Digestive Diseases and Sciences

, Volume 64, Issue 7, pp 1878–1892 | Cite as

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease

  • Bei Gao
  • Sonja Lang
  • Yi Duan
  • Yanhan Wang
  • Debbie L. Shawcross
  • Alexandre Louvet
  • Philippe Mathurin
  • Samuel B. Ho
  • Peter Stärkel
  • Bernd SchnablEmail author
Original Article



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.


AA EPA DHA PUFA Lipid mediator Metabolomics 



Alkaline phosphatase


Aspartate aminotransferase


Alanine aminotransferase


Body mass index


Controlled attenuation parameter


International normalized ratio


Model for end-stage liver disease


Sodium model for end-stage liver disease


Polymorphonuclear infiltration


Arachidonic acid


Eicosapentaenoic acid


Docosahexaenoic acid


Hydroperoxyeicosatetraenoic acid


Hydroxyeicosatetraenoic acid


Dihydroxyeicosatetraenoic acid




Thromboxane X


Epoxyeicosatrienoic acid


Dihydroxyeicosatrienoic acid


Hydroperoxy-eicosapentaenoic acid


Hydroxyeicosapentaenoic acid


Dihydroxyeicosapentaenoic acid


Epoxyeicosatetraenoic acid


Hydroperoxydocosahexaenoic acid


Hydroxydocosahexaenoic acid


Dihydroxydocosahexaenoic acid


Dihydroxydocosapentaenoic acid


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.).

Author’s Contribution

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.

Supplementary material

10620_2019_5638_MOESM1_ESM.jpg (165 kb)
Supplemental Figure S1 Venn diagram of significantly altered oxylipins found in both serum and fecal samples (adjusted p value < 0.05). Ctrl: controls; AUD: alcoholic use disorder; AH: alcoholic hepatitis (JPEG 165 kb)
10620_2019_5638_MOESM2_ESM.jpg (268 kb)
Supplemental Figure S2 Spearman correlation of fecal oxylipins with laboratory parameters in alcoholic hepatitis and alcohol use disorder patients. Color intensity represents the correlation coefficient (R). Red: positive correlation. Blue: negative correlation. * p < 0.05, ** p < 0.01, *** p < 0.001. INR, international normalized ratio; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyltransferase; AP, alkaline phosphatase (JPEG 267 kb)
10620_2019_5638_MOESM3_ESM.jpg (487 kb)
Supplemental Figure S3 Spearman correlation of fecal oxylipins with parameters of liver disease stage in alcohol use disorder patients (A). CAP: controlled attenuation parameter. Color intensity represents the correlation coefficient (R). Red: positive correlation. Blue: negative correlation. * p < 0.05. Number of alcohol use disorder patients N = 30. Spearman correlation of fecal oxylipins with liver histology and clinical scores in alcoholic hepatitis patients (B). Color intensity represents the correlation coefficient (R). Red: positive correlation. Blue: negative correlation. * p < 0.05, ** p < 0.01, *** p < 0.001. MELD, model for end-stage liver disease; MELDNa, sodium model for end-stage liver disease. Number of alcoholic hepatitis patients N = 7 (JPEG 486 kb)
10620_2019_5638_MOESM4_ESM.xlsx (17 kb)
Supplementary material 4 (XLSX 17 kb)
10620_2019_5638_MOESM5_ESM.xlsx (11 kb)
Supplementary material 5 (XLSX 11 kb)
10620_2019_5638_MOESM6_ESM.xlsx (22 kb)
Supplementary material 6 (XLSX 22 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Bei Gao
    • 1
  • Sonja Lang
    • 1
  • Yi Duan
    • 1
    • 2
  • Yanhan Wang
    • 1
    • 2
  • Debbie L. Shawcross
    • 3
  • Alexandre Louvet
    • 4
  • Philippe Mathurin
    • 4
  • Samuel B. Ho
    • 1
    • 2
  • Peter Stärkel
    • 5
  • Bernd Schnabl
    • 1
    • 2
    Email author
  1. 1.Department of MedicineUniversity of California San DiegoLa JollaUSA
  2. 2.Department of MedicineVA San Diego Healthcare SystemSan DiegoUSA
  3. 3.Institute of Liver Studies, King’s College London School of Medicine at King’s College HospitalKing’s College HospitalLondonUK
  4. 4.Service des Maladies de L’appareil Digestif et Unité INSERMHôpital HuriezLilleFrance
  5. 5.St. Luc University HospitalUniversité Catholique de LouvainBrusselsBelgium

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