{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T23:58:53Z","timestamp":1785196733905,"version":"3.55.0"},"reference-count":67,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Heavy alcohol consumption disrupts gut epithelial integrity, leading to increased permeability of the gastrointestinal tract and subsequent translocation of microbes. Regenerating islet\u2010derived protein 3\u03b1 (REG3\u03b1) and Trefoil factor 3 (TFF3) are mainly secreted to the gut lumen by Paneth and Goblet cells, respectively, and are functionally linked to gut barrier integrity. Circulating levels of REG3\u03b1 and TFF3 have been identified as biomarkers for gut damage in several human diseases. We examined whether plasma levels of REG3\u03b1 and TFF3 were dysregulated and correlated with conventional markers of microbial translocation (MT) and pro\u2010inflammatory mediators in heavy drinkers with and without alcoholic hepatitis (AH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cross\u2010sectional and longitudinal studies were performed to monitor plasma levels of REG3\u03b1 and TFF3 in 79 AH patients, 66 heavy drinkers without liver disease (HDC), and 46 healthy controls (HC) at enrollment and at 6\u2010 and 12\u2010month follow\u2010ups. Spearman correlation was used to measure the relationships of REG3\u03b1 and TFF3 levels with MT, disease severity, inflammation, and effects of abstinence from alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At enrollment, AH patients had significantly higher levels of REG3\u03b1 and TFF3 than HDC and HC. The elevated REG3\u03b1 levels were positively correlated with the 30\u2010day fatality rate. Plasma levels of REG3\u03b1 and TFF3 in AH patients differentially correlated with conventional MT markers (sCD14, sCD163, and LBP) and several highly up\u2010regulated inflammatory cytokines\/chemokines\/growth factors. At follow\u2010ups, although REG3\u03b1 and TFF3 levels were decreased in AH patients with alcohol abstinence, they did not fully return to baseline levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Circulating levels of REG3\u03b1 and TFF3 were highly elevated in AH patients and differentially correlated with AH disease severity, MT, and inflammation, thereby serving as potential biomarkers of MT and gut epithelial damage in AH patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14579","type":"journal-article","created":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T17:00:39Z","timestamp":1613408439000},"page":"720-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Blood Biomarkers of Intestinal Epithelium Damage Regenerating Islet\u2010derived Protein 3\u03b1 and Trefoil Factor 3 Are Persistently Elevated in Patients with Alcoholic Hepatitis"],"prefix":"10.1111","volume":"45","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"School of Laboratory Medicine and Life Sciences Wenzhou Medical University Wenzhou Zhejiang China"},{"name":"Department of Microbiology and Immunology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahim","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Life Sciences Wenzhou Medical University Wenzhou Zhejiang China"},{"name":"Department of Microbiology and Immunology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Clinical Laboratory the Second Affiliated 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