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This study characterized circulating fibronectin across stages of advanced chronic liver disease (ACLD) and assessed its correlation to pathophysiological biomarkers and predictive value for liver-related complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled with circulating fibronectin measured simultaneously. Associations were assessed using correlation analyses and systems modeling. Competing-risk regression was used to evaluate clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 298 patients (median HVPG 17 [12\u201321] mmHg; MELD 3.0 12 [9\u201317]), fibronectin levels were lower in decompensated than compensated ACLD (30.3 vs. 38.8\u00a0mg\/dL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Fibronectin correlated with hepatic synthesis (cholinesterase: Spearman\u2019s\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.64) and MELD 3.0 (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2212\u00a00.47; both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) while showing an independent positive association with ELF (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.19;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In systems modeling, hepatic synthesis explained most of fibronectin variance (cholinesterase: 37%), followed by fibrinolysis (antiplasmin: 14%) and matrix remodeling (ELF: 12%). In exploratory analyses, higher fibronectin levels were independently associated with variceal bleeding (aSHR 1.04,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017), and lower fibronectin levels with portal vein thrombosis (aSHR 0.95,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031), when adjusted for HVPG, MELD 3.0, or IL-6. Fibronectin was not associated with other hepatic decompensation events, hepatocellular carcinoma, or liver-related mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Circulating fibronectin reflects hepatic synthetic capacity and matrix remodeling. Its divergent exploratory associations with variceal bleeding and portal vein thrombosis suggest that fibronectin may capture aspects of hemostatic vulnerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>NCT03267615.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-026-11140-1","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:16:21Z","timestamp":1790345781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating fibronectin levels are linked to liver function, matrix remodeling, and hemostatic complications in advanced chronic liver disease"],"prefix":"10.1007","clinical-trial-number":[{"clinical-trial-number":"nct03267615","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Georg","family":"Kramer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina Andreea","family":"Lie-Ungurean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt Silvester","family":"Hofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Hartl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Jachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Balcar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Semmler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Sebesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Th\u00f6ne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Hintersteininger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"H\u00f6finger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrig","family":"Marculescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Perkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schwabl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-3583","authenticated-orcid":false,"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"10308","key":"11140_CR1","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1016\/S0140-6736(21)01374-X","volume":"398","author":"P Gin\u00e8s","year":"2021","unstructured":"Gin\u00e8s P, Krag A, Abraldes JG, et al. 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I.L. has nothing to disclose. B.S.H. received travel support from Falk and Ipsen, speaking honoraria from Gilead and honoraria for educational materials from Ipsen. L.H. has nothing to disclose. M.J. served as speaker and\/or consultant for Gilead Sciences Inc. L.B. served as an advisory board member for Boehringer Ingelheim and received travel support from Roche. G.S. received travel support from Amgen and served as a speaker for DiaSorin. C.S. has nothing to disclose. P.T. has nothing to disclose. M.H. received speaking honoraria from Gilead as well as travel support from Gilead and Roche. P.H. has nothing to disclose. R.M. has nothing to disclose. T.P. has nothing to disclose. P.S. received consulting fees from PharmaIN and travel support from Falk Pharma. M.T. received grant support from Albireo, Alnylam, Cymabay, Falk, Genentech, Gilead, Intercept, MSD, Takeda and UltraGenyx, honoraria for consulting from AbbVie, Albireo, Alfasigma, Agomab, Boehringer Ingelheim, BiomX, Chemomab, Dexoligo Therapeutics, Falk, Genfit, Gilead, GSK, Hightide, Intercept, Ipsen, Janssen, Mirum, MSD, Novartis, Phenex, Pliant, ProQR Therapeutics, Regulus, Siemens and Shire, speaker fees from Albireo, Boehringer Ingelheim, Bristol-Myers Squibb, Falk, Gilead, Ipsen, Intercept, Madrigal, Mirum and MSD, as well as travel support from AbbVie, Falk, Gilead, Janssen and Intercept, Ipsen and Janssen. He is also co-inventor of patents on the medical use of 24-norursodeoxycholic acid filed by the Medical University of Graz. M.M. served as a speaker and\/or consultant and\/or advisory board member for AbbVie, Echosens, Eli Lilly, Falk, Gilead, Ipsen, Takeda, and W. L. Gore & Associates; received travel support from AbbVie and Gilead; and received grants\/research support from Echosens. T.R. received grant support from Abbvie, Boehringer Ingelheim, Gilead, Intercept\/Advanz Pharma, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, Siemens, and W. L. Gore & Associates; speaking honoraria from Abbvie, Echosens, Gilead, Intercept\/Advanz Pharma, Roche, MSD, and W. L. Gore & Associates; consulting\/advisory board fees from Abbvie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Intercept\/Advanz Pharma, MSD, Resolution Therapeutics, and Siemens; and travel support from Abbvie, Boehringer Ingelheim, Dr. Falk Pharma, Gilead and Roche. B.Si. received travel support from AbbVie, Gilead, and Falk.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}