Display Settings:

Format

Send to:

Choose Destination
J Hepatol. 2005 Oct;43(4):623-9.

Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C.

Author information

  • 1Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan.

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

PMID:
16098627
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk