Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon‐based therapy in patients with hepatitis B e antigen‐negative chronic hepatitis B

Abstract Serum hepatitis B virus (HBV) RNA has emerged as a novel biomarker of treatment response. This study aimed to investigate the role of this marker in predicting long‐term outcome of patients with hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (CHB) receiving pegylated interferon (PEG‐IFN)‐based therapy. Serial serum samples from 91 patients with HBeAg‐negative CHB previously treated with PEG‐IFN alone or combined with entecavir in a randomized trial were retrospectively analysed. HBV RNA quantification was examined by droplet digital PCR. At the end of 3 years post‐treatment follow‐up, maintained virological response (MVR, HBV DNA < 2000 IU/mL), and hepatitis B surface antigen (HBsAg) clearance were achieved in 37.4% (34/91) and 7.7% (7/91), respectively. Baseline serum HBV RNA concentrations correlated with HBV DNA and covalently closed circular DNA but did not correlate with HBsAg levels. Multiple regression analysis showed that pre‐treatment HBV RNA and HBsAg were independently associated with MVR and HBsAg clearance. Baseline HBV RNA (cut‐off 2.0 log 10 copies/mL) had a positive predictive value (PPV) and a negative predictive value in predicting MVR of 80.8% and 80.0%, respectively. At the same cut‐off value, PPV and NPV for predicting HBsAg clearance were 30.8% and 95.4%, respectively. At week 12 during therapy, HBV RNA level ≥ 2 log 10 copies/mL displayed high NPVs of achieving MVR and HBsAg clearance (95% and 100%, respectively). In conclusion, the measurement of HBV RNA prior to PEG‐IFN‐based therapy could identify patients with high probability of MVR. In addition, HBV RNA kinetics may serve as a promising “stopping rule” in patients infected with HBV genotypes B or C.