{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:16:54Z","timestamp":1784042214331,"version":"3.55.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"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":[[2021,4]]},"abstract":"<jats:p>Identifying patients at higher risk for poor outcomes from nonalcoholic fatty liver disease (NAFLD) remains challenging. Metabolomics, the comprehensive measurement of small molecules in biological samples, has the potential to reveal novel noninvasive biomarkers. The aim of this study was to determine if serum metabolite profiles in patients with NAFLD associate with future liver\u2010related events. We performed a retrospective single\u2010center cohort study of 187 participants with biopsy\u2010proven NAFLD. Metabolomic analysis was performed on serum using ultrahigh performance liquid chromatography\/tandem mass spectrometry and gas chromatography\/mass spectrometry. We identified liver\u2010related events (variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary or hepatorenal syndrome) by manual chart review between index biopsy (2007\u20102013) and April 1, 2018. Generalized linear models and Cox proportional hazards models were used to test the association of metabolites with liver\u2010related events and time to first liver\u2010related event, controlling for covariates and fibrosis stage. Over a mean\u00a0\u00b1\u00a0SD follow\u2010up of 6.9\u00a0\u00b1\u00a03.2\u00a0years, 11 participants experienced 22 liver\u2010related events. Generalized linear models revealed 53 metabolites significantly associated with liver\u2010related events (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.05). In Cox proportional hazards modeling, 69 metabolites were significantly associated with time to future liver\u2010related events (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.05), seven of which met the false discovery rate threshold of 0.10: vitamin E metabolites gamma\u2010carboxyethyl\u2010hydroxychroman (gamma\u2010CEHC) and gamma\u2010CEHC glucuronide; primary bile acid metabolite taurochenodeoxycholate; serotonin metabolite 5\u2010hydroxyindoleacetate; and lipid metabolites (i) 2\u2010hydroxyglutarate, (ii) 3beta,17beta\u2010diol disulfate 1, and (iii) eicosenoyl sphingomyelin. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Metabolites of a primary bile acid, vitamin E, and serotonin were associated with future liver\u2010related events. Our results suggest metabolite pathways may be useful for predicting which patients with NAFLD are at higher risk for hepatic decompensation.<\/jats:p>","DOI":"10.1002\/hep4.1665","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T05:30:40Z","timestamp":1609911040000},"page":"608-617","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":27,"title":["Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver\u2010Related Events in Nonalcoholic Fatty Liver Disease"],"prefix":"10.1097","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1024-9040","authenticated-orcid":false,"given":"Kara","family":"Wegermann","sequence":"first","affiliation":[{"name":"Division of Gastroenterology,Department of Medicine,Duke University Hospital,Durham,NC,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Howe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Department of Medicine,Vanderbilt University Medical Center,Nashville,TN,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Henao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics,Duke University,Durham,NC,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Department of Medicine,Duke University Hospital,Durham,NC,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia D.","family":"Guy","sequence":"additional","affiliation":[{"name":"Department of Pathology,Duke University Hospital,Durham,NC,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal F.","family":"Abdelmalek","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Department of Medicine,Duke University Hospital,Durham,NC,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Mae","family":"Diehl","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Department of Medicine,Duke University Hospital,Durham,NC,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8454-7086","authenticated-orcid":false,"given":"Cynthia A.","family":"Moylan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Department of Medicine,Duke University Hospital,Durham,NC,USA"},{"name":"Department of Medicine,Durham Veterans Affairs Medical 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