Predictive significance of serum pgRNA in HBeAg clearance for chronic hepatitis B patients with low HBeAg level after pegylated interferon treatment

Objective To evaluate the predictive efficacy of serum pregenomic RNA (pgRNA) level in HBeAg clearance for chronic hepatitis B (CHB) patients treated with polyethylene glycol interferon alfa (PEG-IFN-α). Methods Twenty-five CHB patients with HBeAg positive and quantitative < 50 S/CO treated in our outpatient department from November 2015 to July 2019 were recruited in this prospective study. They were treated with PEG-IFN-α alone or combined with nucleoside and nucleotide analogs (NAs) for 48 to 96 weeks. After treatment, the patients were followed up in the clinic. According to whether HBeAg was cleared during treatment or follow-up, the patients were divided into HBeAg clearance group (HBeAg quantitative < 1.00 COI) and HBeAg non-clearance group (HBeAg ≥1.00 COI). The baseline characteristics and dynamic changes of virological indexes were analyzed for every patient during treatment. The predictive value of virological markers to HBeAg clearance was evaluated by binary logistic regression analysis and receiver operating characteristic (ROC) curve. Results At the end of treatment, 13 patients (13/25, 52.00%) achieved HBeAg clearance. There were significant differences in the levels of serum pgRNA and HBcrAg between the 2 groups at baseline (P < 0.05); Baseline pgRNA was significantly correlated with HBcrAg (r=0.575, P=0.003) and HBeAg (r=0.496, P=0.012), and baseline HBcrAg was significantly correlated with HBeAg (r=0.888, P < 0.001) and HBsAg (r=0.423, P=0.035). During the treatment, the overall level of HBeAg in 25 patients showed a downward trend when compared with the baseline level, and the decline of HBeAg level was greater in the HBeAg clearance group than the HBeAg non-clearance group at different time points (P < 0.05). From baseline to 12 weeks, the levels of pgRNA and HBsAg were decreased significantly, and its decline of pgRNA was more significant in the HBeAg clearance group than the non-clearance group (P < 0.05). During the whole treatment process, the level of HBcrAg was in a slow downward trend, and a significant decrease was observed only at 12 to 24 week in the HBeAg clearance group (P < 0.05), not at other time points. ROC curve analysis showed that baseline pgRNA and HBcrAg were good indicators to predict HBeAg clearance. Multivariate binary logistic regression analysis indicated that baseline pgRNA level was an independent predictor of HBeAg clearance after treatment (P < 0.05), with an AUC of 0.763, cutoff value of 2.42 log10 copies/mL, a sensitivity of 69.23% and a specificity of 53.85%. Conclusion Pretreatment serum level of pgRNA shows good predictive value for the efficacy of PEG-IFN-α in CHB patients with low HBeAg level.