Serum hepatitis B core-related antigen predicts hepatocellular carcinoma in hepatitis B e antigen-negative patients

Abstract

Background

Hepatitis B core-related antigen (HBcrAg) is a novel serum viral marker. Recent studies showed that its level correlates with the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to evaluate the accuracy of serum HBsAg and HBcrAg levels at baseline to predict HCC.

Methods

1400 CHB patients who received nucleos(t)ide analogues (NA) treatment since December 2005 were included. Their stored serum samples at baseline were retrieved to measure HBsAg and HBcrAg levels. The primary endpoint was the cumulative incidence of HCC.

Results

85 (6.1%) patients developed HCC during a mean (± SD) follow-up duration of 45 ± 20 months. Serum HBcrAg level above 2.9 log10 U/mL at baseline was an independent factor for HCC in hepatitis B e antigen (HBeAg)-negative patients by multivariable analysis (adjusted hazard ratio 2.13, 95% CI 1.10–4.14, P = 0.025). HBcrAg above 2.9 log10 U/mL stratified the risk of HCC in HBeAg-negative patients with high PAGE-B score (P = 0.024 by Kaplan–Meier analysis), and possibly in cirrhotic patients (P = 0.08). Serum HBsAg level did not show any correlation with the risk of HCC in all patients or any subgroups.

Conclusion

Serum HBcrAg level predicts the risk of HCC accurately in NA-treated HBeAg-negative CHB patients.

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Acknowledgement

This work was supported by the Health and Medical Research Fund (HMRF) of the Food and Health Bureau (Reference no: 15160551) award to Grace Wong.

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Affiliations

Authors

Contributions

All authors were responsible for the study concept and design. Lilian Liang, Yee-Kit Tse, Terry Yip, Becky Yuen and Grace Wong were responsible for the acquisition and analysis of data, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors were responsible for the interpretation of data, the drafting, and critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Grace Lai-Hung Wong.

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Conflict of interest

Vincent Wong has served as an advisory committee member for 3 V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Janssen, Novartis, Novo Nordisk, Perspectum Diagnostics, Pfizer, TARGET-NASH and Terns; and a speaker for Bristol-Myers Squibb, Echosens, Gilead Sciences and Merck. He has also received a research grant from Gilead Sciences. Hidenori Toyoda has served as a speaker for AbbVie and Merck. Terry Yip has served as a speaker for Gilead Sciences. Takashi Kumada has served as a speaker for Abbvie, Eisai and Gilead Sciences. Henry Chan is an advisor for AbbVie, Aptorum, Altimmune, Arbutus, Intellia, Janssen, Gilead, GRAIL, Medimmune, Roche, Vir Biotechnology; and a speaker for AbbVie, Gilead and Roche. Grace Lui has served as an advisory committee member for Gilead, speaker for Merck and Gilead, and received research grant from Gilead. Grace Wong has served as an advisory committee member for Gilead Sciences, as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Furui, Gilead Sciences, Janssen and Roche, and received research grant from Gilead Sciences. The other authors declare that they have no conflict of interest (potential personal and financial interests inclusive).

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Liang, L.Y., Wong, V.W., Toyoda, H. et al. Serum hepatitis B core-related antigen predicts hepatocellular carcinoma in hepatitis B e antigen-negative patients. J Gastroenterol (2020). https://doi.org/10.1007/s00535-020-01700-z

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Keywords

  • Hepatitis B core-related antigen
  • Hepatitis B surface antigen
  • Hepatocellular carcinoma
  • Antiviral agents