免疫检查点抑制剂 (ICIs) 可以恢复耗尽的 T 细胞免疫力，不仅可以用于癌症治疗，还可以用于治疗慢性乙型肝炎 (CHB)。 ICI 对癌症患者乙型肝炎表面抗原 (HBsAg) 血清清除的影响尚不清楚。 2016 年至 2020 年连续癌症患者（队列 1，n=118），以及 2020 年至 2022 年肝细胞癌 (HCC) 患者（队列 2，回顾性招募接受 ICI 且 HBsAg 呈阳性的 n=44（作为验证）。另外一个没有 ICI 的乙型肝炎病毒 (HBV)-HCC 队列（队列 3，n=85）作为对照组。分析了与 HBsAg 消失或 HBsAg 下降 > 1 log 相关的因素。中位随访时间为 17.5 个月，队列 1 中的 8 名患者 (6.8%) 和队列 2 中的 4 名患者 (9.1%) 实现了 HBsAg 血清清除，队列中另外 4 名患者实现了 HBsAg 血清清除。第 2 组中的 1 号和 1 号 HBsAg 下降 >1 个对数。在多变量分析中，HBsAg <100 IU/mL 与 HBsAg 血清清除相关（HR=6.274，p=0.028）。在验证队列中，基线 HBsAg <100 IU/ml 时，第 12 个月和第 24 个月的 HBsAg 消失累积发生率分别为 13.0% 和 38.4%，显着高于对照组 (p=0.0267)。而第 3 组中没有病例在 24 个月内达到 HBsAg。在 17 例 HBsAg 消失和下降>1 log 的病例中，16 例 (94.1%) 接受了核苷（酸）类似物治疗。 HBsAg 消失或 HBsAg 下降的中位时间为 16.5 个月（范围为 9.6 至 27.5）。ICIs 可能会加速基线 HBsAg <100 IU/ml 的癌症患者的 HBsAg 血清清除。这一发现为未来 ICI 试验的设计提供了重要信息，以实现 CHB 患者的功能性治愈。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Immune checkpoint inhibitors (ICIs) can restore exhausted T cell immunity not only for cancer treatment but also potentially for curing chronic hepatitis B (CHB). The impact of ICIs on Hepatitis B surface antigen (HBsAg) seroclearance in cancer patients was unclear.Consecutive cancer patients from 2016 to 2020 (Cohort 1, n=118), and hepatocellular carcinoma (HCC) patients from 2020 to 2022 (Cohort 2, n=44, as validation) receiving ICIs and positive for HBsAg were retrospectively recruited. An additional hepatitis B virus (HBV)-HCC cohort (Cohort 3, n=85) without ICI served as a control group. Factors associated with HBsAg loss or combining HBsAg decline >1 log were analyzed.With median follow-up of 17.5 months, 8 (6.8%) in cohort 1 and 4 (9.1%) in cohort 2 achieved HBsAg seroclearance, and additional 4 in cohort 1 and 1 in cohort 2 had HBsAg decline >1 log. In multivariate analysis, HBsAg <100 IU/mL was associated with HBsAg seroclearance (HR=6.274, p=0.028). In the validation cohort, the cumulative incidence of HBsAg loss at months 12 and 24 was 13.0% and 38.4% for baseline HBsAg <100 IU/ml, which were significantly higher than those in the control group (p=0.0267). While no case in cohort 3 achieved HBsAg within 24 months. Of the 17 cases achieved HBsAg loss and decline >1 log, 16 (94.1%) had nucleos(t)ide analogs treatment. The median time to HBsAg loss or HBsAg decline was 16.5 months (ranged 9.6 to 27.5).ICIs may accelerate HBsAg seroclearance in cancer patients with baseline HBsAg <100 IU/ml. This finding provides important information for the design of future ICI trials to achieve functional cure in patients with CHB.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.