Serum hepatitis B core‐related antigen as a treatment predictor of pegylated interferon in patients with HBeAg‐positive chronic hepatitis B

Abstract Background & Aims The role of quantitative serum hepatitis B core‐related antigen ( HB crAg) in patients with chronic hepatitis B ( CHB ) receiving pegylated interferon ( PEG ‐ IFN ) is unclear. This study was aimed at comparing its usefulness with quantitative HB sAg in patients with HB eAg‐positive CHB receiving PEG ‐ IFN therapy. Methods A total 46 patients treated with PEG ‐ IFN for 48 weeks were retrospectively analysed. Intrahepatic covalently closed circular DNA (ccc DNA ) from paired liver biopsies and serial serum HB sAg and HB crAg during therapy were assessed. Results Virological response ( VR ), defined as HB eAg clearance and HBV DNA <2000 IU /ml at 24 weeks post treatment, was achieved in 15 (32.6%) patients. Responders had significantly higher ccc DNA decline from baseline compared with non‐responders. Baseline HB sAg and HB crAg were correlated with ccc DNA ( r = 0.424, P = 0.020 and r = 0.564, P = 0.001, respectively), and changes in the corresponding markers during therapy were correlated with ccc DNA reduction ( r = 0.579, P = 0.001 and r = 0.503, P = 0.005, respectively). Responders showed more rapid decline of both markers during therapy compared with non‐responders. In multivariate analysis, serum HB crAg at week 12 was identified as a predictor of VR . The optimal cut‐off value for HB crAg (log 10 8.0 U/ml) provided negative predictive value ( NPV ) of achieving VR at weeks 12 and 24 of 94.4 and 100%, respectively, while using HB sAg > 20 000 IU /ml provided NPV of 80 and 100% respectively. Conclusions The convenient quantitative HB crAg represented a reliable marker of intrahepatic ccc DNA . Monitoring HB crAg levels during PEG ‐ IFN therapy may help identify patients with a very low probability of response comparable to, if not better than, quantitative HB sAg.