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药物性肝损伤的流行病学与管理:更新版RUCAM的重要性

Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM.

作者信息

Kobayashi Takashi, Iwaki Michihiro, Nogami Asako, Yoneda Masato

机构信息

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

出版信息

J Clin Transl Hepatol. 2023 Oct 28;11(5):1239-1245. doi: 10.14218/JCTH.2022.00067S. Epub 2023 Apr 28.

Abstract

Drug-induced liver injury (DILI) is a major cause of acute liver injury, liver failure, and liver transplantation worldwide. In recent years, immune checkpoint inhibitors have become widely used. This has led to an increase in DILI, for which pathophysiology and management methods differ significantly from the past. As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase, information about a DILI is becoming more valuable. DILI is classified into two types according to its etiology: intrinsic DILI, in which the drug or its metabolites cause liver damage that is dose-dependent and predictable; and idiosyncratic DILI, in which liver damage is also dose-independent but unpredictable. In addition, depending on the course of the disease, chronic DILI or drug-induced autoimmune hepatitis may be present. The number of DILI cases caused by antimicrobial agents is decreasing, whereas that caused by drugs for malignant tumors and health foods is increasing. The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI. Liver injury is a type of immune-related adverse event. The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular, but mixed type and bile stasis have also been reported. Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury. Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration; however, mycophenolate mofetil may be considered if the disease is refractory to steroids.

摘要

药物性肝损伤(DILI)是全球急性肝损伤、肝衰竭和肝移植的主要原因。近年来,免疫检查点抑制剂已被广泛使用。这导致了DILI病例的增加,其病理生理学和管理方法与过去有显著差异。由于预计因DILI导致的急性肝损伤和肝移植病例数量将会增加,有关DILI的信息变得越来越有价值。DILI根据其病因分为两种类型:内在性DILI,即药物或其代谢产物导致的肝损伤呈剂量依赖性且可预测;以及特异质性DILI,即肝损伤也是非剂量依赖性但不可预测的。此外,根据疾病进程,可能存在慢性DILI或药物性自身免疫性肝炎。由抗菌药物引起的DILI病例数量正在减少,而由用于恶性肿瘤的药物和保健食品引起的病例数量正在增加。Roussel Uclaf因果关系评估方法被广泛用于评估DILI中的因果关系。肝损伤是一种免疫相关不良事件。免疫相关不良事件中的肝损伤模式大多为肝细胞性,但也有混合型和胆汁淤积的报道。由免疫检查点抑制剂引起的硬化性胆管炎也被报道为一种独特的损伤类型。治疗主要包括停用免疫检查点抑制剂和给予类固醇;然而,如果疾病对类固醇难治,可考虑使用霉酚酸酯。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e89d/10412691/52c291329261/JCTH-11-1239-g001.jpg

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