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Use of HBsAg quantification in the natural history and treatment of chronic hepatitis B

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Abstract

In patients with chronic hepatitis B (CHB) infection, it is important to monitor the natural history, assess treatment response, and predict the risk of liver-related complications. Quantification of serum hepatitis B surface antigen (HBsAg) has gained wide interests since the last decade. It is secreted from hepatocytes in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases of the disease, and can be transcribed and translated from different sources of viral genome [ccc DNA or integrated hepatitis B virus (HBV) DNA]. In untreated patients, it declines slowly through the natural course and remains stable for a long time after HBeAg seroconversion. In patients treated with nucleos(t)ide analogues (NA), it also declines very slowly, even though serum hepatitis B DNA has been rendered negative. Low serum HBsAg may predict either spontaneous or treatment-induced HBsAg seroclearance, and potentially selects out HBeAg-negative patients who can safely stop NA. High serum HBsAg is associated with high risk of hepatocellular carcinoma in untreated population, and predicts treatment failure in patients receiving pegylated interferon. These potential roles of HBsAg quantification are applicable to selected populations only. There is also a need for novel markers to study the effect of emerging antiviral therapies targeting various parts of the HBV cycle to reflect their distinct mechanistic effects. Several agents measuring HBsAg levels have shown rapid and significant decline. Ongoing studies are required to demonstrate the sustainability of HBsAg suppression by these novel agents.

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  1. Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road 102, Hong Kong, China

    Lung-Yi Mak, Wai-Kay Seto, James Fung & Man-Fung Yuen

  2. State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China

    Wai-Kay Seto, James Fung & Man-Fung Yuen

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WKS received speaker fees from Mylan; received speaker fees and is an advisory board member of AbbVie; and received speaker fees, is an advisory board member and received research funding from Gilead Sciences.; MFY serves as advisor/consultant for AbbVie, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals and receives Grant/research supports from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, and Sysmex Corporation. J. Fung and L. Y. Mak have no potential conflict of interest to disclose.

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Mak, LY., Seto, WK., Fung, J. et al. Use of HBsAg quantification in the natural history and treatment of chronic hepatitis B. Hepatol Int 14, 35–46 (2020). https://doi.org/10.1007/s12072-019-09998-5

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