Mutations in the NS5A and E2-PePHD regions of hepatitis C virus genotype 1b and response to combination therapy of interferon plus ribavirin

Background/aims: Combination therapy with interferon (IFN) and ribavirin is the current standard treatment for chronic hepatitis C, but the efficacy is still not satisfactory, especially for genotype 1b. NS5A and E2 proteins of hepatitis C virus (HCV) may repress the IFN-induced RNA-dependent protein kinase (PKR), and thus have the potential to influence the response of HCV to IFN therapy; however, this issue remains controversial. Methods: <LF>Nucleotide sequences of the PKR-eIF2alpha phosphorylation homology domain (E2-PePHD) and PKR-binding domain (NS5A-PKR bd) of the HCV genome were analyzed by amplification and direct sequencing in 30 HCV genotype 1b patients who had been treated with IFN and ribavirin. Results: Nine (30%) patients achieved a sustained virological response (SVR) to combination therapy. Pretreatment variables and amino acid substitutions were compared between responders and non-responders. The responders were younger than non-responders (37.2+/-10.4 vs. 45.4+/-9.5 years, P=0.017), whereas no significant statistical differences were found in the number of amino acid substitutions in NS5A and E2-PePHD regions between the two groups. Conclusions: Genetic heterogeneity in NS5A and E2-PePHD regions of the HCV genome may not serve as a predictor for treatment outcome with combination therapy in Taiwanese patients with chronic HCV genotype 1b infection.