Bioinformatic Unit, Biosanitary Research Institute ibs.GRANADA, 18012 Granada, Spain.
Department of Pediatrics, University of Granada, 18016 Granada, Spain.
Int J Mol Sci. 2023 Sep 1;24(17):13562. doi: 10.3390/ijms241713562.
Hepatotoxicity, a common adverse drug effect, has been extensively studied in adult patients. However, it is equally important to investigate this condition in pediatric patients to develop personalized treatment strategies for children. This study aimed to identify plasma biomarkers that characterize hepatotoxicity in pediatric patients through an observational case-control study. Metabolomic analysis was conducted on 55 pediatric patients with xenobiotic liver toxicity and 88 healthy controls. The results revealed clear differences between the two groups. Several metabolites, including hydroxydecanoylcarnitine, octanoylcarnitine, lysophosphatidylcholine, glycocholic acid, and taurocholic acid, were identified as potential biomarkers (area under the curve: 0.817; 95% confidence interval: 0.696-0.913). Pathway analysis indicated involvement of primary bile acid biosynthesis and the metabolism of taurine and hypotaurine ( < 0.05). The findings from untargeted metabolomic analysis demonstrated an increase in bile acids in children with hepatotoxicity. The accumulation of cytotoxic bile acids should be further investigated to elucidate the role of these metabolites in drug-induced liver injury.
肝毒性是一种常见的药物不良反应，已在成年患者中进行了广泛研究。然而，同样重要的是要在儿科患者中研究这种情况，以便为儿童制定个性化的治疗策略。本研究旨在通过观察性病例对照研究，确定能够表征儿科患者肝毒性的血浆生物标志物。对 55 名具有外源性肝毒性的儿科患者和 88 名健康对照者进行了代谢组学分析。结果显示两组之间存在明显差异。几种代谢物，包括羟基癸酰肉碱、辛酰肉碱、溶血磷脂酰胆碱、甘胆酸和牛磺胆酸，被鉴定为潜在的生物标志物（曲线下面积：0.817；95%置信区间：0.696-0.913）。途径分析表明原发性胆汁酸生物合成和牛磺酸及次牛磺酸代谢参与其中（<0.05）。非靶向代谢组学分析的结果表明，肝毒性儿童的胆汁酸水平升高。应进一步研究细胞毒性胆汁酸的积累，以阐明这些代谢物在药物性肝损伤中的作用。
