Application of metabolomics in drug-induced liver injury: A systematic review

Drug-induced liver injury (DILI) is one of the most common adverse reactions in clinical settings, and drug hepatotoxicity is also a primary factor contributing to the suspension and withdrawal of drug development. Currently, there are no specific biomarkers available for the early diagnosis and monitoring of DILI in clinical practice. In recent years, metabolomics has emerged as a powerful tool for identifying small molecule biomarkers in DILI, owing to its unique advantages. In this article, we comprehensively reviewed the metabolomics studies related to DILI to investigate the pathophysiological changes in DILI and to assess the potential application of metabolomics in its prediction and diagnosis. Relevant literature published before 30 April 2024 was retrieved from four online databases (PubMed, EMbase, Cochrane Library, and Web of Science). Research data were systematically collected, and the metabolites involved were analyzed. Metabolic pathway analysis related to DILI was conducted using the online software MetaboAnalyst 5.0. A total of 55 studies were included, identifying significantly altered metabolic pathways and valuable metabolic biomarkers. The most frequently reported biomarkers included glycocholic acid, taurochenodeoxycholic acid, taurocholic acid, creatine, glycochenodeoxycholic acid, taurodeoxycholic acid, glycodeoxycholic acid, and α -ketoglutaric acid. The disrupted metabolic pathways were mainly related to bile acid metabolism, lipid metabolism, and the tricarboxylic acid cycle, among which bile acid metabolism showing the most prominent alterations. Lipid metabolism-related pathways included fatty acid biosynthesis, glycerophospholipid metabolism, and sphingolipid metabolism. This article provides a systematic review of metabolomics in DILI, deepening our understanding of the metabolic disturbances caused by DILI.