Number of mutations within CTL-defined epitopes of the hepatitis B Virus (HBV) core region is associated with HBV disease progression

Authors

  • Daniel Kim,

    1. Division of Infectious Diseases, University of California, San Diego, School of Medicine, La Jolla, California
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  • Kwang Soo Lyoo,

    1. Department of Internal Medicine and WHO Collaborating Center on Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul, Korea
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  • Davey Smith,

    1. Division of Infectious Diseases, University of California, San Diego, School of Medicine, La Jolla, California
    2. San Diego Veterans Affairs Medical Center, La Jolla, California
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  • Wonhee Hur,

    1. Department of Internal Medicine and WHO Collaborating Center on Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul, Korea
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  • Sung Woo Hong,

    1. Department of Internal Medicine and WHO Collaborating Center on Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul, Korea
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  • Pil Soo Sung,

    1. Department of Internal Medicine and WHO Collaborating Center on Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul, Korea
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  • Seung Kew Yoon,

    1. Department of Internal Medicine and WHO Collaborating Center on Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul, Korea
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  • Sanjay Mehta

    Corresponding author
    1. Division of Infectious Diseases, University of California, San Diego, School of Medicine, La Jolla, California
    • Division of Infectious Diseases, University of California San Diego, School of Medicine, 9500 Gilman Dr. #0711, La Jolla, CA 92093, USA.
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  • Conflict of interest: Nothing to disclose.

Abstract

The virologic determinants of progressive liver disease associated with hepatitis B virus (HBV) remain unclear. Previous investigations have associated HBV disease with specific mutations but this association may be confounded by HBV genotype, HLA haplotype of the infected individual or both. The association between non-synonymous mutations located within putative cytotoxic T-lymphocyte directed epitopes (CDE) of the HBV core region and disease states was investigated. Subjects infected with HBV were enrolled from a clinical cohort in Seoul, Korea, and HBV core gene sequences were analyzed for mutational patterns inside and outside of CDE with respect to subject demographics and HBV-related disease states. No specific mutation or pattern of mutations were associated with progressive disease states; however, individuals with cirrhosis and hepatocellular carcinoma had greater numbers of non-synonymous mutations within CDE when compared to those with chronic HBV infection who were HBeAg positive (P = 0.007 and 0.026, respectively). In conclusion, this study demonstrates that HBV disease progression is associated with viral escape mutations that are a marker of CTL activity. These data suggest that the number of non-synonymous mutations in the HBV core region may predict HBV disease progression better than any single mutation or pattern of mutations. J. Med. Virol. 83:2082–2087, 2011. © 2011 Wiley Periodicals, Inc.

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