免疫检查点抑制剂致肝损伤的研究进展

免疫检查点抑制剂（immune checkpoint inhibitors，ICPi）靶向作用于细胞毒性T淋巴细胞相关抗原4（cytotoxic T-lymphocyte-associated antigen 4，CTLA-4）和程序性死亡受体/配体1（programmed death-1/ligand，PD-1/PD-L1），提高了多种类型恶性肿瘤患者的生存率。然而，随着ICPi临床应用日益增多，免疫相关不良反应（immune-related adverse events，irAEs）的报道也越来越多。肝损伤为其常见的irAEs之一，其发生的危险因素涉及ICPi药物种类、肿瘤类型、联用酪氨酸激酶抑制剂（tyrosine kinase inhibitors，TKIs）和非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）等。ICPi致肝损伤最常见的临床表现为无症状的丙氨酸氨基转移酶（alanine aminotransferase，ALT）升高和天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）升高，具有复杂、多样化的组织学形态特征。治疗时以糖皮质激素治疗为主，必要时可加用免疫抑制剂麦考酚酯。

Research progress of immune checkpoint inhibitors-induced liver injury

Immune checkpoint inhibitors(ICPi)targeted against cytotoxic T-lymphocyte-associated antigen 4(CTLA-4)and programmed death-1/ligand(PD-1/PD-L1)have improved the survival rate of patients with various malignant tumors.However,with the increasing clinical use of ICPi,immune-related adverse events(irAEs)are increasingly reported.Liver injury is one of its common irAEs,and the risk factors for its occurrence involve the type of ICPi drug,tumor type,combination of tyrosine kinase inhibitors(TKIs)and non-alcoholic fatty liver disease(NAFLD).The most common clinical manifestations of ICPi-induced liver injury are asymptomatic elevated alanine aminotransferase(ALT)and elevated aspartate aminotransferase(AST)with complex and diverse histological morphological features.The treatment is mainly glucocorticoid therapy,and the immunosuppressant mycophenolate can be added when necessary.