{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:14:56Z","timestamp":1789866896619,"version":"4.0.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>Alcohol\u2010associated liver disease (ALD) is a spectrum of liver disorders ranging from steatosis to steatohepatitis, fibrosis, and cirrhosis. Alcohol\u2010associated hepatitis (AH) is an acute and often severe form of ALD with substantial morbidity and mortality. The mechanisms and mediators of ALD progression and severity are not well understood, and effective therapeutic options are limited. Various bioactive lipid mediators have recently emerged as important factors in ALD pathogenesis. The current study aimed to examine alterations in linoleic acid (LA)\u2010derived lipid metabolites in the plasma of individuals who are heavy drinkers and to evaluate associations between these molecules and markers of liver injury and systemic inflammation. Analysis of plasma LA\u2010derived metabolites was performed on 66 individuals who were heavy drinkers and 29 socially drinking but otherwise healthy volunteers. Based on plasma alanine aminotransferase (ALT) levels, 15 patients had no liver injury (ALT\u00a0\u2264\u00a040\u00a0U\/L), 33 patients had mild liver injury (ALT\u00a0&gt;\u00a040\u00a0U\/L), and 18 were diagnosed with moderate AH (mAH) (Model for End\u2010Stage Liver Disease score\u00a0&lt;20). Lipoxygenase\u2010derived LA metabolites (13\u2010hydroxy\u2010octadecadienoic acid [13\u2010HODE] and 13\u2010oxo\u2010octadecadienoic acid) were markedly elevated only in patients with mAH. The cytochrome P450\u2010derived LA epoxides 9,10\u2010epoxy\u2010octadecenoic acid (9,10\u2010EpOME) and 12,13\u2010EpOME were decreased in all patients regardless of the presence or absence of liver injury. LA\u2010derived diols 9,10\u2010dihydroxy\u2010octadecenoic acid (9,10\u2010DiHOME) and 12,13\u2010DiHOME as well as the corresponding diol\/epoxide ratio were elevated in the mAH group, specifically compared to patients with mild liver injury. We found that 13\u2010HODE and 12,13\u2010EpOME (elevated and decreased, respectively) in combination with elevated interleukin\u20101\u03b2 as independent predictors can effectively predict altered liver function as defined by elevated bilirubin levels. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Specific changes in LA metabolites in individuals who are heavy drinkers can distinguish individuals with mAH from those with mild ALD.<\/jats:p>","DOI":"10.1002\/hep4.1686","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T23:34:10Z","timestamp":1613000050000},"page":"947-960","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":25,"title":["Linoleic Acid\u2010Derived Oxylipins Differentiate Early Stage Alcoholic Hepatitis From Mild Alcohol\u2010Associated Liver Injury"],"prefix":"10.1097","volume":"5","author":[{"given":"Dennis","family":"Warner","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,University of Louisville,Louisville,KY,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vatsalya","family":"Vatsalya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,University of Louisville,Louisville,KY,USA"},{"name":"Robley Rex Veterans Medical Center,Louisville,KY,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara H.","family":"Zirnheld","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,University of Louisville,Louisville,KY,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Warner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,University of Louisville,Louisville,KY,USA"},{"name":"Department of Pharmacology and Toxicology,University of Louisville School of Medicine,KY,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiah E.","family":"Hardesty","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,University of Louisville,Louisville,KY,USA"},{"name":"Department of Pharmacology and Toxicology,University of Louisville School of Medicine,KY,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Umhau","sequence":"additional","affiliation":[{"name":"Alcohol Recovery Medicine,Potomac,MD,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"McClain","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,University of Louisville,Louisville,KY,USA"},{"name":"Robley Rex Veterans Medical Center,Louisville,KY,USA"},{"name":"Department of Pharmacology and Toxicology,University of Louisville School of Medicine,KY,USA"},{"name":"University of Louisville Alcohol Center,Louisville,KY,USA"},{"name":"Hepatobiology and Toxicology Center,University of Louisville School of Medicine,Louisville,KY,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnarao","family":"Maddipati","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine,Detroit,MI,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-6451","authenticated-orcid":false,"given":"Irina A.","family":"Kirpich","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Medicine,University of Louisville,Louisville,KY,USA"},{"name":"Department of Pharmacology and Toxicology,University of Louisville 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