Asahina Yasuhiro, Izumi Namiki, Enomoto Nobuyuki, Uchihara Masakatsu, Kurosaki Masayuki, Onuki Yuko, Nishimura Yuki, Ueda Ken, Tsuchiya Kaoru, Nakanishi Hiroyuki, Kitamura Takatoshi, Miyake Shozo
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan.
J Hepatol. 2005 Oct;43(4):623-9. doi: 10.1016/j.jhep.2005.05.032.
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.
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.
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.
Ribavirin may act as a mutagen, and mutations occurring during ribavirin therapy correlate with the virological response to subsequent IFN/ribavirin combination therapy.
背景/目的：阐明利巴韦林在临床环境中是否作为一种诱变剂，并明确利巴韦林诱导的突变与联合治疗的病毒学反应之间的关系。
34例丙型肝炎病毒（HCV）1b基因型患者接受了4周的利巴韦林单药治疗，随后进行为期24周的干扰素/利巴韦林治疗。确定了非治疗观察期及随后利巴韦林单药治疗期间的HCV突变情况，并评估了突变与后续干扰素/利巴韦林治疗反应之间的关系。
利巴韦林单药治疗后，血清HCV水平从6.90 log10拷贝/毫升显著降至6.56 log10拷贝/毫升（P < 0.0001）。利巴韦林单药治疗期间，NS5A和NS5B区域的核苷酸突变发生率分别为2.9×10⁻²/位点/年和1.3×10⁻²/位点/年，显著高于之前非治疗观察期的突变率（分别为0.60×10⁻²/位点/年和0.24×10⁻²/位点/年，P = 0.02）。持续病毒学应答者（SVRs，n = 10）的NS5A区域突变率显著高于无应答者（分别为8.8×10⁻²/位点/年和0.38×10⁻²/位点/年，P = 0.0005）。在NS5A区域，非同义突变仅发生在SVRs中。
利巴韦林可能作为一种诱变剂，且利巴韦林治疗期间发生的突变与后续干扰素/利巴韦林联合治疗的病毒学反应相关。
