptoms, including jaundice (0-10%), and could be more indicative of the overall scenario.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Diagnosis</span><p id="p0020" class="elsevierStylePara elsevierViewall">There is no definitive test to diagnose AHC. An identifiable exposure to HCV, recent seroconver-sion, marked increases in aminotransferases and exclusion of other causes of acute liver diseases are usually used as circumstantial evidence of AHC. The only method to conclusively diagnose AHC infection is to document seroconversion in a previously seronegative individual. This is most frequently documented in the setting of needle-stick exposure, when the exposed individual is followed prospective-ly, or during surveillance of high-risk individuals.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">After exposure, there is a window of 1-3 weeks before serum HCV-RNA can be detected in serum and it is the first evidence of HCV infection.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In older series,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> this window could be up to eight weeks, probably related to less sensitive methods for detection of HCV RNA.</p><p id="p0030" class="elsevierStylePara elsevierViewall">Serum aminotransferases become elevated approximately 4-12 weeks after exposure (range 1 to 26), with variable levels that can include significantly elevated ALT levels (> 10-20 x ULN).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">Anti-HCV ELISA tests become positive 4-10 weeks after exposure to HCV.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Detection of anti-HCV is an unreliable way to identify AHC infection, since the absence of antibodies does not preclude infection in the acute setting: the appearance of antibodies against HCV could be delayed in as many as 30-50% of patients at the onset of symptoms, particularly in immunocompromissed hosts.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Spontaneous Resolution X Development of Chronicity</span><p id="p0040" class="elsevierStylePara elsevierViewall">Early studies found that spontaneous virological clearance occurred in about 15-25% of persons who developed transfusion associated AHC and that HCV infection persisted in 75-85%; later, a far higher rate of spontaneous resolution was noted among infected children, young women and even some persons with community-acquired hepatitis C, the figures ranging between 42 and 45%.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Even higher rates of spontaneous HCV RNA clearance have been described, as observed on studies of Hofer et al (67%)<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and Gerlach, <span class="elsevierStyleItalic">et al.</span> (52%).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">As a general rule, most patients with AHC who are destined to spontaneously clear HCV viremia do so within 12 weeks and usually no later than 20 weeks after the onset of symptoms.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> If viremia persists for more than 6 months, chronic disease should be considered. The possible outcomes of AHC infection are shown in <a class="elsevierStyleCrossRef" href="#f0005">figure 1</a> and are dependent on many host and viral factors.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Two German studies suggest that patients who develop symptomatic disease tend to have a higher spontaneous resolution, 52%<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and 67%.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The presence of jaundice might be an indicator of an effective host immune response that leads to spontaneous viral clearance, although this association is not uni-form. Others factors that might contribute to spontaneous clearance include genotype 3, female gender, low viral load, white ethnic origin and rapid decline in viral load within the first 4 weeks of diagnosis. By contrast, black ethnic origin, co-existent HIV infection and advanced age could lead to viral persistence.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Treatment</span><p id="p0050" class="elsevierStylePara elsevierViewall">The published studies of AHC show considerable heterogeneity. Most studies are open-label non-comparative investigations with small patient populations that differ widely with respect to design, patient characteristics and treatment regimens; therefore, discerning the most effective intervention remains difficult.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> There is a remarkable consistency in the superiority of treatment of AHC in preventing evolution to chronic HCV infection when compared to observation. Two meta-analyses have demonstrated this profit.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Alberti et al examined the outcome of 369 treated and 201 untreated patients of 17 studies;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> the pooled data showed a sustained virolo-gic response (SVR) rate of 62% in the treated group x 12% of spontaneous clearance (p < 0.05) between untreated individuals. Licata et al.,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> examined 12 cohort studies reporting data from 162 treated and 81 untreated patients, and found that the likelihood of SVR was 70.5% in the treated compared with 35.3% in the untreated group (p < 0.05). Recent published meta-analysis<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> including 1075 patients of 22 studies confirms the evidence: SVR rates for treated patients were 78%, significantly higher than 55.1% of spontaneous clearance rates in the untreated patients (OR=3.08).</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Optimal timing of treatment</span><p id="p0055" class="elsevierStylePara elsevierViewall">Early study by Jaeckel, <span class="elsevierStyleItalic">et al.</span>,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> with standard interferon (IFN) recommended immediate therapy for AHC because of excellent treatment responses: SVR 98%; the average time from first signs and symptoms until the start of therapy were 35 days. Waiting some weeks did not reduce the SVR rates as shown by Italian study of Santantonio et al: 28 patients with AHC were followed, 11(39%) had spontaneous clearance and 15 of 16 (98%) patients who failed to spontaneously clear HCV RNA after12 weeks responded to treatment.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="p0060" class="elsevierStylePara elsevierViewall">This strategy was also examined in 129 patients<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> with AHC without spontaneously clearance by week 8, by randomized them to begin treatment at week 8, 12 or 20 (43 patients in each group): the SVR was 95%, 93% and 77% when treatment was initiated at week 8, 12 and 20, respectively. Authors suggested that the optimal time to initiate therapy might be week 12, because the response rate dropped off sharply in the group that initiated treatment at week 20. However, in genotype 1 patients the highest SVR was achieved when therapy was started at week 8 (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>); these observation need to be further in-vestigated because all treatments in the current study was administered for 12 weeks.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Also, Japanese investigators compared the SVR achieved with early initiation of treatment (8 weeks after disease onset) with a delayed treatment strategy (1 year) and demonstrated that the postponed therapy is clearly less effective: 87% and 40% of SVR, respectively.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0065" class="elsevierStylePara elsevierViewall">These studies showed that delaying treatment for 3 months from the time of diagnosis does not have a negative effect on SVR rates, at least in genotypes 2 and 3 patients, and avoids unnecessary treatment for those patients who may undergo spontaneous viral clearance.</p><p id="p0070" class="elsevierStylePara elsevierViewall">There are limited data on the optimal timing for treatment for asymptomatic patients, and it may not be unreasonable to offer immediate treatment to them, because they are less likely to clear the virus spontaneously.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Optimal duration and schedules of treatment (<a class="elsevierStyleCrossRef" href="#f0015">Figures 3</a> and <a class="elsevierStyleCrossRef" href="#f0020">4</a>)</span><p id="p0075" class="elsevierStylePara elsevierViewall">) Some meta-analyses summarized the results of several small clinical trials of AHC treatment with conventional interferon (IFN), which typically used 3-6 MU administered three times weekly for variable periods of 4-24 weeks. Overall, a modest SVR of 3252% were obtained <a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>).</p><elsevierMultimedia ident="f0015"></elsevierMultimedia><elsevierMultimedia ident="f0020"></elsevierMultimedia><p id="p0080" class="elsevierStylePara elsevierViewall">SVR rates increased with higher weekly doses of IFN. The remarkable study of Jaeckel, <span class="elsevierStyleItalic">et al.</span>,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> using an induction regimen of IFN (5 MU/day for 4 weeks, followed by 5 MU three times weekly for another 20 weeks) attained SVR in 43/44 (98%) patients. Shorter treatment durations and high-dose IFN was evaluated by others studies. In two of them, SVR was reported in 21/28(75%) patients receiving 5 MU/day for 8 weeks<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and in 20/ 24(83%) patients treated with 10 MU/day until normalization of ALT levels.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In a separate study, Nomura et al suggest that a shorter course of daily human lymphoblastoid IFN for 4 weeks could be highly efficacious, with 87% of SVR<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>).</p><p id="p0085" class="elsevierStylePara elsevierViewall">In AHC patients treated with pegylated interfe-ron (PEG-IFN), different strategies have been explored to optimize the SVR (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>). The earlier studies with PEG-IFN also used 24 weeks of treatment: in a large multicenter German study using PEG-IFN alfa-2b conducted by Wiegand et al, 89 patients were treated after a median time from symptoms to therapy of 27 days with the standard dosage of 1.5 μg/kg/wk and demonstrated a SVR of 71%;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> a smaller Swiss study reveal a scarcely SVR of 57% in a group of 14 patients that started treatment between 1 and 50 weeks after the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Both studies demonstrated poor adherence with high rates of dropout among intravenous drug users. In contrast, another 24 weeks treatment with PEG-IFN alfa-2b (1.5 μg/kg/ wk) by Santantonio et al observe a SVR in 15/ 16(94%) patients that initiate treatment 12 weeks after the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="p0090" class="elsevierStylePara elsevierViewall">Regarding treatment duration, more recent trials have evaluated the efficacy of a short, 12-week course of PEG-IFN.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Two Italian studies(32,33) use PEG-IFN alfa-2b (1.0-1.6 μg/kg/ wk) within a median time of 13.5-31 days after diagnosis. SVR was attained in 72-74% of patients, and higher rates of SVR (83-92%) were attained by patients receiving higher dosages (> 1.33 and > 1.2 μg/kg/wk).</p><p id="p0095" class="elsevierStylePara elsevierViewall">In the only randomized controlled trial<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> conducted to date, one study compared different durations of therapy in 102 patients with AHC who still had detectable HCV RNA after 8-12 weeks of observation; the patients were randomly assigned to receive PEG-IFN alfa-2b (1.5μg/kg/wk) for 8,12 or 24 weeks. Overall SVR rates were 68%, 82% and 91%, respectively. Treatment for 8 or 12 weeks was effective in genotypes 2, 3, and 4, whereas genotype 1 required 24 weeks of therapy. Multivariate analysis showed that the presence of symptoms, genotype non-1, and rapid virologic response at week 4 were associated with improved viral clearance.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Combination with ribavirin (RBV)</span><p id="p0100" class="elsevierStylePara elsevierViewall">The combination of interferons with RBV has not been tested extensively. The few studies that used RBV associated with IFN<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> or PEG-IFN<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> found it to be well tolerated, but responses rates were nor significantly higher than with monotherapy.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Treatment of Human Immunodeficiency Virus (HIV) co-infected patients</span><p id="p0105" class="elsevierStylePara elsevierViewall">HIV-infected patients exposed to HCV are less likely to clear the acute infection. Just only 4% and 5% of spontaneous resolution were observed in two more recent series of 25 and 55 co-infected pa-tients.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> There have been few small single center trials of AHC in HIV patients receiving IFN or PEG-IFN, with or without RBV; SVR rates were variable and in general lower than that seen in the HCV mono-infected patients: 0% -71%.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> A more re-cent Australian trial with 22 patients treated with PEG-IFN alfa-2a and RBV for 24 weeks showed a SVR of 80%.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="p0110" class="elsevierStylePara elsevierViewall">The identification of acute HCV infection represents a unique window of opportunity for achieving high rates of viral clearance. Treatment of AHC with different interferons offers the opportunity of SVR in excess of 90%. A waiting period for observation of 12 weeks is recommended for patients with symptomatic hepatitis to allow for spontaneous viral clearance that can occur at high rates in this subgroup. Asymptomatic and HIV patients may be treated immediately as they are less likely to undergo spontaneous clearance. Treatment durations could vary from 12 to 24 weeks, but recent data on 12 weeks of treatment are encouraging, especially in those who achieve RVR. The role of RBV has yet to be established.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1210324" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1126741" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical Features" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Diagnosis" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Spontaneous Resolution X Development of Chronicity" ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Treatment" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Optimal timing of treatment" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Optimal duration and schedules of treatment (Figures 3 and 4)" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Combination with ribavirin (RBV)" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Treatment of Human Immunodeficiency Virus (HIV) co-infected patients" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-03-20" "fechaAceptado" => "2010-04-20" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1126741" "palabras" => array:5 [ 0 => "Acute hepatitis C" 1 => "Hepatitis C virus" 2 => "Antiviral therapy" 3 => "Interferon alfa" 4 => "Pegylated interferon alfa" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">There are no well established treatment guidelines about acute hepatitis C (AHC), leaving physicians to make several challenging decisions, such whether to treat, when to treat and what treatment regimens to use. This article examines the diagnosis of acute infection and critically appraises the various treatment regimens.</p></span>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 1.</span></span>" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 495 "Ancho" => 1019 "Tamanyo" => 60493 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Outcome of HCV infection.</p>" ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 2.</span></span>" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 844 "Ancho" => 1005 "Tamanyo" => 107636 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Impact of onset of therapy on SVR, according genotypes.</p>" ] ] 2 => array:7 [ "identificador" => "f0015" "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 3.</span></span>" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 939 "Ancho" => 1005 "Tamanyo" => 134595 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">SVR according standard or induction doses regimens of IFN.</p>" ] ] 3 => array:7 [ "identificador" => "f0020" "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 4.</span></span>" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 983 "Ancho" => 974 "Tamanyo" => 193625 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">SVR with PEG-IFN for 12 or 24 weeks.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:41 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 0 | 10 |
| 2024 October | 90 | 9 | 99 |
| 2024 September | 113 | 7 | 120 |
| 2024 August | 57 | 7 | 64 |
| 2024 July | 87 | 9 | 96 |
| 2024 June | 83 | 5 | 88 |
| 2024 May | 119 | 32 | 151 |
| 2024 April | 88 | 7 | 95 |
| 2024 March | 112 | 13 | 125 |
| 2024 February | 99 | 14 | 113 |
| 2024 January | 139 | 10 | 149 |
| 2023 December | 117 | 12 | 129 |
| 2023 November | 97 | 14 | 111 |
| 2023 October | 138 | 12 | 150 |
| 2023 September | 84 | 6 | 90 |
| 2023 August | 76 | 8 | 84 |
| 2023 July | 76 | 5 | 81 |
| 2023 June | 74 | 7 | 81 |
| 2023 May | 78 | 7 | 85 |
| 2023 April | 56 | 8 | 64 |
| 2023 March | 55 | 2 | 57 |
| 2023 February | 63 | 5 | 68 |
| 2023 January | 64 | 7 | 71 |
| 2022 December | 74 | 8 | 82 |
| 2022 November | 72 | 6 | 78 |
| 2022 October | 50 | 14 | 64 |
| 2022 September | 65 | 24 | 89 |
| 2022 August | 62 | 9 | 71 |
| 2022 July | 42 | 9 | 51 |
| 2022 June | 65 | 14 | 79 |
| 2022 May | 62 | 13 | 75 |
| 2022 April | 82 | 16 | 98 |
| 2022 March | 86 | 12 | 98 |
| 2022 February | 108 | 12 | 120 |
| 2022 January | 97 | 4 | 101 |
| 2021 December | 88 | 14 | 102 |
| 2021 November | 49 | 7 | 56 |
| 2021 October | 82 | 16 | 98 |
| 2021 September | 51 | 16 | 67 |
| 2021 August | 30 | 9 | 39 |
| 2021 July | 11 | 6 | 17 |
| 2021 June | 8 | 12 | 20 |
| 2021 May | 15 | 8 | 23 |
| 2021 April | 24 | 2 | 26 |
| 2021 March | 12 | 2 | 14 |
| 2021 February | 5 | 5 | 10 |
| 2021 January | 6 | 3 | 9 |
| 2020 December | 4 | 5 | 9 |
| 2020 November | 3 | 4 | 7 |
| 2020 October | 7 | 3 | 10 |
| 2020 September | 5 | 3 | 8 |
| 2020 August | 7 | 3 | 10 |
| 2020 July | 4 | 1 | 5 |
| 2020 June | 2 | 3 | 5 |
| 2020 May | 8 | 4 | 12 |
| 2020 April | 2 | 1 | 3 |
| 2020 March | 2 | 3 | 5 |
| 2020 February | 3 | 3 | 6 |
| 2020 January | 4 | 4 | 8 |
| 2019 December | 7 | 5 | 12 |
| 2019 November | 0 | 1 | 1 |
| 2019 October | 0 | 0 | 0 |
| 2019 September | 1 | 1 | 2 |
| 2019 August | 1 | 1 | 2 |
| 2019 July | 2 | 4 | 6 |
| 2019 June | 1 | 5 | 6 |
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