Mutations in the interferon sensitivity-determining region (nonstructural 5A amino acid 2209-2248) in patients with hepatitis C-1b infection and correlating response to combined therapy of pegylated interferon and ribavirin

Background: Most reports suggest that mutations in the interferon sensitivity-determining region (ISDR) correlate with response to conventional interferon-based therapies in hepatitis C virus-1b (HCV-1b) patients. However, the correlation between ISDR region mutations and response to pegylated interferon plus ribavirin therapy in HCV-1b patients remains unclear. Aim: To assess whether ISDR mutations correlate with response to Peg interferon plus ribavirin therapy in HCV-1b patients. Patients and methods: Sixty HCV-1b naive patients who had undergone 6 months of Peg interferon α-2b plus ribavirin and a 6-month follow-up were enrolled. The amino acid sequences of the nonstructural 5A-interferon-induced RNA-dependent protein kinase (NS5A-PKR)-binding domain were determined by polymerase chain reaction and sequencing. Results: Thirty (50%) patients achieved sustained virological response (SVR). Univariate analysis showed that the proportion of patients with ISDR mutations ≥4 and rapid virological response rate was higher in the sustained virological response group than in the non-SVR group. Viral load was lower in the SVR group than in the non-SVR group. Multivariate analysis revealed that ISDR mutations ≥4 and ribavirin ≥14 mg/kg/day were independent predictors of SVR. Conclusion: Mutations of the ISDR correlate with SVR to Peg interferon α-2b plus ribavirin therapy in HCV-1b patients. © 2008 The Authors.