Changes of HCV quasispecies during combination therapy with interferon and ribavirin
Changes of HCV quasispecies during combination therapy with interferon and ribavirin
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DOI：
10.1016/j.hepres.2004.02.014
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发表时间：
2004-06-01
影响因子：
4.2
通讯作者：
Watanabe, M
中科院分区：
文献类型：
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作者：
Ueda, E;Enomoto, N;Watanabe, M
用干扰素（IFN）和利巴韦林治疗慢性丙型肝炎病毒（HCV）感染可提高HCV根除率，但只有约13-14%的既往用IFN治疗的Ib型HCV无应答者（NR）获得持续病毒学应答（SVR）。为了确定HCV准种多样性是否与IFN和利巴韦林治疗的结果相关，我们研究了13例IFN单药治疗失败后接受IFN-α 2b和利巴韦林联合治疗的患者。在联合治疗前和治疗期间，通过克隆和测序评估HCV准种多样性。在治疗过程中，NR患者的准种多样性减少，在包膜2（E2）结构域的高变区（HVR）1和NS 5A的干扰素敏感性决定区（ISDR）。SVR和治疗结束病毒应答（ETR）患者的治疗前核苷酸准种多样性低于NR患者。对利巴韦林的耐药性与治疗前的高度异质性和HCV基因组准种的选择有关。HVR准种可能是IFN和利巴韦林联合治疗疗效的预测因子。(C)2004 Elsevier B. V.保留所有权利。
Treatment of chronic hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin improves the rate of eradication of HCV, but only about 13-14% of non-responders (NR) with HCV of genotype Ib previously treated with IFN achieve a sustained virological response (SVR). To determine whether HCV quasispecies diversity correlates with the outcome of therapy with IFN and ribavirin, we studied 13 patients undergoing combination therapy with IFN-alpha2b and ribavirin after failure of IFN monotherapy. HCV quasispecies diversity was assessed by cloning and sequencing before and during combination therapy. During therapy, quasispecies diversity diminished in NR patients, both in the hypervariable region (HVR) 1 of the envelope 2 (E2) domain and in the interferon sensitivity-determining region (ISDR) in the NS5A. Pre-treatment nucleotide quasispecies diversity was lower in SVR and end-of-therapy viral response (ETR) patients than in NR patients. Resistance to ribavirin was associated with high pre-treatment heterogeneity and the selection of quasispecies of the HCV genome. HVR quasispecies may be a predictor of efficacy of combination therapy with IFN and ribavirin. (C) 2004 Elsevier B.V. All rights reserved.