Exploring differences in response to treatment with peginterferon alpha 2a (40kD) and ribavirin in chronic hepatitis C between genotypes 2 and 3

Department of Medicine, University of Toronto, Toronto, ON, Canada.
Journal of Viral Hepatitis (Impact Factor: 3.91). 02/2008; 15(1):52-7. DOI: 10.1111/j.1365-2893.2007.00889.x
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Chronic hepatitis C virus (HCV) infections with genotype 2 or 3 are associated with favourable sustained virologic response (SVR) rates. However, genotype 3 may respond less well. We reassessed all treatment-naive patients with genotype 2 and 3 participating in a large expanded-access, non-randomized, open-label trial, evaluating 180microg pegylated interferon (peg-IFN) alpha-2a (40kD) once weekly and 800 mg/day ribavirin for 24-48 weeks. Factors measured prior to initiation of antiviral therapy were considered in the multiple logistic regression model for predicting SVR. In total, 180 patients were analysed of which 72 (40%) were infected by genotype 2 and 108 (60%) genotype 3. The baseline characteristics between patients infected by genotype 2 or 3 were no different including the distribution of hepatic fibrosis stages by METAVIR score. Overall SVR was lower in those patients infected with genotype 3. The significant multivariate predictors of lack of SVR were hepatic fibrosis (P = 0.014) and genotype 3 (P = 0.030). The negative impact of cirrhosis (METAVIR score F4) on treatment response was more evident among subjects with genotype 3 than those with genotype 2 (P = 0.027). There is significant interaction between cirrhosis and genotype 3 leading to a poor antiviral response in such patients requiring an alternate management strategy. This finding should be confirmed in a larger population.

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Available from: Kevork Peltekian, Oct 06, 2015
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    • "Published online in Wiley Online Library ( [Powis et al., 2008; Wu et al., 2012]. This therapy may also has adverse effects and the patients often opt for discontinuation of treatment [Rosen and Gretch, 1999]. "
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    ABSTRACT: The aim of this study was to describe the genetic characteristics of Pakistani patients infected with hepatitis C virus (HCV) in relation to IL28B polymorphisms and its association to interferon and ribavirin treatment response. A total of 220 patients, infected with HCV were enrolled, out of which 100 were responders and 120 were nonresponders. The whole blood samples were collected to extract viral RNA and genomic DNA. PCR following the restriction fragment length polymorphism method was used to genotype IL28B rs12979860, rs8099917, and rs12980275 polymorphisms. Liver biopsies and HCV genotyping were performed in nonresponder patients. The rs12980275 AA genotype exhibited significant correlation to treatment response and was found in 62% of the responders and 37.5% of nonresponder patients, whereas AG genotype was noticed frequently in the nonresponder group (P < 0.0001). The rs12979860 CT and rs8099917 TT genotypes were found in 74% and 66% of the responders as compared to 58.3% and 50.8% in nonresponder patients (P = 0.001 and P = 0.032) respectively. HCV 3a genotypes were detected in 50.8% of the nonresponder patients. No significant association was detected between liver biopsy findings and IL28B SNPs (P > 0.05). The results showed the significant association of rs12980275 polymorphism with treatment response in HCV patients followed by rs12979860 and rs8099917. This is the first report describing the association of rs12980275 with response to HCV treatment from Pakistan. These findings may help in predicting the outcome of pegylated interferon and ribavirin treatment in HCV patients, and may reduce the side effects and cost of treatment in predicting non-responder patients. J. Med. Virol. © 2015 Wiley Periodicals, Inc.
    Journal of Medical Virology 02/2015; 87(5). DOI:10.1002/jmv.24100 · 2.35 Impact Factor
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    • "These would need to stratify by at least two of the major adverse factors for an SVR, fibrosis stage, and baseline viral load [3] [14], as they can significantly influence the outcome of antiviral therapy. This was shown when re-analyzing the experience of a Canadian multi-centered and non-randomized study in which the rate of SVR in G3 patients with cirrhosis was 17%, in comparison to >60% in the absence of cirrhosis [25]. The ongoing EXACT-R(3) is a randomized clinical trial exploring the benefit of an extended regimen (48-vs 24-week) of pegIFN-a2b, using weight-based RBV, with proper stratification for fibrosis and baseline viral load. "
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    ABSTRACT: Genotypes 2 and 3 (G2/G3) of hepatitis C virus have been lumped together as 'easy to treat'. As a result, guidelines recommend 24 weeks of peginterferon/ribavirin for both. However, a closer look at trials shows that these genotypes are not the same, with G2 infection proving more responsive to peginterferon. The data supporting this conclusion are presented along with possible explanations for the differences observed. Ultimately, decisions must be made about therapy. Rapid virological response (RVR) may be the best parameter predicting successful antiviral therapy. For patients with G2 infection who achieve an RVR, shortened courses of therapy are effective. In contrast, for G3 patients without an RVR, there may be benefit to extending therapy to 48 weeks; however, this requires confirmation in prospective studies. Using RVR to guide therapy may level the playing field between these 'easy to treat' genotypes.
    Journal of Hepatology 02/2011; 55(2):466-73. DOI:10.1016/j.jhep.2011.02.004 · 11.34 Impact Factor
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    • "As recently suggested, the occurrence of more severe liver damage as compared to patients of the same age infected with different genotypes may represent a negative moderator of the treatment outcome [6]. No study has yet prospectively focused on the rates of treatment success in HCV genotype 3 patients with liver cirrhosis; although the low numbers prevent us to even find a trend throughout the lower platelets count and no SVR in patients with week 4-R, low rates of SVR were shown in two cohort studies after standard duration treatment [28] [29]. In the Accelerate study as well as in North C study, differences in SVR rates were shown in patients with advanced damage treated for a standard or a short duration course [19] [30]. "
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    ABSTRACT: The benefit of individualizing treatment for patients with genotype 3 HCV infection on the basis of viral clearance at week 4 (wk4-R) has not been firmly established. Four hundred and fourteen patients received Peg-interferon alpha-2b plus 1000-1200 mg of ribavirin daily according with body weight > or <75 kg. Patients were randomized to standard 24 weeks (Std24) or to a 12 or 36 weeks variable treatment duration (Var12/36). In the variable treatment arm, patients with or without wk4-R were allocated to either 12 or 36 weeks duration. At treatment week 4, HCV RNA was undetectable in 262 patients (63.3%), 136 in the Std24, and 126 in the Var12/36 group (p=0.41). In patients with wk4-R, end-of-treatment (EOT) responses were 80.4% (CI 85.4-95.3) and 97.6% (CI 94.9-99.9) in the two arms, respectively (p=0.019). In patients without wk4-R, corresponding rates were 61.9% (50.6-73.2) and 75.3% (CI 65.9-84.6) (p=0.08). SVR was attained in 302 patients, 71.4% (CI 65.3-77.6) in the St24 group and 74.3% (CI 58.4-80.3) in the variable 12/36 arm. Among patients with wk4-R, SVR was 81.6% (CI 75.1-88.1) and 82.5% (75.9-89.1), respectively. In patients without wk4-R, SVR amounted to 52.1% (CI 40.4-63.7) and 61.7 (CI 51.1-72.3) in the two arms (p=0.25). HCV genotype 3 patients with week4-R may be treated safely with 12 weeks of therapy, provided that sufficiently high doses of ribavirin are administered. For patients still viremic at treatment week 4, SVR rates were numerically higher after 36 weeks of treatment than after the currently recommended 24 weeks.
    Journal of Hepatology 12/2010; 53(6):1000-5. DOI:10.1016/j.jhep.2010.04.042 · 11.34 Impact Factor
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