Integrity of the NS5A (amino acid 2209 to 2248) region in hepatitis C virus 1b patients non-responsive to interferon therapy

Background/Aims: In hepatitis C virus-1b, it has been suggested that an ami no acid stretch (aa 2209-2248) of the carboxy terminal half of the non-stru ctural 5A (NS5A) region participates in the response to interferon treatmen t. We tested the hypothesis that absence of mutations in the NS5A (aa 2209- 2248) sequence is required for interferon resistance. We also investigated the importance of different HCV-lb isolates in interferon response in Franc e. Methods: We determined the NS5A sequences of 70 patients with chronic he patitis C before IFN therapy and then compared them with HCV-J prototype se quence. The isolates were determined by NS5B sequencing, the "gold standard " method for genotyping and subtyping. Pre-therapeutic viral load was also measured. Results: No sustained virological response was observed in the pa tients without amino acid substitutions in the NS5A (aa 2209-2248) sequence , and in the patients with HCV-J isolates. Viral load was significantly hig her in the patients with no amino acid substitutions in the NS5A (aa 2209-2 248) sequence. Conclusions: In HCV-1b infected patients, an HCV-J strain wi th no amino acid substitution in the NSSA (aa 2209-2248) region indicates a poor prognosis for response to IFN therapy. The low interferon response ra te in HCV-1b infection in Europe is probably not due to a difference betwee n isolates.