Abstract: Objective The aim of this study was to explore the predictive value of antiviral response by serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) levels in naïve patients with hepatitis B receiving nucleos(t)ide analogues treatment. Methods 107 naïve patients with chronic hepatitis B (CHB) were enrolled in our hospital between August 2015 and December 2019, and all were treated with nucleos(t)ide analogues, e.g. entecarvir, tenofovir, or telbivodine, for 12 months. Serum HBV pgRNA loads was assayed by real-time fluorescent quantitative PCR, serum HBsAg and HBeAg were detected by ELISA, the multivariate Logistic regression model was applied to analyze the influencing factors of response in CHB patients to nucleos(t)ide analogue treatment, and the area under the receiver operating characteristic curve (AUROC) was applied to predict the antiviral response by serum HBV pgRNA levels in CHB patients receiving nucleos(t)ide analogue treatment. Results At the end of 48 week observation, 27 patients (25.2%) didn't response to antiviral therapy, but 80 patients(74.8%) obtained complete or partial response; serum HBV DNA loads in patients with CR and PR was (6.1±1.0)lg copies/mL, significantly lower than [(7.2±1.2) lg copies/mL, P<0.05], peripheral blood 血CD4^＋/CD8^＋ cell ratio was (0.7±0.2), significantly higher than [(0.6±0.1), P<0.05], serum HBeAg positive rate was 41.3%, significantly lower than (70.4%, P<0.05),and serum HBV pgRNA level was (5.3±0.8)lg copies/mL, significantly lower than [(6.5±1.1)lg copies/mL, P<0.05] in non-responders; the multivariate Logistic regression analysis showed that baseline serum HBV DNA loads, serum HBeAg state and serum HBV pgRNA levels were the independent influencing factors for antiviral response in CHB patients receiving nucleos(t)ide analogue treatment(OR=2.793, OR=3.827, OR=4.035, all P<0.05); the ROC analysis demonstrated that the optimal cut-off-value of serum HBV pgRNA level in predicting response of antiviral therapy in CHB patients was 5.89 lg copies/mL, with the AUC of 0.865(95%CI:0.816-0.905), the sensitivity of 74.1%(20/27) and the specificity of 88.8%(71/80). Conclusion Serum HBV pgRNA levels could be assayed in sera of patients with CHB, and it might be used to predict the antiviral response and warrants further clinical investigation.

Key words: Hepatitis B, Hepatitis B virus pregenomic RNA, Nucleos(t)ide analogues, Response, Prediction