Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease
Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease.
(1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease.
We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC–MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease.
Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality.
Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.
KeywordsAA EPA DHA PUFA Lipid mediator Metabolomics
Body mass index
Controlled attenuation parameter
International normalized ratio
Model for end-stage liver disease
Sodium model for end-stage liver disease
Partial least squares discriminant analysis
Variable importance in projection
Multiple reaction monitoring
This study was supported in part by NIH Grants R01 AA020703, R01 AA24726, U01 AA021856, U01 AA026939 and by Award Number BX004594 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (to B.S.), and by Fond National de Recherche Scientifique (FNRS) Belgium grants CDR J.0146.17 and PDR T.0217.18 (to P.S.).
B.G. was responsible for data acquisition, analysis, interpretation, and writing of the manuscript; S.L. was responsible for data analysis; Y.D. and Y.W. were responsible for preparation of human samples; D.L.S., A.L., P.M., S.B.H., and P.S. enrolled subjects for bio-specimen collection; and B.S. was responsible for the study concept and design, editing the manuscript, and study supervision.
Compliance with Ethical Standards
Conflict of interest
B.S. is consulting for Ferring Research Institute.