Abstract: Objective The aim of this study was to investigate the clinical implication of serum HBV covalently closed circular DNA (HBV cccDNA) and HBV pregenomic RNA (HBV pgRNA) in patients with chronic hepatitis B (HBV) undergoing entecavir therapy. Methods A total of 89 patients with serum HBeAg-positive CHB were admitted to our hospital between January 2018 and January 2020, and all received entecavir therapy for 48 weeks. Serum HBV cccDNA, HBV pgRNA and HBV DNA loads were detected by fluorescent quantitative PCR under COOBAS TAQMAN and COBAS Amliprep systems. Serum HBsAg and HBeAg levels were detected by chemiluminescence method. The predicting performance of each parameter was analyzed by receiver operating characteristic (ROC) curve. Results At the end of 48 week observation, the virologic response was obtained in 85 cases(95.5%), biochemical response was obtained in 80 cases (89.9%), and serologic response in 9 cases (10.1%); the complete response (CR) as defined by both virologic and biochemical responses was gained in 75 cases(84.3%); at presentation, serum ALT, HBsAg, HBeAg, HBV DNA, HBV cccDNA and HBV pgRNA levels in patients with CR were (228.3±34.9)U/L, (2.5±0.4)lg IU/mL, (18.6±1.9)S/CO, (6.1±0.6)lg IU/mL, (2.2±0.2)cps/mL and (4.5±0.6)cps/mL, significantly different compared to [(69.5±17.1)U/L, (3.7±0.7)lg IU/mL, (163.2±16.3)S/CO,(6.8±0.7)lg IU/mL, (3.9±0.4)cps/mL and (7.0±0.7)cps/mL, respectively, P<0.05]; the area under ROC of serum HBV cccDNA and HBV pgRNA combination in predicting CR in patients with CHB receiving entecavir treatment was 0.892, with the sensitivity of 81.6% and specificity of 89.5%. Conclusion The combined detection of serum HBV cccDNA and HBV pgRNA is of high predictive value in patients with HBeAg-positive CHB before antiviral therapy, which needs further clinical investigation.

Key words: Hepatitis B, Entecavir, HBeAg positive, HBV cccDNA, HBV pgRNA, Therapy