Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
J Viral Hepat. 2024 Dec;31(12):847-856. doi: 10.1111/jvh.14007. Epub 2024 Sep 9.
Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow-up data was retrieved in 7833 antiviral-treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB-infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death-1 (PD-1) expression and proportion of regulatory T cells (CD4CD25CD127). Effector function of HBV-specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFβ) production in undepleted PBMCs and Treg-depleted PBMCs after 7 days in vitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow-up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57-0.87). PD-1 expression was increased in CD4 T cells, CD8 T cells and CD20 B cells among smokers compared to non-smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV-specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non-smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD-1 expression on lymphocytes, and impairment of effector functions of HBV-specific T cells in CHB.
吸烟与慢性乙型肝炎（CHB）感染患者的临床结局恶化相关，但对乙型肝炎表面抗原（HBsAg）血清学清除的影响尚不清楚。本研究旨在探讨主动吸烟对 CHB 感染患者 HBsAg 血清学清除（SC）的影响及其对外周血淋巴细胞的影响。从集中电子患者记录数据库中检索了 7833 例接受抗病毒治疗的 CHB 患者的纵向随访数据（第 1 部分）。通过流式细胞术对 27 例 CHB 感染患者（6 例为主动吸烟者；13 例 HBsAg 清除者）的外周血单个核细胞（PBMC）进行表型分析，以评估程序性死亡-1（PD-1）表达和调节性 T 细胞（CD4CD25CD127）的比例。通过比较 HBV 包膜蛋白重叠肽体外刺激 7 天后未耗竭 PBMC 和 Treg 耗竭 PBMC 中颗粒酶 B（GZMB）和转化生长因子β（TGFβ）的产生，来检测 HBV 特异性 T 细胞的效应功能（第 2 部分）。在中位随访 5 年内，吸烟与 HBsAg 清除的可能性降低相关（aHR 0.70，95%CI 0.57-0.87）。与非吸烟者相比，吸烟者的 CD4 T 细胞、CD8 T 细胞和 CD20 B 细胞中 PD-1 表达增加，且与吸烟年数呈正相关（均 p<0.05）。Treg 耗竭导致 HBV 特异性 T 细胞的部分功能恢复，吸烟者的恢复幅度明显大于非吸烟者（p=0.0451，平均差异=4.68%；p=0.012，平均差异=4.2%）。吸烟与 HBsAg 血清学清除率降低、淋巴细胞 PD-1 表达升高以及 CHB 患者 HBV 特异性 T 细胞效应功能受损相关。
