{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:07:13Z","timestamp":1788433633004,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016970","name":"Ministry of Economy, Knowledge, Business and University, Andalusia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016970","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL\/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52\u2009weeks. The hepatic origin of MVs was addressed using AlbCrexmT\/mG mice fed a Western (WD) or Dual diet for 23\u2009weeks. Besides, we assessed plasma MVs in 130 biopsy\u2010proven NAFLD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT\/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy\u2010proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4\u2009\u00b1\u200961.9 vs 758.4\u2009\u00b1\u200982.3; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Patients with ballooning 367\u2009\u00b1\u200940.6 vs 532.0\u2009\u00b1\u200945.1; <jats:italic>p<\/jats:italic>\u2009=\u20090.01 and lobular inflammation (321.1\u2009\u00b1\u200974.1 vs 721.4\u2009\u00b1\u200980.1; <jats:italic>p<\/jats:italic>\u2009=\u20090.001), showed higher levels of these EVs. These findings were replicated in an independent cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non\u2010invasive biomarker for the evaluation and management of these patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15604","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T10:30:46Z","timestamp":1686220246000},"page":"1909-1919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Role of <scp>EpCAM<\/scp>+ <scp>CD133<\/scp>+ extracellular vesicles in steatosis to steatohepatitis transition in <scp>NAFLD<\/scp>"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-6276","authenticated-orcid":false,"given":"Roc\u00edo","family":"Mu\u00f1oz\u2010Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"SeLiver Group Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD)  Madrid Spain"},{"name":"Departamento de Medicina, Facultad de Medicina Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Gato","sequence":"additional","affiliation":[{"name":"SeLiver Group Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades 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