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药物性肝损伤:最新进展。

Drug induced liver injury: an update.

机构信息

Unidad de Gestión Clínica de Aparato Digestivo y Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

出版信息

Arch Toxicol. 2020 Oct;94(10):3381-3407. doi: 10.1007/s00204-020-02885-1. Epub 2020 Aug 27.

Abstract

Drug induced liver injury (DILI) is a relatively rare hepatic condition in response to the use of medications, illegal drugs, herbal products or dietary supplements. It occurs in susceptible individuals through a combination of genetic and environmental risk factors believed to modify drug metabolism and/or excretion leading to a cascade of cellular events, including oxidative stress formation, apoptosis/necrosis, haptenization, immune response activation and a failure to adapt. The resultant liver damage can present with an array of phenotypes, which mimic almost every other liver disorder, and varies in severity from asymptomatic elevation of liver tests to fulminant hepatic failure. Despite recent research efforts specific biomarkers are not still available for routine use in clinical practice, which makes the diagnosis of DILI uncertain and relying on a high degree of awareness of this condition and the exclusion of other causes of liver disease. Diagnostic scales such as the CIOMS/RUCAM can support the causality assessment of a DILI suspicion, but need refinement as some criteria are not evidence-based. Prospective collection of well-vetted DILI cases in established DILI registries has allowed the identification and validation of a number of clinical variables, and to predict a more severe DILI outcome. DILI is also in need of properly designed clinical trials to evaluate the efficacy of new DILI treatments as well as older drugs such as ursodeoxycholic acid traditionally used to ameliorate cholestasis or corticosteroids now widely tried in the oncology field to manage the emergent type of hepatotoxicity related to immune checkpoint inhibitors.

摘要

药物性肝损伤(DILI)是一种相对罕见的肝脏疾病,是由药物、非法药物、草药产品或膳食补充剂引起的。易感个体在遗传和环境风险因素的共同作用下发生 DILI,这些因素被认为可以改变药物代谢和/或排泄,从而引发一系列细胞事件,包括氧化应激形成、细胞凋亡/坏死、半抗原化、免疫反应激活和适应失败。由此产生的肝损伤可能表现出多种表型,这些表型几乎可以模仿其他所有的肝脏疾病,并从无症状的肝试验升高到暴发性肝衰竭不等。尽管最近进行了研究,但仍没有特异性生物标志物可用于临床实践常规,这使得 DILI 的诊断不确定,需要高度警惕这种疾病,并排除其他肝脏疾病的原因。CIOMS/RUCAM 等诊断量表可以支持 DILI 怀疑的因果关系评估,但需要进一步完善,因为有些标准没有依据。在已建立的 DILI 登记处中,前瞻性收集经过严格审查的 DILI 病例,已经确定并验证了许多临床变量,并可以预测更严重的 DILI 结局。DILI 还需要进行精心设计的临床试验,以评估新的 DILI 治疗方法以及传统用于改善胆汁淤积的熊去氧胆酸等旧药物的疗效,目前在肿瘤学领域广泛尝试使用皮质类固醇来治疗与免疫检查点抑制剂相关的急性肝毒性。

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