High diversity of hepatitis C viral quasispecies is associated with early virological response in patients undergoing antiviral therapy

Authors

  • Xiaofeng Fan,

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, MO
    2. St. Louis University Liver Center, St. Louis University School of Medicine, St. Louis, MO
    • Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, 3635 Vista Avenue, St. Louis, MO 63110
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    • fax: (314) 577-8125.

  • Qing Mao,

    1. Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
    2. Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
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  • Donghui Zhou,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, MO
    2. Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • Yang Lu,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, MO
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  • Jianwei Xing,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, MO
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  • Yanjuan Xu,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, MO
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  • Stuart C. Ray,

    1. Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
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  • Adrian M. Di Bisceglie

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, MO
    2. St. Louis University Liver Center, St. Louis University School of Medicine, St. Louis, MO
    • Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University School of Medicine, 3635 Vista Avenue, St. Louis, MO 63110
    Search for more papers by this author
    • fax: (314) 577-8125.


  • Potential conflict of interest: Dr. Di Bisceglie is a consultant for and received grants from Roche. Drs. Ray and Mao received grants from Roche.

Abstract

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. Conclusion: EVR is associated with elevated HCV QS diversity and complexity, especially in patients with significantly higher HCV genetic heterogeneity.(HEPATOLOGY 2009;50:1765–1772.)

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