Metabolomic screening for diagnostic biomarkers of drug-induced chronic liver injury related cirrhosis

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC=0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.