The role of hepatitis B virus core‐related antigen in predicting hepatitis B virus relapse after cessation of entecavir in hepatitis B e antigen‐negative patients

Abstract This study investigated the ability of hepatitis B core‐related antigen (HBcrAg) to predict hepatitis B virus (HBV) relapse in HBeAg‐negative patients after cessation of entecavir therapy. A total of 301 HBeAg‐negative patients without cirrhosis who had stopped entecavir therapy for at least 12 months were recruited. All patients fulfilled the stopping criteria proposed by the APASL 2012 guidelines. The five‐year cumulative rates of virological relapse, clinical relapse and HBsAg loss were 71.6%, 57.3% and 18.7%, respectively. Serum HBsAg at end of treatment (EOT) was an independent predictor of virological relapse, clinical relapse and HBsAg loss; an EOT HBsAg of 150 IU/ml was the optimal cut‐off value. The 5‐year virological relapse rates for patients with <150 and ≥150 IU/ml HBsAg at EOT were 43.3% and 82.2% ( p < 0.001), clinical relapse rates were 32.3% and 66.3% ( p < 0.001), and HBsAg loss rates were 46.1% and 5.2% ( p < 0.001), respectively. A baseline HBcrAg of 4 IU/ml was the optimal cut‐off value for predicting HBV relapse. Among patients with an EOT HBsAg <150 IU/ml, the five‐year virological relapse rates for patients with baseline HBcrAg levels ≤4 and >4 log U/ml were 27.9% and 59.1% ( p = 0.006) and the clinical relapse rates were 18% and 48.1% ( p = 0.014), respectively. EOT HBcrAg was not a significant predictor of virological or clinical relapse after cessation of entecavir. In conclusion, the combination of an EOT HBsAg of 150 IU/ml and baseline HBcrAg of 4 log U/ml can effectively predict the risk of HBV relapse after stopping entecavir therapy.