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, 43 (4), 623-9

Mutagenic Effects of Ribavirin and Response to Interferon/Ribavirin Combination Therapy in Chronic Hepatitis C

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Mutagenic Effects of Ribavirin and Response to Interferon/Ribavirin Combination Therapy in Chronic Hepatitis C

Yasuhiro Asahina et al. J Hepatol.

Abstract

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 x 10(-2)/site/year and 1.3 x 10(-2)/site/year, respectively, a significantly higher rate than the mutation rates during the prior non-treatment observation period (0.60 x 10(-2)/site/year and 0.24 x 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 x 10(-2)/site/year vs. 0.38 x 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.

Comment in

  • Mutagenic effects of ribavirin in vivo.
    Perelson AS, Ribeiro RM. Perelson AS, et al. J Hepatol. 2005 Oct;43(4):553-5. doi: 10.1016/j.jhep.2005.07.003. J Hepatol. 2005. PMID: 16099528 No abstract available.

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