{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:22Z","timestamp":1785428062596,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of the University","award":["P20222CB2B"],"award-info":[{"award-number":["P20222CB2B"]}]},{"name":"Sapienza University"},{"id":[{"id":"https:\/\/ror.org\/02be6w209","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increased intestinal permeability has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), but its relationship with liver fibrosis independent of metabolic risk factors remains unclear. The aim of this study was to investigate the relationship between markers of gut-derived immune activation and liver fibrosis in individuals with metabolic disease. We enrolled 139 adults (48.8 \u00b1 11 years; BMI 33.7 \u00b1 9.5 kg\/m2; 50% type 2 diabetes); liver steatosis and fibrosis were estimated using the Hepatic Steatosis Index (HSI) and Fibrotic NASH Index (FNI); liver biopsies were available in a bariatric subgroup. Plasma soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP) levels were measured by ELISA kits, and the LBP\/sCD14 ratio was calculated. MASLD was present in 78% of participants; in these individuals, sCD14 levels correlated with HSI and FNI (both p &lt; 0.01). In multivariable analysis adjusting for age, sex, BMI, waist circumference, and type 2 diabetes, sCD14 was independently associated with advanced fibrosis (OR: 3.16, 95% CI 1.32\u20137.55; p = 0.010). This association was confirmed by histology (p = 0.02). Overall, these findings point to a link between gut-derived immune activation and fibrotic burden in MASLD and provide insight into the pathophysiological relevance of the gut\u2013liver axis in metabolic disease.<\/jats:p>","DOI":"10.3390\/ijms27073050","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:32:47Z","timestamp":1774611167000},"page":"3050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Soluble CD14 Levels Predict Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Independently of Obesity and Type 2 Diabetes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0530-8568","authenticated-orcid":false,"given":"Ilaria","family":"Barchetta","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Agata","family":"Cimini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Sentinelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5089-6963","authenticated-orcid":false,"given":"Sara","family":"Dule","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Frattina","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Passarella","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Neve","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7929-7390","authenticated-orcid":false,"given":"Alessandro","family":"Oldani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3224-6078","authenticated-orcid":false,"given":"Marco Giorgio","family":"Baroni","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Neuroendocrinology and Metabolic Diseases, IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-8049","authenticated-orcid":false,"given":"Maria Gisella","family":"Cavallo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/hep.29085","article-title":"Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis","volume":"65","author":"Dulai","year":"2017","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1053\/j.gastro.2020.01.043","article-title":"Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis","volume":"158","author":"Taylor","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: Pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. 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