Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
Deparment of Internal Medicine, Landspitali University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Clin Gastroenterol Hepatol. 2023 Jul;21(8):2088-2099. doi: 10.1016/j.cgh.2022.12.040. Epub 2023 Mar 1.
Idiosyncratic drug-induced liver injury (DILI) is an infrequent but important cause of liver disease. Newly identified causes of DILI include the COVID vaccines, turmeric, green tea extract, and immune checkpoint inhibitors. DILI is largely a clinical diagnosis of exclusion that requires evaluation for more common causes of liver injury and a compatible temporal association with the suspect drug. Recent progress in DILI causality assessment includes the development of the semi-automated revised electronic causality assessment method (RECAM) instrument. In addition, several drug-specific HLA associations have been identified that can help with the confirmation or exclusion of DILI in individual patients. Various prognostic models can help identify the 5%-10% of patients at highest risk of death. Following suspect drug cessation, 80% of patients with DILI fully recover, whereas 10%-15% have persistently abnormal laboratory studies at 6 months of follow-up. Hospitalized patients with DILI with an elevated international normalized ratio or mental status changes should be considered for N-acetylcysteine therapy and urgent liver transplant evaluation. Selected patients with moderate to severe drug reaction with eosinophilia and systemic symptoms or autoimmune features on liver biopsy may benefit from short-term corticosteroids. However, prospective studies are needed to determine the optimal patients and dose and duration of steroids to use. LiverTox is a comprehensive, freely accessible Web site with important information regarding the hepatotoxicity profile of more than 1000 approved medications and 60 herbal and dietary supplement products. It is hoped that ongoing "omics" studies will lead to additional insight into DILI pathogenesis, improved diagnostic and prognostic biomarkers, and mechanism-based treatments.
特发性药物性肝损伤 (DILI) 是一种罕见但重要的肝病病因。新发现的 DILI 病因包括 COVID 疫苗、姜黄、绿茶提取物和免疫检查点抑制剂。DILI 主要是一种排除性的临床诊断,需要评估更常见的肝损伤病因,并与可疑药物有相容的时间关联。DILI 因果关系评估的最新进展包括开发半自动修订电子因果关系评估方法 (RECAM) 仪器。此外,已经确定了几种特定药物的 HLA 相关性,可帮助在个体患者中确认或排除 DILI。各种预后模型有助于识别出 5%-10%的死亡风险最高的患者。停止可疑药物后,80%的 DILI 患者完全康复,而 10%-15%的患者在 6 个月的随访中仍存在实验室检查异常。国际标准化比值升高或精神状态改变的 DILI 住院患者应考虑使用 N-乙酰半胱氨酸治疗和紧急肝移植评估。肝活检显示中度至重度药物反应伴嗜酸性粒细胞增多和全身症状或自身免疫特征的选定患者可能受益于短期皮质类固醇治疗。然而,需要前瞻性研究来确定最佳患者以及使用皮质类固醇的剂量和持续时间。LiverTox 是一个综合性的、免费获取的网站,提供了 1000 多种已批准药物和 60 种草药和膳食补充剂产品的肝毒性特征的重要信息。人们希望正在进行的“组学”研究将为 DILI 发病机制、改进的诊断和预后生物标志物以及基于机制的治疗提供更多的见解。
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