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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.

Yen YH, Hung CH, Hu TH, Chen CH, Wu CM, Wang JH, Lu SN, Lee CM

Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.

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 alpha-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 >or=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 >or=4 and ribavirin >or=14 mg/kg/day were independent predictors of SVR. CONCLUSION: Mutations of the ISDR correlate with SVR to Peg interferon alpha-2b plus ribavirin therapy in HCV-1b patients.

Published 13 December 2007 in Aliment Pharmacol Ther, 27(1): 72-9.
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