Division of Gastroenterology and Hepatology, Georgetown University Hospital, Washington, DC, USA.
Department of Medicine, Georgetown University Hospital, Washington, DC, USA.
Drug Saf. 2019 Mar;42(3):365-387. doi: 10.1007/s40264-018-0743-2.
Drug-induced liver injury (DILI), herbal-induced liver injury, and herbal and dietary supplement (HDS)-induced liver injury are an important aspect of drug safety. Knowledge regarding responsible drugs, mechanisms, risk factors, and the diagnostic tools to detect liver injury have continued to grow in the past year. This review highlights what we considered the most significant publications from among more than 1800 articles relating to liver injury from medications, herbal products, and dietary supplements in 2017 and 2018. The US Drug-Induced Liver Injury Network (DILIN) prospective study highlighted several areas of ongoing study, including the potential utility of human leukocyte antigens and microRNAs as DILI risk factors and new data on racial differences, the role of alcohol consumption, factors associated with prognosis, and updates on the clinical signatures of autoimmune DILI, thiopurines, and HDS agents. Novel data were also generated from the Spanish and Latin American DILI registries as well as from Chinese and Korean case series. A few new agents causing DILI were added to the growing list in the past 2 years, including sodium-glucose co-transporter-2 inhibitors, as were new aspects of chemotherapy-associated liver injury. A number of cases reported previously described hepatotoxins confirmed via the Roussel Uclaf Causality Assessment Method (RUCAM; e.g., norethisterone, methylprednisolone, glatiramer acetate) and/or the DILIN method (e.g., celecoxib, dimethyl fumarate). Additionally, much work centered on elucidating the pathophysiology of DILI, including the importance of bile salt export pumps and immune-mediated mechanisms. Finally, it must be noted that, while hundreds of new studies described DILI in 2017-2018, the quality of such reports must always be addressed. Björnsson reminds us to remain very critical of the data when addressing the future utility of a study, which is why it is so important to adhere to a standardized method such as RUCAM when determining DILI causality. While drug-induced hepatotoxicity remains a diagnosis of exclusion, the diverse array of publications that appeared in 2017 and 2018 provided important advances in our understanding of DILI, paving the way for our improved ability to make a more definitive diagnosis and risk assessment.
药物性肝损伤（DILI）、草药诱导的肝损伤以及草药和膳食补充剂（HDS）诱导的肝损伤是药物安全性的一个重要方面。在过去的一年中，人们对导致肝损伤的药物、机制、风险因素以及检测肝损伤的诊断工具的了解不断增加。本综述重点介绍了我们认为 2017 年和 2018 年与药物、草药产品和膳食补充剂相关的肝损伤相关的 1800 多篇文章中最重要的出版物。美国药物性肝损伤网络（DILIN）前瞻性研究强调了正在进行的研究领域，包括人类白细胞抗原和 microRNAs 作为 DILI 风险因素的潜在用途，以及种族差异、酒精消费的作用、与预后相关的因素和自身免疫性 DILI、硫唑嘌呤和 HDS 制剂的临床特征的最新数据。来自西班牙和拉丁美洲 DILI 登记处以及中国和韩国病例系列的新数据也被生成。在过去的 2 年中，一些新的导致 DILI 的药物被添加到不断增长的清单中，包括钠-葡萄糖共转运蛋白-2 抑制剂，以及化疗相关肝损伤的新方面。一些先前报道的描述性肝毒素通过 Roussel Uclaf 因果关系评估方法（RUCAM；例如，炔诺酮、甲基强的松龙、醋酸格拉替雷）和/或 DILIN 方法（例如，塞来昔布、二甲基富马酸）得到证实。此外，许多工作集中在阐明 DILI 的病理生理学，包括胆汁盐输出泵和免疫介导机制的重要性。最后，必须指出的是，尽管 2017-2018 年有数百项新研究描述了 DILI，但必须始终解决此类报告的质量问题。Björnsson 提醒我们，在解决研究的未来用途时，对数据要持非常批判的态度，这就是为什么在确定 DILI 因果关系时采用 RUCAM 等标准化方法非常重要。虽然药物性肝毒性仍然是一种排除性诊断，但 2017 年和 2018 年发表的多样化的出版物在我们对 DILI 的理解方面取得了重要进展，为我们提高更明确诊断和风险评估的能力铺平了道路。
