J Clin Exp Hepatol. 2026 Sep-Oct;16(5):103603. doi: 10.1016/j.jceh.2026.103603. Epub 2026 Jul 1.
ABSTRACT
BACKGROUND/AIMS: Drug-induced liver injury (DILI) is a serious health concern that presents challenges for early detection and accurate diagnosis, thereby complicating the treatment of this liver disease.
METHODS: This study involved patients with DILI, non-drug-related benign liver diseases (NDILI), and healthy controls (HCs). Serum metabolomic profiles were analyzed using liquid chromatography-mass spectrometry, and transcriptomic data were retrieved from public datasets for integrated analysis. Biomarkers and cytokines were detected using enzyme-linked immunosorbent assays. Differential metabolites were identified through multiomics joint analysis, large sample validation, and logistic regression models.
RESULTS: Transcriptomic analyses highlighted that inflammatory and metabolic pathways play critical roles in DILI pathogenesis. Integrated transcriptomic-metabolomic analysis revealed significant alterations in sphingolipid metabolism, with ceramide and sphingomyelin emerging as key metabolites for distinguishing DILI, NDILI, and HCs. The multivariable diagnostic model combining ceramide, sphingomyelin, and traditional biomarkers demonstrated superior performance. Notably, the levels of IL-6 and IL-8 were significantly elevated in DILI patients compared to HCs.
CONCLUSION: This study preliminarily determined that ceramides are significantly elevated in DILI compared to NDILI and HCs, while sphingomyelin is decreased. Their combination with traditional liver function indicators further improves the diagnostic accuracy of DILI. Therefore, ceramides and sphingomyelin may serve as potential biomarkers for the diagnosis and management of DILI.
PMID:42495512 | PMC:PMC13392872 | DOI:10.1016/j.jceh.2026.103603