Abstract: Objective This study was aimed to investigate serum HBsAg clearance and its influencing factors in patients with chronic hepatitis B (CHB) undergoing pegylated interferon α-2b (Peg-IFNα-2b) and nucleos(t)ide analogue (NAs) combination treatment. Methods A total of 246 patients with CHB, including naÏve in 119 cases and previously NAs-treated in 127 cases, were enrolled in our hospital between January 2018 and August 2024, and all received Peg-IFNα-2b in combination with NAs therapy for 48 weeks. Binary Logistic regression analysis was applied to identify factors impacting serum HBsAg clearance, and receiver operating characteristic curve (ROC) with the area under the curve (AUC) was drawn to evaluate predicting efficacy. Results By end of 48 week treatment, serum HBsAg clearance was obtained in 55 cases (22.4%) in our series; serum HBsAg clearance rate in NAs-treated patients was 70.9%,much higher than 29.1%(P＜0.05) in naive patients; baseline serum HBsAg level and HBV DNA load in HBsAg clearance group were (2.6±0.6)lg IU/mL and (2.1±1.0)lg IU/mL,both much lower than[(3.3±0.7)lg IU/mL and (2.7±1.4)lg IU/mL,respectively, P＜0.05] in those without HBsAg clearance; by end of 24 week antiviral treatment, incidence of decreased serum HBsAg level(＞1 lg IU/mL)in those with HBsAg clearance was 81.8%,much higher than 17.8%(P＜0.05)in those without serum HBsAg clearance; multivariate Logistic regression analysis showed that baseline serum HBsAg level, decreased serum HBsAg at 24 week antiviral treatment and NAs-treated were all the independent impacting factors for serum HBsAg clearance (P＜0.05);ROC analysis demonstrated that the AUC was 0.748,with sensitivity of 73.3% and specificity of 78.2%, when baseline serum HBsAg＜537.77 IU/mL was set as the cut-off-value in predicting serum HBsAg clearance. Conclusion The optimal alleged patients with CHB might be those with low serum HBsAg levels and low serum HBV DNA loads with long-term NAs treatment for Peg-IFNα-2b and NAs combination antiviral treatment, who will obtain functional cure.

Key words: Hepatitis B, Pegylated interferon α-2b, Nucleos(t)ide analogues, HBsAg clearance, Functional cure