High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy

Simon J Hume ^1,2,3, Danny K Wong ⁴, Man-Fung Yuen ⁴

¹St Vincent's Hospital Melbourne, Fitrozy, Victoria, Australia.
²Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
³Victorian Infectious Diseases Reference Laboratory, Department of Infectious Diseases, Royal Melbourne Hospital, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁴Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁵Western Health, Melbourne, Australia.
⁶Monash Health, Melbourne, Victoria, Australia.
⁷Liverpool Hospital, Sydney, New South Wales, Australia.
⁸Alfred Health, Melbourne, Victoria, Australia.
⁹Eastern Health, Melbourne, Victoria, Australia.
¹⁰Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
¹¹Concord Hospital, Sydney, New South Wales, Australia.
¹²Austin Health, Melbourne, Victoria, Australia.
¹³Bankstown-Lindcombe Hospital, Sydney, New South Wales, Australia.
¹⁴St Vincent's Hospital Sydney, Sydney, New South Wales, Australia.

⁰St Vincent's Hospital Melbourne, Fitrozy, Victoria, Australia.

Liver International : Official Journal of the International Association for the Study of the Liver +

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July 15, 2024

View abstract on PubMed

Summary

Serum hepatitis B core-related antigen (HBcrAg) levels predict outcomes after nucleos(t)ide analogue (NA) therapy discontinuation. High HBcrAg indicates a risk of hepatitis flare and a low chance of HBsAg loss, deeming patients unsuitable for stopping NA treatment.

Area Of Science

Hepatology
Virology
Biomarker Discovery

Background

Accurate biomarkers are needed to predict outcomes after nucleos(t)ide analogue (NA) therapy cessation in chronic hepatitis B patients.
Serum hepatitis B core-related antigen (HBcrAg) is a potential biomarker for predicting treatment outcomes.

Purpose Of The Study

To evaluate serum HBcrAg levels as a predictive biomarker for clinical outcomes following NA discontinuation.
To assess the utility of HBcrAg in identifying patients at risk for hepatitis flare and those unlikely to achieve HBsAg loss.

Main Methods

A prospective trial involving HBeAg-negative chronic hepatitis B patients without cirrhosis undergoing NA discontinuation.
Measurement of serum HBcrAg, HBsAg, HBV RNA, and HBV DNA at end of treatment (EOT) and off-treatment.
Prediction of key clinical outcomes including hepatitis flare, biochemical relapse, virological relapse, and HBsAg loss.

Main Results

HBcrAg was detectable in 86% of participants.
HBcrAg levels ≥4 log U/mL at EOT predicted hepatitis flare (80% vs. 31%, p=.001).
High HBcrAg or detectable HBV RNA at EOT predicted biochemical relapse and hepatitis flare. No participant with EOT HBcrAg ≥4 log U/mL achieved HBsAg loss.

Conclusions

High serum HBcrAg levels are associated with an increased risk of hepatitis flare after NA discontinuation.
Elevated HBcrAg levels indicate a low likelihood of achieving HBsAg loss within 96 weeks.
Patients with high HBcrAg levels are not suitable candidates for NA discontinuation due to the risk of adverse outcomes.

Keywords:

biomarker hepatitis B hepatitis B core‐related antigen hepatitis flare nucleot(s)ide analogue nucleot(s)ide analogue discontinuation