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 Schnabl
Author Information
Bei Gao: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Sonja Lang: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Yi Duan: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Yanhan Wang: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Debbie L Shawcross: Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, King's College Hospital, London, UK.
Alexandre Louvet: Service des Maladies de L'appareil Digestif et Unité INSERM, Hôpital Huriez, Lille, France.
Philippe Mathurin: Service des Maladies de L'appareil Digestif et Unité INSERM, Hôpital Huriez, Lille, France.
Samuel B Ho: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Peter Stärkel: St. Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium.
Bernd Schnabl: Department of Medicine, University of California San Diego, La Jolla, CA, USA. beschnabl@ucsd.edu.
BACKGROUND: 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. AIMS: (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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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