Relationship between the effect of interferon therapy and the change of hepatitis C virus non-structural 5B gene

Background: Hepatitis C virus (HCV)-RNA titre has been regarded as a factor affecting the response to interferon (IFN) therapy of patients with chronic hepatitis C (CHC). The focus of our study is the investigation of the nucleotide sequence of HCV-RNA NS5B, which may code RNA-dependent RNA polymerase and NS5A in the sera of 33 patients with CHC prior to IFN therapy. Methods: Hepatitis C virus genotype and HCV-RNA titre were examined by polymerase chain reaction (PCR) and competitive reverse transcriptase-PCR. Results: The sequence for HCV-RNA NS5B (nt 8331-8600 in Ib and 8410-8679 in 2a) was determined by direct sequencing. The changes of the predicted amino acids in the genotype-specific sites of HCV-J, HCV-BK, HC-J4/83, HCV-JT, HCV-N, HC-J6 and HCV-K2a were examined, and the mutation was defined when changes of amino acids in sites specific to different reported genotypes were revealed. The mutations were observed in 6/19 (32%) in genotype Ib and 9/14 (64%) in 2a. In the Ib group, complete response (CR) was achieved in 5/6 of the mutant and in 2/13 of the wild type groups (P< 0.05). No relationship was observed between IFN effectiveness and HCV-RNA titre in the Ib wild type group. In the 2a group, CR was achieved in 4/9 of the mutant and in 4/5 of the wild type groups. An inverse relationship between IFN responsiveness and HCV-RNA titre was apparent in Ib mutant, 2a wild and 2a mutant. Conclusions: These data suggest the possible relationship between changes in the HCV-NS5B gene and the effect of IFN therapy in CHC patients with genotype 1b.