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
Source: PubMed


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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    • "Published online in Wiley Online Library (wileyonlinelibrary.com). [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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    • "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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    • "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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