Abstract:Background/Aims: In hepatitis C virus-1b, it has been suggested that an amino acid stretch (aa 2209–2248) of the carboxy terminal half of the non-structural 5A (NS5A) region participates in the response to interferon treatment. 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-1b isolates in interferon response in France. Methods: We determined the NS5A sequences of 70 patients with chronic hepatitis C before IFN therapy and then compared them with HCV-J prototype sequence. 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 patients without amino acid substitutions in the NS5A (aa 2209–2248) sequence, and in the patients with HCV-J isolates. Viral load was significantly higher in the patients with no amino acid substitutions in the NS5A (aa 2209–2248) sequence. Conclusions: In HCV-1b infected patients, an HCV-J strain with no amino acid substitution in the NS5A (aa 2209–2248) region indicates a poor prognosis for response to IFN therapy. The low interferon response rate in HCV-1b infection in Europe is probably not due to a difference between isolates.