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Background/Aims: To elucidate whether ribavirin acts as a mutagen in the clinical setting and to clarify the relationship between ribavirin-induced mutations and virological response to combined therapy. Methods: Thirty-four patients with hepatitis C virus (HCV) genotype 1b received ribavirin monotherapy for 4 weeks, followed by a 24-week course of IFN/ribavirin therapy. HCV mutations during a non-treatment observation period and during subsequent ribavirin monotherapy were determined, and the relationship between mutations and response to subsequent IFN/ribavirin therapy was evaluated. Results: Serum HCV significantly decreased from 6.90 to 6.56 log10copy/ml in response to ribavirin monotherapy (P < 0.0001). Nucleotide mutations in the NS5A and NS5B regions occurred during ribavirin monotherapy at a rate of 2.9× 10- 2/site/year and 1.3× 10- 2/site/year, respectively, a significantly higher rate than the mutation rates during the prior non-treatment observation period (0.60× 10- 2/site/year and 0.24× 10- 2/site/year, P = 0.02, respectively). Mutation rates in the NS5A region were significantly higher in sustained viral responders (SVRs, n = 10) than in non-responders (8.8× 10- 2/site/year vs. 0.38× 10- 2/site/year, P = 0.0005, respectively). In the NS5A region, non-synonymous mutations only occurred in SVRs. Conclusions: Ribavirin may act as a mutagen, and mutations occurring during ribavirin therapy correlate with the virological response to subsequent IFN/ribavirin combination therapy.
Background / Aims: To elucidate whether ribavirin acts as a mutagen in the clinical setting and to clarify the relationship between ribavirin-induced mutations and virological response to combined therapy. Methods: Thirty-four patients with hepatitis C virus (HCV) genotype 1b received ribavirin monotherapy for 4 weeks followed by a 24-week course of IFN / ribavirin therapy. The HCV mutations during a non-treatment observation period and during subsequent ribavirin monotherapy were determined, and the relationship between mutations and response to subsequent IFN / ribavirin therapy was evaluated Results: Serum HCV significantly decreased from 6.90 to 6.56 log10 copy / ml in response to ribavirin monotherapy (P <0.0001). Nucleotide mutations in the NS5A and NS5B regions during ribavirin monotherapy at a rate of 2.9 × 10-2 / site / year and 1.3 × 10-2 / site / year, respectively, a significantly higher rate than the mutation rates during the prior non-treatment observation period (0.60 × 10 -2 / s Mutation rates in the NS5A region were significantly higher than sustained response (SVRs, n = 10) than in non-responders (8.8 × 10 / day and 0.24 × 10-2 / site / year, P = 0.02, respectively) - 2 / site / year vs. 0.38 × 10-2 / site / year, P = 0.0005, respectively). In the NS5A region, non-synonymous mutations only occurred in SVRs. Conclusions: Ribavirin may act as a mutagen, and mutations of during ribavirin therapy correlate with the virological response to subsequent IFN / ribavirin combination therapy.