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Clinical utility of HBV surface antigen quantification in HBV e antigen-negative chronic HBV infection

Nature Reviews Gastroenterology & Hepatology volume 16, pages 631–641 (2019)Cite this article

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Abstract

Chronic hepatitis B virus (HBV) infection is a serious problem owing to its worldwide distribution and potential adverse sequelae that include cirrhosis and/or hepatocellular carcinoma. Current antiviral therapies have much improved outcomes, but few patients achieve the ultimate goal of hepatitis B surface antigen (HBsAg) loss (functional cure). As hepatitis B e antigen (HBeAg)-negative chronic HBV infection is the final phase prior to HBsAg loss, the management of patients in this phase together with quantification of HBsAg has attracted increasing clinical and research interest. This Review integrates the findings from research in HBsAg kinetics and discusses how they might inform our understanding and management of HBeAg-negative chronic HBV infection. Studies have shown that HBsAg levels are highly predictive of the presence of inactive HBV infection and that serial changes in HBsAg levels might predict HBsAg loss within 1–3 years. Data also suggest that quantitative HBsAg monitoring is important during hepatitis flare and antiviral therapy, especially in the timing of the decision to stop therapy and to start off-therapy retreatment. These findings have shed new light on the natural course of HBV infection and might lead to optimization of the management of HBeAg-negative chronic HBV infection and contribute to the paradigm shift from indefinite to finite therapy for patients with HBV infection.

Key points

  • Chronic hepatitis B virus (HBV) infection is a serious clinical problem involving ~292 million people worldwide, and has the potential risk of adverse sequelae including cirrhosis and hepatocellular carcinoma.

  • A hepatitis B surface antigen (HBsAg) level <1,000 IU/ml is indicative of inactive infection and a level <200 IU/ml with decline of >0.5 log10 IU/ml per year predicts HBsAg loss within 1–3 years.

  • A hepatitis B e antigen (HBeAg)-negative patient with active infection requires nucleoside or nucleotide analogue (NUC) or interferon-based therapy; interferon-based therapy increases HBsAg decline and rate of loss.

  • Rapid HBsAg decline of >0.5 log10 IU/ml in 6 months can lead to HBsAg levels of <100 IU/ml or HBsAg loss during NUC therapy.

  • Stopping NUC therapy in sustained responders and those who achieve HBsAg <100 IU/ml by the end of therapy might increase the 5-year HBsAg loss by up to >30%.

  • HBsAg kinetics during clinical relapse can help the retreatment decision; retreatment is required in those with increasing HBsAg levels, whereas retreatment might be unnecessary in those with decreasing HBsAg levels.

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Fig. 1: Natural course of chronic HBV infection.
Fig. 2: Schematic diagram of the HBV life cycle and its immunopathogenesis.
Fig. 3: HBsAg kinetics in inactive HBeAg-negative chronic HBV infection.
Fig. 4: HBsAg kinetics during hepatitis B flares with different outcomes.
Fig. 5: Flow chart of suggested quantitative HBsAg assay timings.

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Acknowledgements

The author has been supported by grants from Chang Gung Medical Research Fund (CMRPG1G0061-3) and the Prosperous Foundation, Taipei, Taiwan. The author thanks Su-Chiung Chu for assistance in preparing the manuscript and figures.

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Nature Reviews Gastroenterology & Hepatology thanks N. Coppola, P. Marcellin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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  1. Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

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Liaw, YF. Clinical utility of HBV surface antigen quantification in HBV e antigen-negative chronic HBV infection. Nat Rev Gastroenterol Hepatol 16, 631–641 (2019). https://doi.org/10.1038/s41575-019-0197-8

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