Determinants of spontaneous surface antigen loss in hepatitis B e antigen–negative patients with a low viral load

Authors

  • Tai-Chung Tseng,

    1. Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, Taipei, Taiwan
    2. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. School of Medicine, Tzu Chi University, Hualien, Taiwan
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  • Chun-Jen Liu,

    1. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Hung-Chih Yang,

    1. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Department of Microbiology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
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  • Tung-Hung Su,

    1. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Chia-Chi Wang,

    1. Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, Taipei, Taiwan
    2. School of Medicine, Tzu Chi University, Hualien, Taiwan
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  • Chi-Ling Chen,

    1. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Stephanie Fang-Tzu Kuo,

    1. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
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  • Chen-Hua Liu,

    1. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Pei-Jer Chen,

    1. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Ding-Shinn Chen,

    1. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Jia-Horng Kao

    Corresponding author
    1. Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
    4. Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
    • Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan
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    • fax: 886-2-23825962


  • Potential conflict of interest: Nothing to report.

  • This work was supported by grants from the Buddhist Tzu-Chi General Hospital Taipei Branch (TCRD-TPE-100-C1-3), the National Taiwan University Hospital (NTUH100-S1534), the Department of Heath (DOH99-DC-1001 and DOH100-DC-1019), and the National Science Council, Executive Yuan, Taiwan (NSC99-3112-B002-023 and NSC100-3112-B002-015).

Abstract

Loss of hepatitis B surface antigen (HBsAg) usually indicates the cure of hepatitis B virus (HBV) infection. In spontaneous hepatitis B e antigen (HBeAg) seroconverters, lower serum HBsAg and HBV DNA levels have been shown to be associated with HBsAg loss over time. However, little is known about their impacts on HBsAg loss in HBeAg-negative patients with limited viral replication. A total of 688 HBeAg-negative patients with baseline serum HBV DNA levels <2000 IU/mL were enrolled in Taiwan. The relationships of HBsAg and HBV DNA levels with subsequent HBsAg loss were investigated. In a mean follow-up of 11.6 years, the average annual rate of HBsAg loss was 1.6%. Baseline HBsAg and HBV DNA levels were inversely associated with subsequent HBsAg loss. When compared to patients who had HBsAg levels >1000 IU/mL, the rates of HBsAg loss were significantly higher in patients with HBsAg levels of 100-999, 10-99, and <10 IU/mL, with hazard ratios of 2.5 (95% confidence interval [CI], 1.6-4.0), 2.8 (95% CI, 1.6-5.0), and 13.2 (95% CI, 8.1-21.5), respectively. Multivariate analysis showed that HBsAg level, but not HBV DNA, remained as an independent factor. The adjusted hazard ratio of HBsAg loss was 13.2 (95% CI, 7.8-22.1) for HBsAg level <10 versus ≥1000 IU/mL. When compared to HBV DNA level by receiver operating characteristic curve analysis, HBsAg level served as a better predictor of both 5-year and 10-year HBsAg loss. Conclusion: In HBeAg-negative patients with HBV genotype B or C infection who have HBV DNA level <2000 IU/mL, HBsAg level <10 IU/mL is the strongest predictor of HBsAg loss. (HEPATOLOGY 2012;55:68–76)

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