Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL.
Department of Pathology, The University of Chicago Medicine, Chicago, IL.
Hepatology. 2020 Jul;72(1):315-329. doi: 10.1002/hep.31227.
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoint molecules. ICIs are an immunotherapy for the treatment of many advanced malignancies. The advent of ICIs has been a major breakthrough in the field of oncology, a fact recognized by the 2018 Nobel Prize in Physiology or Medicine being awarded for the discovery. The Food and Drug Administration approved the first ICI, ipilimumab, in 2011 for the treatment of metastatic melanoma. Seven ICIs are now used in clinical practice, including nivolumab and pembrolizumab for treatment of advanced hepatocellular carcinoma. ICIs are increasingly used across the spectrum of hepatobiliary neoplasia. The utility of ICI therapy has been limited by immune-related adverse reactions (irAEs) affecting multiple organ systems. Hepatotoxicity is an important irAE, occurring in up to 16% of patients receiving ICIs. Optimizing outcomes in patients receiving ICI therapy requires awareness of and familiarity with diagnosing and management of ICI-induced immune-mediated hepatotoxicity (IMH), including approaches to treatment and ICI dose management. The aim of this review article is to (1) provide a comprehensive, evidence-based review of IMH; (2) perform a systematic review of the management of IMH; and (3) present algorithms for the diagnosis and management of IMH.
免疫检查点抑制剂（ICIs）是针对免疫检查点分子的单克隆抗体。ICI 是治疗多种晚期恶性肿瘤的免疫疗法。ICI 的出现是肿瘤学领域的重大突破，这一事实得到了 2018 年诺贝尔生理学或医学奖的认可，该奖项是为发现 ICI 而颁发的。美国食品和药物管理局于 2011 年批准了第一个 ICI（ipilimumab）用于治疗转移性黑色素瘤。目前有七种 ICI 用于临床实践，包括用于治疗晚期肝细胞癌的 nivolumab 和 pembrolizumab。ICI 在肝胆肿瘤的各个领域越来越多地被使用。ICI 治疗的应用受到影响多个器官系统的免疫相关不良反应（irAEs）的限制。肝毒性是一种重要的 irAE，在接受 ICI 治疗的患者中发生率高达 16%。为了优化接受 ICI 治疗的患者的结局，需要了解并熟悉诊断和管理 ICI 诱导的免疫介导的肝毒性（IMH），包括治疗方法和 ICI 剂量管理。本文的目的是：（1）提供 IMH 的全面、基于证据的综述；（2）对 IMH 的管理进行系统综述；（3）提出 IMH 的诊断和管理算法。
