Hepatitis B virus DNA levels and outcomes in chronic hepatitis B


  • Chien-Jen Chen,

    Corresponding author
    1. Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
    2. Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
    • Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan
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    • fax: +886-2-27898784

  • Hwai-I Yang,

    1. Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
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  • Uchenna H. Iloeje,

    1. Global Epidemiology and Outcomes Research, Pharmaceutical Research Institute, Bristol-Myers Squibb Co., Wallingford, CT
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  • The REVEAL-HBV Study Group

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    • Other members of the REVEAL-HBV (Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer HBV) Study Group are listed in the Acknowledgment

  • Potential conflict of interest: Dr. Iloeje is employed by Bristol-Myers Squibb Co. A grant was provided by Bristol-Myers Squibb to Dr. Chen for conducting the laboratory tests for this study. The other authors declare that they have no potential conflicts of interest.

  • Role of the Sponsors: Dr. Iloeje (employed by Bristol-Myers Squibb) was involved in the study design, development of the analysis plan, and interpretation of the data and writing of the report. All data handling was done by the staff at the Academia Sinica and National Taiwan University. At no time did the funding sources have access to the data. The corresponding author had final responsibility for the decision to submit for publication.


Serum hepatitis B virus (HBV) DNA levels can fluctuate markedly during the course of chronic HBV infection. Both case-control and cohort studies have shown a significant, dose-response association between serum HBV DNA levels measured at the time of initial evaluation and the subsequent risk of cirrhosis. A similar direct relationship has been shown for the risk of hepatocellular carcinoma (HCC) in cross-sectional, case-control, and cohort studies. Interventional studies have shown a strong correlation between the indices of disease activity seen on liver biopsy and levels of serum HBV DNA. These studies have also shown that reduction in HBV DNA levels correlate strongly with improvements in liver histology. For patients with HCC, prognosis (including risk of death, metastasis, and recurrence following surgery) is worse with higher serum HBV DNA levels. The preponderance of the evidence in the published literature demonstrates that serum HBV DNA level is an important and independent risk factor for disease progression in chronic hepatitis B. The relative importance of serial HBV DNA measurements, the loss of hepatitis B e and surface antigens, as well as the emergence of HBV mutants in the progression of chronic hepatitis B, especially in young patients, is an important need for future research. (HEPATOLOGY 2009;49:S72–S84.)