Abstract: Objective The aim of this study was to analyze the efficacy and safety of sequential combination of nucleos(t)ide analogs (NAs) with peginterferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB) with low serum HBsAg levels. Methods A total of 106 CHB patients with serum HBsAg levels less than 1500 IU/mL after NAs treatment were enrolled in our hospital between November 2015 and October 2018. 42 patients were given sequential combination therapy of NAs and Peg-IFNα-2a/2b for 48 weeks, and 64 patients were continuously treated with NAs who had always taken. All patients were followed-up to week 96 (48 weeks after discontinuation of Peg-IFN-α). Results Two patients in the sequential combination group and 4 patients in the NAs group were lost; the intention- to-treat (ITT) analysis showed that the baseline materials in the two groups were comparable; serum HBsAg clearance rate and anti-HBs seroconversion rate in the sequential combination group were 19.0% and 14.3% at the end of 48-week treatment, both significantly higher than 0.0% and 0.0%, respectively, in the NAs group (P <0.001); the rates of serum HBsAg clearance and anti-HBs seroconversion at the end of 48-week follow-up in the sequential combination group were 21.4% and 19.0%, both significantly higher than 1.6% and 1.6%,respectively (P <0.001)in the NAs group; the liver stiffness measurement (LSM) was (7.2±0.3) kPa, significantly lower than in the NAs group, Conclusion The sequential combination of NAs and Peg-IFN-α treatment ameliorate serum HBsAg clearance and seroconversion, which might improve liver fibrosis in CHB patients with low levels of HBsAg, and gain clinical recovery.

Key words: Hepatitis B, Peginterferon alpha, Nucleos(t)ide analogs, Sequential combination, Serum HBsAg clearance