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

Summary: Background: 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. Aim: 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. Methods: This retrospective cohort study included 1268 patients treated with NAs for >1 year. In all patients, serum HBcrAg and hepatitis B surface antigen levels were measured at baseline and 1 year. Results: During a median follow‐up of 8.9 years, 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 1 year 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. Conclusions: Patients with persistently high on‐treatment HBcrAg levels were more likely to develop HCC despite sustained viral suppression via long‐term NA treatment. [ABSTRACT FROM AUTHOR]