HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin
HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin
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DOI：
10.1016/j.jhep.2004.01.019
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发表时间：
2004-05-01
影响因子：
25.7
通讯作者：
Capobianchi, MR
中科院分区：
文献类型：
--
作者：
Abbate, I;Lo Iacono, O;Capobianchi, MR
背景/目标：在基因型1b HCV慢性感染患者中研究了HVR-1准种组成和演变，用PEG-IFN α 2b或STD-IFN α 2b加RBV治疗。方法：通过计算基线、治疗4周后（T1）和随访（T18）时的核苷酸复杂性、多样性、同义（S）和非同义（NS）取代来评估HVR-1异质性。通过构建系统发育树分析病毒准种的进化。结果：未观察到基线病毒血症与异质性的相关性。核苷酸复杂性在显示早期病毒学应答的患者中较低，并且倾向于与治疗4周时的病毒载量下降呈负相关。在大多数SR中，在治疗4周期间发生了准种组成的深刻变化，而在NR中几乎没有观察到治疗前变体的重大变化。复发表明两种模式的准种进化。病毒准种随访后发现在T1在复发和NR patients.Conclusions：基线参数的HVR-1异质性似乎参与了早期反应的治疗，早期反应与深刻的变化HVR-1准种。在早期治疗压力下存活的病毒准种最有可能在T18时引起病毒反弹或持续存在。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN alpha2b or STD-IFN alpha2b plus RBV.Methods: HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees.Results: No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients.Conclusions: Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.