{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:39:09Z","timestamp":1792276749388,"version":"4.4.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T00:00:00Z","timestamp":1478304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T00:00:00Z","timestamp":1478304000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>Patients with cirrhosis may display impaired or enhanced platelet activation, but the reasons for these equivocal findings are unclear. We investigated if bacterial lipopolysaccharide (LPS) is implicated in platelet activation. In a cross\u2010sectional study, conducted in an ambulatory care clinic and hospital, comparing 69 cirrhosis patients and 30 controls matched for sex, age, and atherosclerotic risk factors, serum levels of LPS, soluble cluster of differentiation 40 ligand and p\u2010selectin (two markers of platelet activation), and zonulin (a marker of gut permeability) were investigated. <jats:italic toggle=\"yes\">Ex vivo<\/jats:italic> and <jats:italic toggle=\"yes\">in vitro<\/jats:italic> studies were also performed to explore the effect of LPS on platelet activation. Compared to controls, cirrhosis patients displayed higher serum levels of LPS (6.0 [4.0\u201017.5] versus 57.4 [43.4\u201087.2] pg\/mL, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0001), soluble cluster of differentiation 40 ligand (7.0 \u00b1 2.2 versus 24.4 \u00b1 13.3 ng\/mL, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0001), soluble p\u2010selectin (14.2 \u00b1 4.05 versus 33.2 \u00b1 15.2 ng\/mL, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0001), and zonulin (1.87 \u00b1 0.84 versus 2.54 \u00b1 0.94 ng\/mL, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.006). LPS significantly correlated with zonulin (<jats:italic toggle=\"yes\">r<\/jats:italic> = 0.45, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). <jats:italic toggle=\"yes\">Ex vivo<\/jats:italic> studies showed that platelets from cirrhosis patients were more responsive to the agonists independently from platelet count; this phenomenon was blunted by incubation with an inhibitor of Toll\u2010like receptor 4. <jats:italic toggle=\"yes\">In vitro<\/jats:italic> study by normal platelets showed that LPS alone (50\u2010150 pg\/mL) did not stimulate platelets but amplified platelet response to the agonists; Toll\u2010like receptor 4 inhibitor blunted this effect. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> LPS may be responsible for platelet activation and potentially contributes to thrombotic complications occurring in cirrhosis. (H<jats:sc>epatology<\/jats:sc> 2017;65:571\u2010581).<\/jats:p>","DOI":"10.1002\/hep.28853","type":"journal-article","created":{"date-parts":[[2016,9,19]],"date-time":"2016-09-19T09:00:32Z","timestamp":1474275632000},"page":"571-581","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":135,"title":["Low\u2010grade endotoxemia and platelet activation in cirrhosis"],"prefix":"10.1097","volume":"65","author":[{"given":"Valeria","family":"Raparelli","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Basili","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties,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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Napoleone","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Del Ben","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Nocella","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Bartimoccia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Lucidi","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Talerico","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliviero","family":"Riggio","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Violi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,11,5]]},"reference":[{"key":"hep28853-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jhep.2011.06.008","article-title":"Patients with liver cirrhosis suffer from primary haemostatic defects? 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