Abstract

3a affect the response to pegylated-interferon-alpha 2b and ribavirin combination therapy. METHODS: Six hundred sixty-five patients with chronic hepatitis C were enrolled. There were 375 men and 290 women (mean age, 57.7 ± 13.5 years). HCV genotypes 1a (N = 18), 1b (N = 428), 2a (N = 137), 2b (N = 71), and 3a (N = 11) were detected. The NS5A region (IFN sensitivity-determining region (ISDR)) in each genotype was examined by direct sequencing. The proto-type for each genotype were defined and the counting the number of mutations to the sequence of proto-type in the ISDR and the strains which have more than two mutations were defined as mutant-type. Detection of the SNP of IL28B (rs8099917) was done by a real-time PCR system with specific probes. Patients received pegylated-IFNalpha 2b once each week plus oral ribavirin daily for 24 -72weeks. RESULTS: Of the 665 patients, 365 (54.9%) showed sustained virologic response (SVR). SVR rates according genotype 1a, 1b, 2a, 2b, and 3a were 44.4, 43.6, 72.9, 70.4, and 80.1%, respectively. Factors related to SVR in genotype 1a were IL28B TT allele (p=0.0359) and ISDR mutanttype (p=0.0229). The IL28B and mutation in the ISDR were the factors related to SVR on multivariate analysis in patients with genotype1b. The best SVR was achieved in patients with mutant-type ISDR and IL28B T allele (70.5%), and the worst was achieved in patients with wild-type ISDR and IL28B G allele (11.1%) in genotype 1a and 1b. Of the 137 patients, 100 (72.9%) achieved SVR in patients with genotype 2a. SVR was achieved in 65.5% of patients with wild-type ISDR and 86% of patients with mutant-type (p = 0.0097). Achievement of SVR occurred in patients with T allele (66.7%) and those with G allele (74.8%). There were no significant differences in SVR according to IL28B in genotype 2a. Similar results were found in genotype 2b. Both ISDR and IL28B in patients with genotype 3a were not associated with SVR. CONCLUSIONS: Both ISDR and IL28B were significantly associated with SVR in genotype 1a and 1b. Only ISDR was useful for predicting the IFN response in genotype 2a and 2b. The impact of ISDR and IL28B on SVR was different in each genotype and these concepts should consider in choosing optimal therapy.

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