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Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C.
- Source :
-
Journal of hepatology [J Hepatol] 2005 Oct; Vol. 43 (4), pp. 623-9. - Publication Year :
- 2005
-
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.<br />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.<br />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.<br />Conclusions: Ribavirin may act as a mutagen, and mutations occurring during ribavirin therapy correlate with the virological response to subsequent IFN/ribavirin combination therapy.
- Subjects :
- Amino Acid Sequence
Antiviral Agents pharmacology
Base Sequence
Drug Therapy, Combination
Female
Genotype
Hepacivirus drug effects
Hepatitis C, Chronic blood
Humans
Liver pathology
Male
Middle Aged
Molecular Sequence Data
Mutation
Viral Load
Hepacivirus genetics
Hepatitis C, Chronic drug therapy
Interferon-alpha therapeutic use
Mutagens
Ribavirin pharmacology
Ribavirin therapeutic use
Viral Nonstructural Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0168-8278
- Volume :
- 43
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 16098627
- Full Text :
- https://doi.org/10.1016/j.jhep.2005.05.032