Twenty-four-week anti-PD-1 antibody regimen promoted HBsAg reduction and concurrently enhanced HBV-specific T cell responses in patients with chronic hepatitis B

作者：Taiyu He, Min Chen, Maoying Liu, L Zhang, Huidan Sun, L Zhang, Aoyi Li, Weiqun Zeng, Ning Ling, Xiaofeng Shi, Hua He, Mingli Peng, Dachuan Cai, Peng Hu, Dazhi Zhang, Yinghua Lan, Hong Ren · 发表于：Gut · 年份：2025 · DOI：10.1136/gutjnl-2025-336655 · 被引用次数：5 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Liver Diseases and Immunity

BACKGROUND: PD-1 blockade has emerged as a promising approach for functional cure of chronic hepatitis B (CHB). OBJECTIVE: This study aimed to evaluate the safety profile of anti-PD-1 antibody (αPD-1), as well as its impact on hepatitis B surface antigen (HBsAg) and immune responses in a larger cohort of CHB patients. DESIGN: In this prospective, open-label study, virally suppressed patients with CHB on nucleos(t)ide analogue (NA) were assigned to receive either 24-week NA monotherapy (n=62) or αPD-1 (half-dose sintilimab) add-on therapy (n=59), with both groups subsequently receiving NA monotherapy for an additional 12-week observation period. RESULTS: IU/mL, p<0.001) and higher HBsAg loss rates (6.1% vs 0%, p=0.166) than NA monotherapy at week 24. Notably, significant HBsAg decline and seroclearance exclusively occurred in the initial 12 weeks of αPD-1 treatment. HBsAg levels did not rebound at 12 weeks after discontinuation of αPD-1 therapy. After αPD-1 therapy, the numbers of HBsAg-specific, HBpol-specific, HBx-specific and HBeAg/HBcAg-specific IFN-γ spots all increased (p<0.05), while frequencies of HBsAg-specific B cells remained stable. Furthermore, ALT elevation and enhanced HBsAg-specific T-cell responses following αPD-1 therapy correlated with HBsAg decline (p<0.05). CONCLUSIONS: In virally suppressed CHB patients on NA therapy, 24-week half-dose sintilimab treatment demonstrated a favourable safety profile. This regimen can facilitate HBsAg reduction and even HBsAg...