Impact of hepatitis B core-related antigen on the incidence of hepatocellular carcinoma in patients treated with nucleos(t)ide analogues.

Abstract

Chronic hepatitis B virus (HBV) infection is an aetiologic factor for hepatocellular carcinoma (HCC). Baseline HBV DNA is a known independent predictor of HCC, and the serum hepatitis B core-related antigen (HBcrAg) level corresponds to intrahepatic covalently closed circular DNA. To investigate whether the baseline and on-treatment serum HBcrAg levels can predict HCC incidence in patients with chronic hepatitis B following nucleos(t)ide analogue (NA) therapy. This retrospective cohort study included 1268 patients treated with NAs for >1year. In all patients, serum HBcrAg and hepatitis B surface antigen levels were measured at baseline and 1year. During a median follow-up of 8.9years, 113 patients (8.9%) developed HCC (10.3/1000 person-years). These patients were stratified by baseline hepatitis B e-antigen (HBeAg) status into HBeAg+ and HBeAg- cohorts. High on-treatment HBcrAg levels at 1year were found to associate significantly with HCC (HBeAg+ cohort: P=0.017; HBeAg- cohort: P=4.30×10-5 ; cut-off values: 4.9 log U/mL and 4.4 log U/mL, respectively). In a multivariate Cox regression analysis, patients with persistently high on-treatment HBcrAg levels had a higher risk of HCC than those with low HBcrAg levels (HBeAg+: hazard ratio [HR], 6.15, 95% confidence interval [CI]: 1.89-20.0, P=0.003; HBeAg- cohort: HR, 2.54, 95% CI: 1.40-4.60; P=0.002). A sub-analysis of patients without alcoholism yielded similar findings. Patients with persistently high on-treatment HBcrAg levels were more likely to develop HCC despite sustained viral suppression via long-term NA treatment.