Metabolomic profiling and biomarkers of drug-induced liver injury with pre-existing alcoholic liver disease

Abstract

With the development of social economy, the problem of drug-induced liver injury (DILI) with pre-existing alcoholic liver disease (ALD) is becoming serious. However, it is often difficult to define the dominant role of ALD combined with DILI (ALD-DILI), and the mechanism of damage pathway is not completely clear. In this paper, metabolomics characterization of samples showed that ALD-DILI was similar to DILI (60 different compounds) rather than ALD (1,232 different compounds) as a whole at the metabolome level. Through metabolite identification and metabolic pathway analysis, it was found that compared with DILI, functional injuries such as bile acid, amino acid and lipid synthesis and decomposition were more serious in ALD-DILI, which is consistent with the clinical results observed by our research group. Furthermore, 4 candidate biomarkers (Phosphatidate, Phosphatidylethanolamine, Taurolithocholate, 3-ketolactose) that can be used to distinguish DILI from ALD-DILI are further screened, and the area under the ROC curve is greater than 0.8. In addition, the ratio of Phosphatidate to 3-ketolactose and taurolithocholate has a better diagnosis effect, and the area under the ROC curve is 0.918 and 0.886, respectively. The ratio method is conducive to reducing the systematic errors of sample processing and detection instruments, and can better assist in the early clinical differential diagnosis of ALD-DILI as well as guide clinical rational drug use.