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ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis (ASH), with chronic ASH eventually leading to fibrosis, cirrhosis, and, in some cases, hepatocellular carcinoma. The pathogenesis of ALD is driven by hepatic steatosis, oxidative stress, and acetaldehyde toxicity. Alcohol consumption disrupts lipid metabolism by inactivating PPAR\u03b1, exacerbating the progression of ALD. EFN primarily activates PPAR\u03b1, promoting lipolysis and \u03b2-oxidation in ethanol-stimulated HepG2 cells, which significantly reduces hepatic steatosis, apoptosis, and fibrosis in an ALD mouse model. Additionally, alcohol disrupts the gut-liver axis at several interconnected levels, contributing to a proinflammatory environment in the liver. EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy, inhibiting apoptosis and inflammatory responses, and enhancing intestinal barrier function through PPAR\u03b4 activation.<\/jats:p>","DOI":"10.3748\/wjg.v30.i43.4660","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T07:23:36Z","timestamp":1730359416000},"page":"4660-4668","source":"Crossref","is-referenced-by-count":10,"title":["Elafibranor alleviates alcohol-related liver fibrosis by restoring intestinal barrier function"],"prefix":"10.3748","volume":"30","author":[{"given":"Yu-Qi","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Yao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.23736\/S0026-4806.24.09355-8"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.08.009"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0014-7"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2191"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00827.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.003"},{"key":"B7","doi-asserted-by":"crossref","unstructured":"Rao RK. 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