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

被引:82
作者
Asahina, Y
Izumi, N
Enomoto, N
Uchihara, M
Kurosaki, M
Onuki, Y
Nishimura, Y
Ueda, K
Tsuchiya, K
Nakanishi, H
Kitamura, T
Miyake, S
机构
[1] Musashino Red Cross Hosp, Div Gastroenterol & Hepatol, Musashino, Tokyo 1808610, Japan
[2] Univ Yamanashi, Fac Med, Dept Internal Med 1, Yamanashi 4093898, Japan
关键词
NS5A; NS5B; ISDR; HCV; HCV dynamics;
D O I
10.1016/j.jhep.2005.05.032
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 log(10)copy/ml in response to ribavirin monotberapy (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. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:623 / 629
页数:7
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