Bessone Fernando, Bjornsson Einar Stefan
Department of Gastroenterology and Hepatology, Facultad de Ciencias Médicas, Hospital Provincial del Centenario, University of Rosario School of Medicine, Rosario 2000, Santa Fe, Argentina.
Department of Gastroenterology, Natl Univ Hosp Iceland, Sect Gastroenterol & Hepatol, Dept Internal Med, Hringbraut 11D, IS-101 Reykjavik, Iceland.
World J Hepatol. 2022 Jul 27;14(7):1269-1276. doi: 10.4254/wjh.v14.i7.1269.
Immunological checkpoint inhibitors (ICIs) have revolutionized therapy of many different malignanices. Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin, lungs, gastrointestinal and endocrine organs as well as the liver. Liver injury has been reported in 3%-8% of patients with grade III-IV hepatitis in retrospective studies. The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation. The role for liver biopsy (LB) in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management. LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected. Although there are no distinctive histological features, the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs. The natural history of hepatotoxicity of ICI therapy is not well known. Recent studies have demonstrated that 33%-50% of patients improve spontaneously with discontinuation of ICIs. In patients with jaundice and/or coagulopathy corticosteroids are used. The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial. Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens. Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.
免疫检查点抑制剂（ICIs）彻底改变了许多不同恶性肿瘤的治疗方法。伴随的免疫介导的不良反应很常见，可影响许多器官，如皮肤、肺、胃肠道、内分泌器官以及肝脏。回顾性研究报告称，3%-8%的患者出现III-IV级肝炎时会发生肝损伤。肝损伤的特征是肝细胞损伤，在生化方面类似于自身免疫性肝炎，但在免疫方面并非如此，因为ICI诱导的肝毒性患者很少有自身抗体或IgG升高。肝活检（LB）在疑似因ICI导致肝损伤的患者中的作用存在争议，目前尚不清楚LB的结果是否会改变临床管理。当存在诊断不确定性且怀疑有既往肝病时，LB可能会有所帮助。虽然没有独特的组织学特征，但发现肉芽肿和血管内皮炎可能提示ICI诱导的特定类型的肝炎。ICI治疗肝毒性的自然病程尚不清楚。最近的研究表明，33%-50%的患者在停用ICI后会自发改善。对于黄疸和/或凝血功能障碍的患者，使用皮质类固醇。肿瘤学会推荐的高剂量皮质类固醇，即1-2mg/kg/d的甲泼尼龙，存在争议。最近的研究表明，与高剂量方案相比，初始剂量为1mg/kg/d的治疗可使肝功能检查得到类似改善，且与类固醇诱导的不良反应风险降低相关。据报道，主要使用霉酚酸酯进行的二级免疫抑制是有帮助的。
