Metabolic signatures of hepatolithiasis using ultra-high performance liquid chromatography-tandem mass spectrometry.

BACKGROUND & AIMS: A metabolomic study of hepatolithiasis has yet to be performed. The purpose of the present study was to characterize the metabolite profile and identify potential biomarkers of hepatolithiasis using a metabolomic approach.

METHODS

We comprehensively analyzed the serum metabolites from 30 patients with hepatolithiasis and 20 healthy individuals using ultra-high performance liquid chromatography-tandem mass spectrometry operated in negative and positive ionization modes. Statistical analyses were performed using univariate (Student's t-test) and multivariate (orthogonal partial least-squares discriminant analysis) statistics and R language. Receiver operator characteristic (ROC) curve analysis was performed to identify potential predictors of hepatolithiasis.

RESULTS

We identified 277 metabolites that were significantly different between hepatolithiasis serum group and healthy control serum group. These metabolites were principally lipids and lipid-like molecules and amino acid metabolites. The steroid hormone biosynthesis pathway was enriched in hepatolithiasis serum group. In all specific metabolites, 75 metabolites were over-expressed in hepatolithiasis serum group. The AUC values for 60 metabolites exceeded 0.70, 4 metabolites including 18-β-Glycyrrhetinic acid, FMH, Rifampicin and PC (4:0/16:2) exceeded 0.90.

CONCLUSIONS

We have identified serum metabolites that are associated with hepatolithiasis for the first time. 60 potential metabolic biomarkers were identified, 18-β-Glycyrrhetinic acid, FMH, Rifampicin and PC (4:0/16:2) may have the potential clinical utility in hepatolithiasis.