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 1b 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 1b and 9/14 (64%) in 2a. In the 1b 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 1b 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 1b 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.