Abstract: Objective The aim of this study was to compare the efficacy of re-treatment of chronic hepatitis B (CHB) non-responders to pegylated interferon-α by tenofovir and entecavir. Methods 77 patients with CHB who were the non-responders to pegylated interferon-α were recruited in our hospital between June 2016 and March 2020, and divided into two groups, receiving tenofovir (n=41) or entecavir (n=36), respectively. Serum HBV DNA and HBsAg and HBeAg were assayed routinely, and peripheral blood lymphocyte subsets was detected by FCM. Results At the end of six and twelve month treatment, serum alanineaminotransferase normalization rates in tenofovir-treated patients were 80.5% and 90.2%, not significantly different as compared to 77.8% and 86.1% in entecavir-treated patients(P＞0.05), serum HBV DNA loss were 65.9% and 95.1%, also not significantly different as compared to 63.9% and 88.9% (P＞0.05) in entecavir-treated patients; the percentage of peripheral blood CD4⁺ cells in tenofovir-treated patients were(33.9±3.9)% and (38.6±5.6)%, significantly higher than , and the CD4⁺/CD8⁺ cell ratio were (1.2±0.1) and (1.5±0.1), significantly higher than [(1.0±0.0) and (1.3±0.1), respectively, P＜0.05] in entecavir-treated patients; during the 12-month observation period, the resistance rate in tenofovir-treated patients was 4.9%, not significantly different compared to 2.8% in entecavir-treated patients (x²=0.013,P=0.908). Conclusion The administration of tenofovir and entecavir in the treatment of CHB patients who do not respond to polyethylene glycol interferon-α could obtain a good clinical efficacy, while the tenofovir could improve immune functions, which might improve serological response and warrants further investigation.

Key words: Hepatitis B, Tenofovir, Entecavir, Pegylated interferon-α, Re-treatment