Serum HBcrAg and Hepatocellular Carcinoma in a Taiwanese Population Seronegative for HBsAg and Anti-HCV

Yi Chung Hsieh, Mei Hung Pan, Wen Juei Jeng*, Hui Han Hu, Jessica Liu, Masashi Mizokami, Chien Jen Chen, Hwai I. Yang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations


BACKGROUND & AIMS: Hepatitis B core-related antigen (HBcrAg) is a surrogate seromarker of intrahepatic hepatitis B virus covalently closed circular DNA quantity and activity and a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B patients. We assess association between HBcrAg and HCC in individuals seronegative for hepatitis B surface antigen and anti-hepatitis C virus (NBNC) in Taiwan.

METHODS: A total of 129 newly developed HCC cases and 520 frequency-matched non-HCC controls were drawn from the REVEAL-NBNC cohort. Serum HBcrAg and other risk factors measured at recruitment were compared between cases and controls. Regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: The proportion of baseline HBcrAg positivity (≥1000 U/mL) was significantly higher in HCC cases than in controls (12.4% vs 1.4%, P < .001). In multivariate analysis, HBcrAg positivity was associated with significantly higher risk of HCC (adjusted OR [95% CI]: 9.3 [3.3-26.4]; P < .001]. The HCC population attributable to HBcrAg positivity was 11.1% (95% CI: 9.7%-12.5%).

CONCLUSIONS: Seropositivity of HBcrAg might identify a subset of the NBNC population at higher risk of HCC in hepatitis B virus endemic areas.

Original languageEnglish
Pages (from-to)1303-1313.e11
JournalClinical Gastroenterology and Hepatology
Issue number5
StatePublished - 05 2023

Bibliographical note

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.


  • Non-Hepatitis B
  • Non-Hepatitis C
  • Nonalcoholic Fatty Liver Disease
  • Occult HBV
  • Hepatitis B, Chronic
  • Humans
  • Liver Neoplasms/epidemiology
  • Hepatitis B Surface Antigens
  • Hepatitis B Core Antigens
  • DNA, Circular
  • Biomarkers
  • Carcinoma, Hepatocellular/epidemiology
  • DNA, Viral
  • Hepatitis B virus/genetics


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