No significant correlation exists between core promoter mutations, viral replication, and liver damage in chronic hepatitis B infection

Authors

  • Yoon Keun Chun,

    1. Department of Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
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  • Jee Youn Kim,

    1. Department of Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
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  • Hong Jung Woo,

    1. East-West Medical Research Institute, Kyung Hee University, Seoul 130-701, Korea
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  • Soo Myung Oh,

    1. East-West Medical Research Institute, Kyung Hee University, Seoul 130-701, Korea
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  • Insug Kang,

    1. Department of Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
    2. East-West Medical Research Institute, Kyung Hee University, Seoul 130-701, Korea
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  • Joohun Ha,

    1. Department of Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
    2. East-West Medical Research Institute, Kyung Hee University, Seoul 130-701, Korea
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  • Sung Soo Kim

    Corresponding author
    1. Department of Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
    2. East-West Medical Research Institute, Kyung Hee University, Seoul 130-701, Korea
    • Department of Molecular Biology, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-gu, Seoul 130-701, Korea. fax: (82) 2-959-8168
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Abstract

Hepatitis B virus (HBV) core promoter mutants have been proposed to contribute to severe liver damage by increasing viral loads, but this has not yet been clearly shown. To examine the effects of core promoter mutants on viral load and liver damage, we first developed a polymerase chain reaction (PCR)-based semiquantitative HBV DNA detection method with a high sensitivity (able to detect as low as 103 molecules/mL). Then we cloned 12 predominant core promoter mutants from 41 chronic hepatitis B patients. The in vitro promoter and replication activities of these mutants were similar to those of wild-type virus. However, viral load was highly variable, and this was dependent on individual patients rather than mutant type. In addition, there was no mutant type that showed any unique correlation with alanine transaminase (ALT) levels. Viral load was not significantly correlated with ALT level in both cross-sectional and longitudinal studies. Quantitation of HBV levels also revealed no clear correlation between hepatitis B e antigen (HBeAg) status and viral load. Taken together, these results indicated that the replication activity of core promoter mutants has little effect on viral load, and that viral load does not correlate with the severity of liver damage or with HBeAg status.

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