Predictive role of serum HBsAg and HBcrAg kinetics in patients with HBeAg-negative chronic hepatitis B receiving pegylated interferon–based therapy

Abstract Objectives To investigate the role of serum hepatitis B core-related antigen (HBcrAg) kinetics in predicting long-term outcome of pegylated interferon (PEG-IFN)-based therapy in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). Methods A total of 121 Thai patients with HBeAg-negative CHB recruited from a previous randomized trial of 48-week PEG-IFN alone or combined with entecavir were enrolled. Hepatitis B surface antigen (HBsAg) and HBcrAg levels were serially examined. Paired biopsy samples taken at baseline and after treatment were assessed for intrahepatic covalently closed circular DNA (cccDNA). Results Persistent virologic remission (PVR, defined by persistent hepatitis B virus (HBV) DNA 10 IU/mL plus HBcrAg ≥3.7 log 10 U/mL) yielded high negative predictive values of PVR (45/50, 90%) and HBsAg clearance (50/50, 100%). At week 12, declines of HBsAg, HBcrAg and both antigens combined of 10 yielded negative predictive values for PVR of 90% (71/79), 82% (61/74) and 96% (48/50) respectively. Conclusions Quantitative HBcrAg was significantly associated with cccDNA in HBeAg-negative CHB. This novel antigen, together with HBsAg, could identify patients with low probability of PVR and HBsAg clearance in long-term follow-up.