免疫检查点抑制剂所致免疫介导性肝损伤研究进展  

Research progress of immune‑mediated liver injury induced by immune checkpoint inhibitors

作　　者：王艳[1] 赵新颜[1] 贾继东[1] Wang Yan;Zhao Xinyan;Jia Jidong(Liver Research Center,Beijing Friendship Hospital,Capital Medical University,National Clinical Research Center for Digestive Diseases,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院肝病中心,国家消化系统疾病临床医学研究中心,北京100050

出　　处：《药物不良反应杂志》2023年第4期243-247,共5页Adverse Drug Reactions Journal

基　　金：国家自然科学基金(81900526)。

摘　　要：免疫检查点抑制剂(ICI)通过激活人体免疫系统发挥抗肿瘤治疗作用,但可引起免疫介导性肝损伤。ICI引起的免疫介导性肝损伤在发生率、临床表现、发病机制和预后等方面均与经典药物性肝损伤不同。其主要发病机制是由于ICI阻断了负向免疫调节的关键节点,包括细胞毒性T淋巴细胞相关抗原⁃4或程序性细胞死亡1受体/程序性细胞死亡配体1,在过度激活的免疫系统作用下失去对肝脏的免疫耐受而发生肝损伤。免疫介导性肝损伤可分为免疫介导性肝炎和免疫介导性胆管炎。肝脏组织病理学检查可见肝细胞及胆管的损伤,多有中央静脉内皮炎,可有肉芽肿性病变。诊断免疫介导性肝损伤后应根据肝损伤严重程度分级选择治疗方案,多需糖皮质激素或免疫抑制剂治疗。Immune checkpoint inhibitors(ICIs)play the role of anti⁃tumor by activating the immune system in human,but they can also cause immune⁃mediated liver injury,which is different from conventional drug⁃induced liver injury in the incidence,clinical manifestations,pathogenesis,and prognosis.The main pathogenesis is that ICIs block key nodes of negative regulation of the immune response,including cytotoxic T⁃lymphocyte⁃associated antigen 4 and programmed cell death 1 receptor/programmed cell death ligand 1.Liver⁃injury occurs when the immune system is overactivated and loses immune tolerance to the liver.Immune⁃mediated liver injury includes immune⁃mediated hepatitis and immune⁃mediated cholangitis.Histopathological examination of the liver shows damage in hepatocytes and bile ducts,accompanied by central venous dermatitis mostly and granulomatous lesions partially.After diagnosis of immune⁃mediated liver injury,treatment should be given based on the severity,and glucocorticoids or immunosuppressants are often necessary.

关 键 词：免疫检查点抑制剂 抗肿瘤药 药物性肝损伤 程序性细胞死亡1受体 程序性细胞死亡配体1 细胞毒性T淋巴细胞相关抗原-4 

分 类 号：R575[医药卫生—消化系统]