To evaluate the clinical efficacy and influencing factors of pegylated interferon (PegIFNα-2b) combined with nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB) patients with low level of hepatitis B virus surface antigen (HBsAg).

This study was a prospective, nonrandomized, controlled, real-world study, which selected patients who had been treated with NAs for more than one year in Jinling Hospital from January 2018 to May 2020 and achieved serum HBsAg ≤ 1 500 IU/ml and HBV DNA < 50 IU/ml, they were all treated with NAs and PegIFNα-2b. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), HBV serum markers, and HBV DNA quantification were collected from all patients at 0, 12th, 24th, 36th, and 48th week. Patients were divided into clinically cured group (13 cases) and non-cured group (32 cases) according to whether HBsAg turned negative when injection of PegIFNα -2b was stopped, and differences of HBsAg, ALT and AST between the two groups were compared respectively by generalized estimating equations. The influencing factors of HBsAg clearance were analyzed by multivariate Logistic regression model, and the influencing factors of HBsAg clearance were furtherly plotted into a receiver operating characteristic curve (ROC) to evaluate the predictive value.

Total of 45 patients were finally enrolled, 21 patients were completely treated with PegIFNα-2b for 48 weeks, among whom 10 cases were clinically cured (cure rate was 47.6%); while 24 patients were treated with premature termination of PegIFNα-2b, among whom 3 cases were clinically cured (cure rate was 12.5%). HBsAg decreased significantly compared with baseline of patients in both cured group and non-cured group (Z = -2.201, P = 0.028; Z =-3.17, P = 0.011). At the end of 48 weeks of enrollment, the level of ALT in cured group had no significant change compared with that of baseline (Z =-1.412, P = 0.158); However, there was a significant difference in level of AST compared with that of baseline (Z =-2.90, P = 0.004). The levels of ALT and AST of patients in non-cured group were not significantly different compared with those of baseline (Z =-1.97, P = 0.122; Z = -1.05, P = 0.421). Comparisons between groups: after adjusting of age and gender, there were no significant differences in ALT or AST at the end of 48 weeks of enrollment between patients of the two groups (χ² = 0.837, P = 0.36; χ² = 0.005, P = 0.945), but the level of HBsAg was significantly different (χ² = 24.161, P < 0.001). Multivariate Logistic regression analysis showed that baseline HBsAg (OR = 0.073, 95%CI: 0.007-0.803, P = 0.032), age (OR = 0.883, 95%CI: 0.781-00.998, P = 0.047) and treatment course of PegIFNα-2b (OR = 1.027, 95%CI: 1.001-1.053, P = 0.038) were all influencing factors for HBsAg clearance at 48 weeks. The area under ROC (AUC) for combination of baseline HBsAg, age and PegIFNα-2b was 0.978 (95%CI: 0.883-0.993), with the sensitivity and specificity as 96.44% and 88.95%, respectively.

PegIFNα-2b combination with NAs showed good clinical efficacy for CHB patients with low HBsAg level. Combination of baseline HBsAg, age and treatment course of PegIFNα-2b showed predictive value for HBsAg clearance at 48th week after treatment.