{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T18:09:54Z","timestamp":1772302194872,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["K23AA029198\u201001"],"award-info":[{"award-number":["K23AA029198\u201001"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol\u2010associated liver disease (ALD). Early\u2010stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut\u2010barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010nine male and female AUD patients were grouped by normal [\u226571\u2009<jats:italic>\u03bc<\/jats:italic>g\/dL (Group 1, number (<jats:italic>n<\/jats:italic>)\u2009=\u200926)] and low [&lt;71\u2009<jats:italic>\u03bc<\/jats:italic>g\/dL (Group 2, <jats:italic>n<\/jats:italic>\u2009=\u200913)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90\u2010days (HDD90), total drinks in the past 90\u2010days (TD90), number of drinking days in the past 90\u2010days (NDD90), average drinks per day in the past 90\u2009days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut\u2010barrier dysfunction markers, cytokines, and hepatocyte death markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Group 2 females exhibited lower LTDH than Group 2 males (<jats:italic>p<\/jats:italic>\u2009=\u20090.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (<jats:italic>p<\/jats:italic>\u2009=\u20090.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL\u20108) levels than Group 1 (<jats:italic>p<\/jats:italic> = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well\u2010described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF\u2010\u03b1) (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.633, <jats:italic>p<\/jats:italic>\u2009=\u20090.037).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrated the role of the gut\u2010immune\u2010liver axis in describing hepatocyte injury and death in zinc\u2010deficient AUD patients. These patients represented an arrangement of gut\u2010barrier dysfunction and an exacerbated immune response. Shift in the cell\u2010death mechanism from apoptosis in zinc\u2010replete females to necrosis in zinc\u2010deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15408","type":"journal-article","created":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T02:23:46Z","timestamp":1722651826000},"page":"1740-1752","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The gut\u2010immune\u2010liver axis in patients with alcohol use disorder and clinically low serum zinc levels"],"prefix":"10.1111","volume":"48","author":[{"given":"Aishwarya","family":"Thakurdesai","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Clinical Laboratory for the Intervention Development of AUD and Organ\u2010Severity University of Louisville  Louisville Kentucky 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