High diversity of hepatitis C viral quasispecies is associated with early virological response in patients undergoing antiviral therapy.
High diversity of hepatitis C viral quasispecies is associated with early virological response in patients undergoing antiviral therapy.
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DOI：
10.1002/hep.23290
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发表时间：
2009-12
期刊：
影响因子：
13.5
通讯作者：
Di Bisceglie, Adrian M.
中科院分区：
文献类型：
--
作者：
Fan, Xiaofeng;Mao, Qing;Zhou, Donghui;Lu, Yang;Xing, Jianwei;Xu, Yanjuan;Ray, Stuart C.;Di Bisceglie, Adrian M.
Differential response patterns to optimal antiviral therapy, peginterferon alpha plus ribavirin, are well documented in patients with chronic hepatitis C virus (HCV) infection. Among many factors that may affect therapeutic efficiency, HCV quasispecies (QS) characteristics have been a major focus of previous studies, yielding conflicting results. To obtain a comprehensive understanding of the role of HCV QS in antiviral therapy, we performed the largest-ever HCV QS analysis in 153 patients infected with HCV genotype 1 strains. A total of 4,314 viral clones spanning hypervarible region 1 were produced from these patients during the first 12 weeks of therapy, followed by detailed genetic analyses. Our data showed an exponential distribution pattern of intra-patient QS diversity in this study population in which most patients (63%) had small QS diversity with genetic distance (d) less than 0.2. The group of patients with genetic distance located in the decay region (d>0.53) had a significantly higher early virologic response (EVR) rate (89.5%), which contributed substantially to the overall association between EVR and increased baseline QS diversity. In addition, EVR was linked to a clustered evolutionary pattern in terms of QS dynamic changes. EVR is associated with elevated HCV QS diversity and complexity, especially in patients with significantly higher HCV genetic heterogeneity.
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