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Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients

Authors

  • L.Y. Lin,

    1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • V.W.S. Wong,

    1. Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • H.J. Zhou,

    1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • H.Y. Chan,

    1. Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • H.L. Gui,

    1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • S.M. Guo,

    1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • H. Wang,

    1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • L. Huang,

    1. Department of Infectious Diseases, No. 3 People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • S.S. Bao,

    1. Discipline of Pathology, The Bosch Institute and The School of Medical Sciences, Faculty of Medicine, The University of Sydney, Sydney, Australia
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  • Q. Xie,

    Corresponding author
    1. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    • Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin er Road, No. 197, Shanghai 200025, China.
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  • H.L.Y. Chan

    Corresponding author
    1. Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
    • Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong SAR, China.
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    • H.L.Y. Chan is an advisory board member of Novartis Pharmaceutical, Abbott Diagnostics, F. Hofmann-La Roche, and Bristol-Myers Squibb. Q. Xie is an advisory board member of Bristol-Myers Squibb. All other authors have no interests to disclose.


  • Study design, sample collection, laboratory work, data analysis, and manuscript writing were done by L.Y. Lin; V.W.S. Wong did the supervision of laboratory work and critical review of manuscript; study design and sample collection was also done by H.J. Zhou; H.Y. Chan performed the laboratory work; H.L. Gui, S.M. Guo, and H. Wang did sample collection; L. Huang did sample collection and laboratory work; S.S. Bao critically reviewed the manuscript; Q. Xie did study design, sample collection, manuscript writing, and administrative work; H.L.Y. Chan did study design, supervision of laboratory work and data analysis, manuscript writing, and administrative work.

Abstract

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/106 cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B. J. Med. Virol. 82:1494–1500, 2010. © 2010 Wiley-Liss, Inc.

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