{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:38:56Z","timestamp":1791722336612,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, often progressing to fibrosis and up to cirrhosis. Platelet activation plays a potential role in MASLD progression, but its functional profile across disease stages remains unclear. This study aimed to characterise the platelet functional profile and phenotype in patients with MASLD \u2264\u2009F2 and F3\u2013F4 fibrosis compared to healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed biomarkers of in\u00a0vivo platelet activation, including urinary 11\u2010dehydro\u2010thromboxane B2 (11\u2010dh\u2010TXB\n                      <jats:sub>2<\/jats:sub>\n                      ) and plasma soluble P\u2010selectin. Platelet phenotype was assessed via microfluidic assays and flow cytometry, evaluating adhesion and fibrinogen receptor activation and Annexin V. Patients were stratified according to liver stiffness measurement (LSM) into low fibrosis MASLD (\u2264\u2009F2) and advanced fibrosis\/cirrhosis (F3\u2013F4).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Urinary 11\u2010dh\u2010TXB\n                      <jats:sub>2<\/jats:sub>\n                      was comparable between control and the \u2264\u2009F2 patients (median difference: 7365\u2009ng\/g creatinine, 95% CI: 5257\u20138764); higher values were observed in F3\u2013F4 patients, with levels significantly elevated compared to controls (6931\u2009ng\/g creatinine, 95% CI: 5290\u20138363). Plasma soluble P\u2010selectin followed a similar trend. Platelet phenotype MASLD \u2264\u2009F2 patients exhibited increased adhesiveness (median difference: 289.8\u2009a.u., 95% CI: 195.8\u2013458.2) and displayed procoagulant activity through binding of Annexin V, whereas F3\u2013F4 patients showed increased adhesiveness (median difference: 361.1\u2009a.u., 95% CI: 163.4\u2013530.4) and reduced fibrinogen receptor activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Platelet activation markers correlate with fibrosis severity, highlighting their potential role in disease progression. MASLD \u2264\u2009F2 is associated with increased platelet adhesiveness, whereas F3\u2013F4 is characterised by impaired platelet reactivity despite high activation markers. These findings support the involvement of platelets in MASLD fibrosis progression and suggest their potential as biomarkers or therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact and Implications<\/jats:title>\n                    <jats:p>This study provides a robust scientific rationale for further exploring platelet dynamics as both biomarkers and potential therapeutic targets in MASLD, by demonstrating distinct platelet functional profiles between early (MASLD \u2264\u2009F2) and advanced fibrosis (F3\u2013F4). The observed increase in platelet adhesiveness and procoagulant activity in early MASLD, contrasted with a reduced reactivity in advanced stages despite elevated activation markers, is critical for clinicians and researchers aiming to refine risk stratification and optimise treatment strategies. These findings could be practically applied by guiding physicians in monitoring platelet activation markers to identify patients at higher risk of fibrosis progression and by informing the development of targeted antiplatelet interventions. However, given the cross\u2010sectional design of the study and its inherent methodological limitations, these implications warrant cautious interpretation and further validation through longitudinal research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>1612CESC<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70231","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T13:09:04Z","timestamp":1753708144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Platelet Functional Profile Is Altered in Metabolic Dysfunction\u2010Associated Steatotic Liver Disease"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7542-601X","authenticated-orcid":false,"given":"Marco","family":"Castelli","sequence":"first","affiliation":[{"name":"Department of Medicine, Medicine C University of Verona and Hospital Trust of Verona (Azienda Ospedaliera Universtaria AOUI)  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Zoncap\u00e8","sequence":"additional","affiliation":[{"name":"Liver Unit, Department Medicine University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Meneguzzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medicine C University of Verona and Hospital Trust of Verona (Azienda Ospedaliera Universtaria AOUI)  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medicine C University of Verona and Hospital Trust of Verona (Azienda Ospedaliera Universtaria AOUI)  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sacerdoti","sequence":"additional","affiliation":[{"name":"Liver Unit, Department Medicine University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Minuz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medicine C University of Verona and Hospital Trust of Verona (Azienda Ospedaliera Universtaria AOUI)  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0402-4176","authenticated-orcid":false,"given":"Andrea","family":"Dalbeni","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medicine C University of Verona and Hospital Trust of Verona (Azienda Ospedaliera Universtaria AOUI)  Verona 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