High diversity of hepatitis C viral quasispecies is associated with early virological response in patients undergoing antiviral therapy.
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 show an exponential distribution pattern of intrapatient 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.


CONCLUSIONS
EVR is associated with elevated HCV QS diversity and complexity, especially in patients with significantly higher HCV genetic heterogeneity.
Fan
Xiaofeng
X
Division of Gastroenterology and Hepatology, Department of Internal Medicine, St Louis University School of Medicine, St Louis, MO, USA. fanx@slu.edu
Mao
Qing
Q
Zhou
Donghui
D
Lu
Yang
Y
Xing
Jianwei
J
Xu
Yanjuan
Y
Ray
Stuart C
SC
Di Bisceglie
Adrian M
AM
D000998:Antiviral Agents / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019562:Viral Load
D000998:Antiviral Agents