HBV RNA, HBcrAg, and HBsAg levels at year 6 do not predict HCC risk in patients with cirrhosis on long-term entecavir therapy.

Authors

Hung-Hsuan Pan, Tung-Hung Su, Tsung-Hui Hu, Wan-Long Chuang, Wei-Wen Su, Chun-Che Lin, Cheng-Yuan Peng, Chia-Chi Wang, Yao-Chun Hsu, Yi-Wen Huang, Kuo-Chih Tseng, Chih-Lin Lin, Sheng-Shun Yang, Fat-Moon Suk, Shih-Jer Hsu, Tsung-Ming Chen, Ming-Jong Bair, Cheng-Kuan Lin, Tai-Chung Tseng, Jia-Horng Kao, C-TEAM study group and the Taiwan Liver Diseases Consortium

Published in

Hepatology international. Aug 08, 2026. Epub Aug 08, 2026.

Abstract

The prognostic value of on-treatment hepatitis B virus (HBV) RNA, hepatitis B core-related antigen (HBcrAg), and quantitative hepatitis B surface antigen (HBsAg) for hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B (CHB) remains uncertain. We evaluate the predictive roles of these viral markers in patients with CHB receiving long-term entecavir therapy.
This prospective, multicenter study enrolled patients with CHB-related cirrhosis undergoing long-term entecavir treatment and HCC surveillance in Taiwan. Serum HBV RNA, HBcrAg, and HBsAg levels were measured at enrollment. Multivariable regression identified predictors of HBV RNA positivity and HCC development.
Overall, 451 patients were included. After a median of 6.2 years of antiviral therapy, the median levels of HBV RNA, HBcrAg, and HBsAg were 0.9 log10 copies/mL, 3.2 log10 U/mL, and 2.4 log10 IU/mL, respectively. During a median 3.3-year follow-up, 55 developed HCC. 57.2% of patients had detectable HBV RNA. HBV RNA detectability was associated with older age, lower alanine aminotransferase (ALT), HBeAg positivity, and higher HBsAg and HBcrAg levels. In multivariable analysis, higher fibrosis-4 (FIB-4) index (adjusted subdistribution hazard ratio [aSHR], 1.10; 95% confidence interval [CI] 1.00-1.21) and elevated alpha-fetoprotein (AFP) (aSHR, 1.01; 95% CI 1.00-1.01) independently predicted HCC development, whereas the three viral markers did not.
After a 6-year entecavir therapy, 57.2% of patients with CHB-related cirrhosis had detectable HBV RNA. Year-6 HBV RNA, HBcrAg, and HBsAg levels were not predictive of HCC, while FIB-4 index and AFP remained independent predictors.

PMID:
42570979
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.

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