Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM
Metadatos
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Andújar Vera, Francisco Luis; Alés Palmer, María Luisa; Muñoz de Rueda, Paloma; Iglesias Baena, Iván; Ocete Hita, EstherMateria
Children DILI Metabolomics Bile acids Liver injury
Fecha
2023-09-01Referencia bibliográfica
Andújar-Vera, F.; Alés-Palmer, M.L.; Muñoz-de- Rueda, P.; Iglesias-Baena, I.; Ocete-Hita, E. Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM. Int. J. Mol. Sci. 2023, 24, 13562. [https://doi.org/10.3390/ijms241713562]
Patrocinador
Institute of Health Carlos III grants (PI17/01989) and Servicio Andaluz de Salud (F2-0071-2015)Resumen
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 (p < 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