Maris Bianca Raluca, Grama Alina, Pop Tudor Lucian
2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania.
Int J Mol Sci. 2025 Feb 25;26(5):2006. doi: 10.3390/ijms26052006.
Drug-induced liver injury (DILI) is one of the main causes of acute liver failure in children. Its incidence is probably underestimated, as specific diagnostic tools are currently lacking. Over 1000 known drugs cause DILI, and the list is expanding. The aim of this review is to describe DILI pathogenesis and emphasize the drugs accountable for child DILI in order to aid its recognition. Intrinsic DILI is well described in terms of mechanism, incriminated drugs, and toxic dose. Conversely, idiosyncratic DILI (iDILI) is unpredictable, occurring as a result of a particular response to drug administration, and its occurrence cannot be foreseen in clinical studies. Half of pediatric iDILI cases are linked to antibiotics, mostly amoxicillin-clavulanate, in the immune-allergic group, while autoimmune DILI is the hallmark of minocycline and nitrofurantoin. Secondly, antiepileptics are responsible for 20% of pediatric iDILI cases, children being more prone to iDILI caused by these agents than adults. A similar tendency was observed in anti-tuberculosis drugs, higher incidences being reported in children below three years old. Current data show growing cases of iDILI related to antineoplastic agents, atomoxetine, and albendazole, so that it is advisable for clinicians to maintain a high index of suspicion regarding iDILI.
药物性肝损伤(DILI)是儿童急性肝衰竭的主要原因之一。由于目前缺乏特异性诊断工具,其发病率可能被低估。已知有1000多种药物可导致DILI,且这一清单还在不断增加。本综述的目的是描述DILI的发病机制,并强调导致儿童DILI的药物,以帮助识别该病。内在性DILI在机制、涉事药物和中毒剂量方面已有充分描述。相反,特异质性DILI(iDILI)不可预测,是药物给药后特殊反应的结果,其发生在临床研究中无法预见。在免疫过敏组中,一半的儿童iDILI病例与抗生素有关,主要是阿莫西林-克拉维酸,而自身免疫性DILI是米诺环素和呋喃妥因的特征。其次,抗癫痫药物占儿童iDILI病例的20%,儿童比成人更容易发生由这些药物引起的iDILI。在抗结核药物中也观察到类似趋势,3岁以下儿童的发病率更高。目前的数据显示,与抗肿瘤药物、托莫西汀和阿苯达唑相关的iDILI病例不断增加,因此临床医生对iDILI保持高度怀疑是明智的。