Source

Department of Advanced Medicine for Liver Diseases, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, JAPAN 4093898; First Department of Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, JAPAN 4093898. maekawa@yamanashi.ac.jp.

Abstract

To comprehensively characterize the contribution of virological factors as well as interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated-interferon plus ribavirin (PEG-IFN/RBV) therapy for chronic hepatitis C virus (HCV)-1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino acid sequence study in consecutive 103 HCV-1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding window comparison analysis to characterize response-specific viral sequences along with IL28B SNPs analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), non-early viral response (nEVR), sustained virological response (SVR) or relapse, following regions were extracted as most significantly associated with the different responses respectively: NS5A aa.2224-2248(p=1.2E-07), core aa.70 (p=4E-04), NS5A aa.2340-2382(p=7.0E-08) and NS5A aa.2360-2377(p=1.1E-05). Those NS5A regions nearly coincided with the interferon sensitivity-determining region (ISDR, NS5A aa.2209-2248) and the IFN/RBV resistance-determining region (IRRDR, NS5A aa.2339-2379). In a multivariate analysis, the IL28B SNP (OR 16.8, p=0.009) and NS5A aa.2340-2382 (OR 13.8, p=0.0003) were extracted as the two most significant independent variables contributing to the final outcome.