Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Malaga, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Nat Rev Dis Primers. 2019 Aug 22;5(1):58. doi: 10.1038/s41572-019-0105-0.
Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredictable event with many drugs in common use. Drugs can be harmful to the liver in susceptible individuals owing to genetic and environmental risk factors. These risk factors modify hepatic metabolism and excretion of the DILI-causative agent leading to cellular stress, cell death, activation of an adaptive immune response and a failure to adapt, with progression to overt liver injury. Idiosyncratic DILI is a relative rare hepatic disorder but can be severe and, in some cases, fatal, presenting with a variety of phenotypes, which mimic other hepatic diseases. The diagnosis of DILI relies on the exclusion of other aetiologies of liver disease as specific biomarkers are still lacking. Clinical scales such as CIOMS/RUCAM can support the diagnostic process but need refinement. A number of clinical variables, validated in prospective cohorts, can be used to predict a more severe DILI outcome. Although no pharmacological therapy has been adequately tested in randomized clinical trials, corticosteroids can be useful, particularly in the emergent form of DILI related to immune-checkpoint inhibitors in patients with cancer.
药物性肝损伤(DILI)是一种对药物或其他外源性物质的不良反应,发生在个体暴露于某些化合物的毒性剂量时,可预测;也可发生在许多常用药物中,不可预测。由于遗传和环境风险因素,药物在易感性个体中可能对肝脏有害。这些风险因素会改变肝脏对 DILI 致病剂的代谢和排泄,导致细胞应激、细胞死亡、适应性免疫反应的激活和无法适应,进而发展为明显的肝损伤。特异质 DILI 是一种相对罕见的肝脏疾病,但可能很严重,在某些情况下是致命的,表现为多种表型,类似于其他肝脏疾病。DILI 的诊断依赖于排除其他肝病的病因,因为目前仍然缺乏特异性生物标志物。CIOMS/RUCAM 等临床量表可以支持诊断过程,但需要进一步改进。一些在前瞻性队列中得到验证的临床变量可用于预测更严重的 DILI 结局。虽然皮质类固醇等药物在随机临床试验中没有得到充分测试,但在癌症患者因免疫检查点抑制剂相关的紧急型 DILI 中可能有用。