Journal of Hepatology

<<<<home>>>>

Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C, 4 July 2005
Asahina Y, Izumi N, Enomoto N, Uchihara M, Kurosaki M, Onuki Y, Nishimura Y, Ueda K, Tsuchiya K, Nakanishi H, Kitamura T, Miyake S
pages 623-629
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.