Hepatitis B virus core-related antigen levels predict progression to liver cirrhosis in hepatitis B carriers

Abstract

Background and aim: Several hepatitis B virus (HBV) markers have been identified as risk factors for progression to liver cirrhosis in patients with chronic HBV infection. The predictive impact of HBV markers on progression to cirrhosis in HBV carriers was clarified.

Methods: A total of 529 hepatitis B e antigen seroconverters with fibrosis-4 (FIB-4) index ≤ 3.6 not on nucleos(t)ide analogue therapy were included. Univariate and multivariate analyses of associations between HBV markers and progression to cirrhosis were performed. In addition, the hazard ratio (HR) spline curves for continuous HBV markers were compared.

Results: Eighty-four patients progressed to cirrhosis (FIB-4 index > 3.6) during the follow-up period. Hepatitis B surface antigen (HBsAg), HBV DNA, HBV core-related antigen (HBcrAg), and basal core promoter status, but not genotype and precore status, were significantly associated with progression to cirrhosis in univariate Cox proportional hazards models. Multivariate Cox proportional hazards models adjusted for HBV genotype, HBsAg, HBV DNA, HBcrAg, precore status, and basal core promoter status indicated that HBsAg ≥ 3.0 log IU/mL (HR, 0.53; 95% confidence interval [CI], 0.30-0.94) and HBcrAg ≥ 3.7 log U/mL (HR, 3.28; 95% CI, 1.60-6.75) are independently associated with progression to cirrhosis. In the HR spline curve analysis, HR and 95% CI gradually increased as HBcrAg levels increased. Conversely, HRs and 95% CIs for HBsAg and HBV DNA did not show this tendency as their levels increased.

Conclusions: Elevated HBcrAg levels in HBV carriers increases the risk for progression to cirrhosis. HBcrAg is an excellent predictor of the development of cirrhosis.

Keywords: Fibrosis-4 index; hepatitis B; hepatitis B virus core-related antigen; liver cirrhosis.