A mutation in the interferon sensitivity-determining region is associated with responsiveness to interferon-ribavirin combination therapy in chronic hepatitis patients infected with a Japan-specific subtype of hepatitis C virus genotype 1b

The interferon sensitivity-determining region (ISDR) is useful as a predictive marker of the response to interferon (IFN) therapy for chronic hepatitis patients with a Japan-specific subtype (J-type) of hepatitis C virus (HCV) genotype 1b. This marker is not useful for predicting responsiveness of a worldwide subtype (W-type) of HCV 1b, which could explain the restricted usefulness of this system only to Japan. In the present study, we examined the predictive value of the ISDR for ribavirin combination therapy. A total of 79 patients with HCV 1b comprising 35 patients with J-type and 44 patients with W-type were treated with IFN in combination with ribavirin for more than 48 weeks. Mutations in the ISDR were detected more frequently often seen in J-type HCV 1b than in W-type; however, the sustained virological response (SVR) rate for the combination therapy was similar between the two subtypes. Multivariate analysis revealed that factors associated with SVR were IFN dose and the number of amino acid substitutions in ISDR but not with subtypes J and W. The correlation between the number of substitutions in ISDR and responses to IFN-ribavirin combination therapy was restricted to patients with J-type HCV 1b. The ISDR is a useful predictive marker for response to IFN-ribavirin combination therapy in J-type HCV.