{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:54:31Z","timestamp":1790103271697,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,4,5]],"date-time":"2014-04-05T00:00:00Z","timestamp":1396656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"\u2018Alberto Sordi\u2019 Foundation, Rome, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Notwithstanding evidences implicating the lipopolysaccharides (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>)\/toll\u2010like receptor\u20104 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4) axis in the pathogenesis of <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>, there are no studies aimed to characterize hepatic <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 expression in <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> patients. We aimed to analyse hepatic <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 expression and to verify its relationship with disease activity\/evolution in <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver tissue from 74 patients with <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> and 12 controls was analysed by immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) for <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4, \u03b1\u2013smooth muscle actin (\u03b1\u2013<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) and cytokeratin\u20107. <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> for \u03b1\u2013<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> was used to evaluate activation of fibrogenic cells (hepatic stellate cells and portal\/septal myofibroblasts), that for cytokeratin\u20107 to count hepatic progenitor cells and bile ducts\/ductules, and that for <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>68, in a subgroup of 27 patients, for detecting macrophages. Serum <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010binding protein (<jats:styled-content style=\"fixed-case\">LBP<\/jats:styled-content>), a sensitive marker of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> activity, was determined in 36 patients and 32 controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As confirmed by double\u2010labelling experiments, the highest level of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 expression was observed in hepatic progenitor cells, biliary cells and portal\/septal macrophages. <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010positive hepatic progenitor cells and bile ducts\/ductules correlated with portal\/interface inflammation, activity of fibrogenic cells and fibrosis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Also the score of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 positivity of porto\u2010septal inflammatory infiltrate correlated with number of hepatic progenitor cells and bile ducts\/ductules, activity of fibrogenic cells and fibrosis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Serum <jats:styled-content style=\"fixed-case\">LBP<\/jats:styled-content> was increased in patients compared to controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and correlated with portal\/interface inflammation, activity of portal\/septal myofibroblasts and fibrosis (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 expression by regenerating and inflammatory cells at the porto\u2010septal and interface level, favoured by increased <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> activity, is associated with activation of fibrogenic cells and the degree of fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12531","type":"journal-article","created":{"date-parts":[[2014,3,20]],"date-time":"2014-03-20T19:01:35Z","timestamp":1395342095000},"page":"569-581","source":"Crossref","is-referenced-by-count":91,"title":["Hepatic toll\u2010like receptor 4 expression is associated with portal inflammation and fibrosis in patients with <scp>NAFLD<\/scp>"],"prefix":"10.1111","volume":"35","author":[{"given":"Umberto","family":"Vespasiani\u2010Gentilucci","sequence":"first","affiliation":[{"name":"Clinical Medicine and Hepatology Unit University Campus Bio\u2010Medico of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Carotti","sequence":"additional","affiliation":[{"name":"Laboratory of Microscopic and Ultrastructural Anatomy CIR University Campus Bio\u2010Medico of Rome Rome 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