Liu Zherui, Zhu Yun, Xie Huan, Zou Zhengsheng
Medical School of Chinese PLA, Beijing, China.
Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China.
Front Pharmacol. 2023 Jan 9;13:1077468. doi: 10.3389/fphar.2022.1077468. eCollection 2022.
In recent years, cancer immunotherapy has made remarkable achievements. Immune checkpoint inhibitors (ICIs) have been used successfully in several types of cancer in the past decade. However, expanded indication and increased use of Immune checkpoint inhibitors have resulted in increased reports of toxicity called immune-related adverse events (irAEs). Due to the unique immunological characteristics of the liver, a hepatic immune-related adverse events has also been reported, which is usually termed Immune-mediated hepatitis (IMH). So far, it is generally considered that the mechanism of IMH induced by Immune checkpoint inhibitors is mainly the overactivation of T cells. It has been reported that the incidence of IMH ranges from 1% to 15%. Because of the lack of specific markers, a diagnosis of exclusion of IMH is critical. Although most IMH is mild and recoverable, several death cases have been reported, which has been increasingly concerned. This review summarizes the current understanding of the pathophysiology, epidemiology, diagnosis, management and prognosis of IMH caused by Immune checkpoint inhibitors. It also discusses the controversial issues in IMH, such as the role of liver biopsy, grading criteria, risk factors, rational treatment strategies with steroids, and the timing of Immune checkpoint inhibitors rechallenging, which may provide helpful information for IMH in future clinical practice.
近年来，癌症免疫疗法取得了显著成就。在过去十年中，免疫检查点抑制剂（ICIs）已成功应用于多种类型的癌症。然而，免疫检查点抑制剂适应证的扩大和使用的增加导致了称为免疫相关不良事件（irAEs）的毒性报告增多。由于肝脏独特的免疫学特性，也有肝免疫相关不良事件的报道，通常称为免疫介导性肝炎（IMH）。迄今为止，普遍认为免疫检查点抑制剂诱导IMH的机制主要是T细胞过度活化。据报道，IMH的发生率为1%至15%。由于缺乏特异性标志物，排除性诊断IMH至关重要。尽管大多数IMH症状轻微且可恢复，但已有数例死亡病例报道，这一情况日益受到关注。本综述总结了目前对免疫检查点抑制剂所致IMH的病理生理学、流行病学、诊断、管理及预后的认识。还讨论了IMH中存在争议的问题，如肝活检的作用、分级标准、危险因素、类固醇的合理治疗策略以及免疫检查点抑制剂再次使用的时机等，这可能为未来临床实践中IMH的诊治提供有益信息。
