Mon Hsien-Chen, Lee Pei-Chang, Hung Yi-Ping, Hung Ya-Wen, Wu Chi-Jung, Lee Chieh-Ju, Chi Chen-Ta, Lee I-Cheng, Hou Ming-Chih, Huang Yi-Hsiang
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
J Hepatol. 2025 Jan;82(1):51-61. doi: 10.1016/j.jhep.2024.07.018. Epub 2024 Jul 29.
BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) can restore exhausted T-cell immunity not only for cancer treatment but also potentially to cure chronic hepatitis B (CHB). Thus, we aimed to determine the previously unclear impact of ICIs on hepatitis B surface antigen (HBsAg) seroclearance in patients with cancer.
Consecutive patients with cancer from 2016 to 2020 (cohort 1, n = 118), and hepatocellular carcinoma from 2020 to 2022 (cohort 2, n = 44, as validation) receiving ICIs and positive for HBsAg were retrospectively recruited. An additional HBV-HCC cohort (cohort 3, n = 85) not receiving ICIs served as a control group. Factors associated with HBsAg loss or a HBsAg decline >1 log were analyzed.
With median follow-up of 17.5 months, 8 (6.8%) patients in cohort 1 and 4 (9.1%) in cohort 2 achieved HBsAg seroclearance, and an additional four in cohort 1 and one in cohort 2 had a HBsAg decline >1 log. In multivariate analysis, HBsAg <100 IU/ml was associated with HBsAg seroclearance (hazard ratio 6.274, p = 0.028). In the validation cohort, the cumulative incidences of HBsAg loss at months 12 and 24 were 13.0% and 38.4%, respectively, for baseline HBsAg <100 IU/ml, which were significantly higher than those in the control group (p = 0.0267). No case in cohort 3 achieved HBsAg loss within 24 months. Of the 17 cases who achieved HBsAg loss or a decline >1 log, 16 (94.1%) received nucleos(t)ide analogue treatment. The median time to HBsAg loss or HBsAg decline was 16.5 (range 9.6 to 27.5) months.
ICIs may accelerate HBsAg seroclearance in patients with cancer and baseline HBsAg <100 IU/ml. This finding provides important information for the design of future trials evaluating the ability of ICIs to induce functional cure in patients with CHB.
Immune checkpoint inhibitors (ICIs) can restore exhausted T-cell immunity not only for cancer treatment but also potentially to cure chronic hepatitis B. Functional cure of hepatitis B was observed in patients with cancer or HCC undergoing ICI treatment, and the cumulative incidence of HBsAg loss was higher compared with controls without ICIs. ICIs may accelerate the HBsAg loss in patients with baseline HBsAg levels <100 IU/ml. This finding provides important information for the design of future ICI trials evaluating the ability of ICIs to induce functional cure in patients with CHB.
免疫检查点抑制剂（ICIs）不仅可恢复耗竭的T细胞免疫用于癌症治疗，还可能治愈慢性乙型肝炎（CHB）。因此，我们旨在确定ICIs对癌症患者乙肝表面抗原（HBsAg）血清学清除的影响，此前这一影响尚不清楚。
回顾性纳入2016年至2020年连续的癌症患者（队列1，n = 118）以及2020年至2022年的肝细胞癌患者（队列2，n = 44，作为验证队列），这些患者接受ICIs治疗且HBsAg呈阳性。另外选取未接受ICIs治疗的HBV-HCC队列（队列3，n = 85）作为对照组。分析与HBsAg消失或HBsAg下降>1 log相关的因素。
中位随访17.5个月，队列1中有8例（6.8%）患者、队列2中有4例（9.1%）患者实现了HBsAg血清学清除，队列1中另有4例、队列2中另有1例患者的HBsAg下降>1 log。多因素分析显示，HBsAg<100 IU/ml与HBsAg血清学清除相关（风险比6.274，p = 0.028）。在验证队列中，基线HBsAg<100 IU/ml者在第12个月和第24个月时HBsAg消失的累积发生率分别为13.0%和38.4%，显著高于对照组（p = 0.0267）。队列3中无病例在24个月内实现HBsAg消失。在实现HBsAg消失或下降>1 log的17例患者中，16例（94.1%）接受了核苷（酸）类似物治疗。HBsAg消失或下降的中位时间为16.5（9.6至27.5）个月。
ICIs可能会加速癌症且基线HBsAg<100 IU/ml患者的HBsAg血清学清除。这一发现为未来评估ICIs诱导CHB患者功能性治愈能力的试验设计提供了重要信息。
免疫检查点抑制剂（ICIs）不仅可恢复耗竭的T细胞免疫用于癌症治疗，还可能治愈慢性乙型肝炎。在接受ICI治疗的癌症或HCC患者中观察到了乙肝的功能性治愈，与未接受ICIs治疗的对照组相比，HBsAg消失的累积发生率更高。ICIs可能会加速基线HBsAg水平<100 IU/ml患者的HBsAg消失。这一发现为未来评估ICIs诱导CHB患者功能性治愈能力的ICI试验设计提供了重要信息。
