背景：免疫检查点抑制剂（ICIs），包括抗PD-1、抗PD-L1和抗CTLA-4抗体，已成为多种癌症类型的标准治疗方法。然而，ICIs 可诱发免疫相关不良事件，其中肝炎相关不良事件 (HRAE) 特别值得关注。我们的目标是使用真实世界数据来识别和表征与 ICI 显着相关的 HRAE。方法：在这项观察性和回顾性药物警戒研究中，我们从 FDA 不良事件报告系统数据库中提取了 2004 年第一季度至 2023 年第一季度的真实不良事件报告。我们在框架中同时采用了频率论和贝叶斯方法。不成比例分析，其中包括报告比值比 (ROR) 和信息成分 (IC)，以探索 ICI 和 HRAE 之间的复杂关系。结果：通过不成比例分析，我们确定了三类与 ICI 显着相关的 HRAE，包括自身免疫性肝炎（634 例，ROR 19.34 [95% CI 17.80-21.02]；IC025 2.43）、免疫介导的肝炎（546 例，ROR） 217.24 [189.95-248.45]；IC025 4.75）和暴发性肝炎（80 例，ROR 4.56 [3.65-5.70]；IC025 0.49）。报告 ICI 相关 HRAE 的患者中位年龄为 63 岁（四分位数范围 [IQR] 53.8-72），其中 24.9% (313/1,260) 的报告观察到致命结果。其中大部分病例与皮肤癌、肺癌和肾癌有关。与接受抗 CTLA-4 单一疗法的患者相比，接受抗 PD-1 或​​抗 PD-L1 抗体治疗的患者出现免疫介导的肝炎的频率更高，ROR 为 3.59 (95% CI 1.78-6.18)。此外，与 ICI 单药治疗相比，双重 ICI 治疗显示出更高的 ICI 相关 HRAE 报告率。结论：我们的研究结果证实，ICI 治疗存在严重 HRAE 的显着风险，特别是自身免疫性肝炎、免疫介导的肝炎和暴发性肝炎。医疗保健提供者在管理接受 ICI 的患者时应对这些风险保持高度警惕。版权所有 © 2024 Fu、Liu、Zhang、Hu、Li、Zhang 和 You。

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80-21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95-248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65-5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8-72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78-6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.Copyright © 2024 Fu, Liu, Zhang, Hu, Li, Zhang and You.