{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:29:05Z","timestamp":1792459745099,"version":"4.5.0"},"reference-count":16,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Porto\u2010sinusoidal vascular disorder (PSVD) is characterised by lesions involving portal veins and sinusoids in absence of cirrhosis with an unclear pathophysiology. However, its association with immunodeficiency, bowel disorders and abdominal bacterial infections supports the role of altered intestinal permeability and gut\u2010derived endotoxins. The study aimed at assessing the association between serological markers of increased intestinal permeability, pro\u2010aggregating\/procoagulant state and liver injury in PSVD and portal hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010three patients with biopsy\u2010proven PSVD and portal hypertension and 33 healthy subjects were submitted to a venous blood sampling for the measurement of zonulin and lipopolysaccharides (LPS) as markers of intestinal permeability, of s\u2010Glycoprotein VI, sP\u2010selectin, ADAMTS13 and von Willebrand factor (vWF), as markers of platelet aggregation and microvascular inflammation, factor VIII and F1\u2009+\u20092 as markers of hypercoagulability. In 17 PSVD patients, histomorphological and immunohistochemical study on liver biopsies was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with controls, PSVD patients had higher levels of LPS, zonulin, vWF, factor VIII and sP\u2010selectin, F1\u2009+\u20092. ADAMTS13 was reduced. Serum LPS correlated with zonulin, sP\u2010selectin, FVIII and vWF. At histological analysis, PSVD specimens had increased LPS localisation, toll\u2010like receptor\u20104(TLR4)\u2010positive macrophages and platelet number compared with samples from healthy liver donors. TLR4+ macrophage number correlated with portal inflammation and fibrosis. Sinusoid dilation and capillarisation were observed. PSVD biopsies showed signs of biliary damage and reduced ductular reaction without alteration in Sox9+ cell population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PSVD patients display an altered intestinal permeability and endotoxemia correlated to a pro\u2010aggregating\/procoagulant state; histologically, PSVD was associated with increased TLR4+ cell involvement and platelet clumps within sinusoids. Our study suggests that LPS\u2010TLR4 pathway could contribute to the pathophysiological basis of PSVD with portal hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17727","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T09:04:04Z","timestamp":1695200644000},"page":"1205-1216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Association between gut\u2010derived endotoxins and porto\u2010sinusoidal vascular disorder with portal hypertension"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3940-4390","authenticated-orcid":false,"given":"Stefania","family":"Gioia","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Carnevale","sequence":"additional","affiliation":[{"name":"Department of Medical\u2010Surgical Sciences and Biotechnologies Sapienza University of Rome  Latina Italy"},{"name":"IRCCS Neuromed, Localit\u00e0 Camerelle  Pozzilli (IS) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Tavano","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Overi","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Ridola","sequence":"additional","affiliation":[{"name":"Department of Translational and 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