免疫检查点抑制剂相关胆管型肝毒性发生机制及治疗策略

Mechanism and treatment strategies of immune checkpoint inhibitors related biliary type hepatotoxicity

肿瘤免疫检查点抑制剂(ICI)治疗近年来因疗效显著而备受瞩目。ICI引起的免疫介导肝毒性(IMH)是一类较常见的免疫相关不良反应(irAE),但IMH中的一种亚分型,胆管型IMH(BIMH),却是一种少见的、对其认知极不充分、缺乏诊疗规范的irAE,存在临床隐患。BIMH以胆管酶显著升高、高胆红素血症为临床特点,组织病理学表现为胆管炎症、胆管损伤和消失。胆汁淤积阶段的BIMH对于免疫抑制治疗反应不佳,预后差。提高对BIMH的认识,早期诊断和干预是提高BIMH预后的关键。对BIMH流行病学特征、临床特征、组织病理学特点和发生机制及BIMH全程管理中存在之问题等认识的不断提高,有助于提出针对BIMH的有效诊疗策略。

Immune checkpoint inhibitors(ICIs)have attracted much attention in recent years due to their remarkable efficacy in tumor treatment.Immune mediated hepatotoxicity(IMH)caused by ICIs is a kind of common immune related adverse events(irAEs).However,a subtype of IMH,biliary type IMH(BIMH)is a rare irAE with insufficient cognition and lack of standardized diagnosis and treatment,which has hidden clinical dangers.The patient with BIMH is characterized by significant increase of bile duct enzymes and hyperbilirubinemia.The histopathological manifestations of BIMH are bile duct inflammation,bile duct injury and disappearance.The patients with BIMH in cholestasis stage have poor response to immunosuppressive therapy and their prognoses are poor.Improving the understanding of BIMH,early diagnosis and early intervention are the keys to improve the prognosis of patients with BIMH.Constant understanding of the epidemiological characteristics,clinical characteristics,histopathological characteristics,pathogenesis and problems in the overall management of BIMH will help to put forward more effective diagnosis and treatment strategies for BIMH.