Kinetics of serum HBsAg and intrahepatic cccDNA during pegylated interferon therapy in patients with HBeAg‐positive and HBeAg‐negative chronic hepatitis B

This study was aimed at comparing clinical applicability of serum HBsAg quantification in relation to intrahepatic covalently closed‐circular DNA (cccDNA) in patients with HBeAg‐positive and HBeAg‐negative chronic hepatitis B (CHB) treated with pegylated interferon (PEG‐IFN) monotherapy for 48 weeks. Overall, 32 and 36 patients with HBeAg‐positive and HBeAg‐negative CHB, respectively were recruited. Paired liver biopsies at baseline and end of therapy were analyzed for cccDNA. Virological response (VR) at 48 weeks post‐treatment was defined as HBeAg clearance (for HBeAg‐positive CHB) and HBV DNA <2,000 IU/ml (for both groups). The results demonstrated that baseline levels of all viral markers were higher in the HBeAg‐positive group than the HBeAg‐negative group. Baseline HBsAg correlated with cccDNA in the HBeAg‐positive group (r = 0.452, P = 0.009) but not in the HBeAg‐negative group (r = 0.018, P = 0.919). However, the magnitude of cccDNA and HBsAg decline at end of treatment was not different between groups. The reduction of HBsAg showed a positive correlation with cccDNA decline in HBeAg‐positive and HBeAg‐negative CHB (r = 0.544, P = 0.001 and r = 0.364, P = 0.029, respectively). Overall, responders had more decline in cccDNA and HBsAg levels compared with non‐responders. Patients with serum HBsAg decline of >1.0 log10 IU/ml during treatment archived VR and HBsAg clearance of 80% and 30%, respectively. In conclusion, serum HBsAg represented a better surrogate marker of intrahepatic cccDNA in patients with HBeAg‐positive CHB compared to those with HBeAg‐negative CHB. On‐treatment, HBsAg reduction of 1.0 log10 IU/mL was associated with a high probability of subsequent VR and HBsAg clearance in patients receiving PEG‐IFN therapy. J. Med. Virol. 89:130–138, 2017. © 2016 Wiley Periodicals, Inc.