Antiviral Combination Therapy With Peginterferon and Ribavirin Does not Induce a Therapeutically Resistant Mutation in the HCV Core Region Regardless of Genetic Polymorphism Near the IL28B Gene

Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
Journal of Medical Virology (Impact Factor: 2.35). 09/2011; 83(9):1559-64. DOI: 10.1002/jmv.22145
Source: PubMed


An association has been reported between genetic polymorphism near IL28B gene and the prevalence of mutation of hepatitis C virus (HCV) core region residue 70, both of which have been associated with a lack of virologic response to antiviral combination therapy with peginterferon (PEG-IFN) and ribavirin. This study investigated whether PEG-IFN/ribavirin combination therapy induces amino acid (AA) mutation at residue 70 of HCV and whether genetic polymorphism near IL28B gene affects it. AA substitutions at residue 70 of the HCV core region were measured and compared before and after combination therapy in 65 non-responders and 88 relapsers to the combination therapy. In three patients in whom both wild-type AA (arginine) and mutant-type AA (glutamine or histidine) were detected at residue 70 before treatment, only mutant-type AA was identified after treatment. In two patients who had wild-type AA solely before treatment, both wild-type and mutant-type AAs were identified at residue 70 after treatment. In five patients, in whom the AA had changed at residue 70 between before and after treatment, four patients carried the TT genotype at a polymorphic locus (rs8099917) near the IL28B gene and one carried the TG/GG genotype. No difference was found in the prevalence of this change of AA at residue 70 between the TT and the TG/GG genotype. Antiviral combination therapy with PEG-IFN and ribavirin does not appear to induce mutation of HCV core region residue 70 regardless of genetic polymorphism near the IL28B gene in Japanese patients infected with HCV genotype 1b.

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    ABSTRACT: Hepatitis C virus (HCV) is considered a significant risk factor in HCV-induced liver diseases and development of hepatocellular carcinoma (HCC). Nucleotide substitutions in the viral genome result in its diversification into quasispecies, subtypes and distinct genotypes. Different genotypes vary in their infectivity and immune response due to these nucleotide/amino acid variations. The current combination treatment for HCV infection is pegylated interferon α (PEG-IFN-α) with ribavirin, with a highly variable response rate mainly depending upon the HCV genotype. Genotypes 2 and 3 are found to respond better than genotypes 1 and 4, which are more resistant to IFN-based therapies. Different studies have been conducted worldwide to explore the basis of this difference in therapy response, which identified some putative regions in the HCV genome, especially in Core and NS5a, and to some extent in the E2 region, containing specific sequences in different genotypes that act differently with respect to the IFN response. In the review, we try to summarize the role of HCV proteins and their nucleotide sequences in association with treatment outcome in IFN-based therapy.
    Full-text · Article · Jul 2013 · Archives of Virology