Clinical Application Value of Ceramide and Sphingomyelin as Biomarkers for the Diagnosis of Drug-Induced Liver Injury

Background : Drug-induced liver injury (DILI) is a serious health concern that presents challenges in early detection and accurate diagnosis, thereby complicating the treatment of this liver disease. Therefore, it is crucial to explore specific biomarkers to improve the accuracy of diagnosing DILI.
Methods : A study was conducted involving patients with DILI, non-drug-related benign liver diseases (NDILI), and healthy controls (HCs). Serum metabolomic profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS), and transcriptomic data were retrieved from public datasets for integrated analysis. Biomarkers and cytokines were detected using enzyme-linked immunosorbent assays (ELISA). Differential metabolites were identified through multi-omics joint analysis, large sample validation, and logistic regression models.
Results: Transcriptomic analyses highlighted that inflammatory and metabolic pathways are critical to 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, levels of IL-6 and IL-8 were significantly elevated in DILI patients compared to HCs.
Conclusion: This study preliminarily determined that ceramides and sphingolipids are significantly elevated in DILI compared to NDILI and HCs. Their combination with traditional liver function indicators further improves the diagnostic accuracy of DILI. Therefore, ceramides and sphingolipids may serve as potential biomarkers for the diagnosis and management of DILI.