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The role of quantitative hepatitis B surface antigen revisited

  • Markus Cornberg
    Affiliations
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany
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  • Vincent Wai-Sun Wong
    Affiliations
    Department of Medicine and Therapeutics, Institute of Digestive Disease and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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  • Stephen Locarnini
    Affiliations
    Victorian Infectious Diseases Reference Laboratory (VIDRL), Doherty Institute for Infection and Immunity, Melbourne, Australia
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  • Maurizia Brunetto
    Affiliations
    Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Italy
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  • Harry L.A. Janssen
    Affiliations
    Toronto Center for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
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  • Henry Lik-Yuen Chan
    Correspondence
    Corresponding author. Address: Department of Medicine and Therapeutics, 9/F Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong. Tel.: +852 26321056.
    Affiliations
    Department of Medicine and Therapeutics, Institute of Digestive Disease and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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Published:August 27, 2016DOI:https://doi.org/10.1016/j.jhep.2016.08.009

      Summary

      In the past 10 years, there has been a lot of enthusiasm surrounding the use of serum hepatitis B surface antigen (HBsAg) quantification to predict disease activity and monitor treatment response in chronic hepatitis B. The measurement of HBsAg levels have been standardized in IU/ml, and nowadays it is almost a mandatory measurement due to the development of new antiviral treatments aiming at HBsAg seroclearance, i.e., functional cure of hepatitis B. Recently, there has been an improved understanding of the molecular virology of HBsAg, and particularly the relative roles of covalently closed circular DNA and integrated hepatitis B virus (HBV) DNA. This has shed new light on the interpretation of HBsAg levels in different phases of chronic hepatitis B. HBsAg level can assist the differentiation of immune tolerance and immune clearance in hepatitis B e antigen (HBeAg)-positive patients, and it can predict inactive disease and spontaneous HBsAg seroclearance in HBeAg-negative patients. The determination of HBsAg level is pivotal to individualize pegylated interferon (PegIFN) treatment; it is the key investigation to decide early termination of PegIFN among non-responders. Among patients treated by nucleos(t)ide analogues, responders tend to have dramatic reduction of HBsAg to low levels, which may be followed by HBsAg seroclearance. With newer data on combination treatment of PegIFN and nucleos(t)ide analogues as well as emerging new antiviral agents, HBsAg quantification is expected to become increasingly important to monitor and guide antiviral therapy for chronic hepatitis B.

      Keywords

      Linked Article

      • Reply to: “Serum HBsAg kinetics in clinical prediction”
        Journal of HepatologyVol. 67Issue 1
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          We agree with W-J Jeng and Y-F Liaw on the pivotal role of spontaneous hepatitis B surface antigen (HBsAg) serum clearance in the clinical history of a hepatitis B virus (HBV) carrier [1] as it is, the hallmark of the control of HBV replication and transition from inactive to occult infection [2]. However, the reported annual rates of HBsAg clearance are highly variable (0.31 to 3.2 × 100 persons/years) because of the heterogeneity of the studied populations [3–6]: mode of infection, age and ethnicity are major factors influencing the HBsAg loss [5–8].          
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      • Serum HBsAg kinetics in clinical prediction
        Journal of HepatologyVol. 67Issue 1
        • Preview
          We read with great interest the review article “The role of quantitative hepatitis B surface antigen revisited” by Cornberg et al. in the Journal of Hepatology [1]. Indeed, it is a comprehensive update. However, the role of hepatitis B surface antigen (HBsAg) quantification in the prediction of spontaneous or antiviral therapy related HBsAg seroclearance and relapse after cessation of nucleos(t)ide analog (NUC) therapy was not well addressed. The studies mentioned in the review used an HBsAg level <100 IU/ml as a predictor for remote (6–10 years) HBsAg seroclearance but two studies on short-term prediction of HBsAg seroclearance within 1–3 years were not mentioned.              
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