Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Department of Internal Medicine and Dermatology, University of Michigan, Ann Arbor, Michigan.
Semin Liver Dis. 2018 Nov;38(4):366-378. doi: 10.1055/s-0038-1667358. Epub 2018 Oct 24.
Immune checkpoint inhibition targeted against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has shown clinically significant survival benefit when used to treat multiple types of advanced cancer. These drugs have gained approval by the US Food and Drug Administration and their indications continue to increase. Checkpoint inhibitor therapy is associated with a unique side-effect profile characterized as immune-related adverse events (irAEs), which can result in significant morbidity and rarely mortality. Hepatotoxicity from checkpoint inhibitors is a less common irAE and often mild, while its incidence and severity vary based on the class and dose of checkpoint inhibitor, monotherapy versus combination therapy, and the type of cancer. Histological assessment of suspected irAEs is nonspecific and can show a variety of features. Hepatic irAEs can require discontinuation of checkpoint inhibitor therapy and treatment with immunosuppressive agents.
免疫检查点抑制剂针对细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)和程序性细胞死亡蛋白 1(PD-1)的抑制作用,在治疗多种晚期癌症时显示出具有临床意义的生存获益。这些药物已获得美国食品和药物管理局的批准,其适应证不断增加。检查点抑制剂治疗与独特的副作用谱相关,其特征为免疫相关不良事件(irAEs),可导致严重发病率,且罕见死亡。检查点抑制剂引起的肝毒性是一种不太常见的 irAE,通常为轻度,但其发生率和严重程度取决于检查点抑制剂的类别和剂量、单药治疗与联合治疗、以及癌症的类型。疑似 irAEs 的组织学评估是非特异性的,可能显示出多种特征。肝 irAEs 可能需要停止检查点抑制剂治疗,并使用免疫抑制剂治疗。