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J Viral Hepat. 2019 Aug 16. doi: 10.1111/jvh.13191. [Epub ahead of print]

Hepatitis B core-related antigen levels after HBeAg seroconversion is associated with the development of hepatocellular carcinoma.

To WP1, Mak LY1, Wong DK1,2, Fung J1,2, Liu F1, Seto WK1,2,3, Lai CL1,2, Yuen MF1,2.

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Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.


Hepatitis B core-related antigen (HBcrAg) is a novel serological marker for hepatitis B virus infection. Its clinical significance after HBeAg seroconversion has not been defined. We aimed to determine the relationship between HBcrAg levels after spontaneous HBeAg seroconversion and hepatocellular carcinoma (HCC). A total of 207 chronic hepatitis B patients with documented time of HBeAg seroconversion were enrolled. HBcrAg and HBsAg were checked within 3 years (as baseline), at 5 and 10 years after HBeAg seroconversion. HBV DNA was measured at the baseline. Multivariate Cox regression model was used to investigate the predictors for HCC development. The median follow-up time was 13.1 (11.8-15.5) years. Fourteen patients developed HCC (15-year cumulative incidence: 7%). The median level of HBcrAg at baseline was significantly higher in patients who developed HCC when compared with patients without HCC (5.68 vs 4.78 log U/ml, respectively; P = .003). Cox proportional hazards model indicated that age of HBeAg seroconversion older than 40 years (hazard ratio (HR): 4.60; P = .049), presence of baseline cirrhosis (HR: 6.23; P = .003) and a higher baseline HBcrAg (HR: 1.75; P = .032) were independently associated with HCC development. A cut-off value of baseline HBcrAg level ≥5.21 log U/mL yielded an AUROC of 0.74 with a negative predictive value of 97.7%. High HBcrAg levels within 3 years after HBeAg seroconversion were independently associated with the development of HCC in chronic hepatitis B patients.


chronic hepatitis B; cirrhosis; hepatitis B core-related antigen; hepatocellular carcinoma


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