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Role of gut-derived endotoxins in porto-sinusoidal vascular disorder: comparison between patients with and without portal hypertension

Title: Role of gut-derived endotoxins in porto-sinusoidal vascular disorder: comparison between patients with and without portal hypertension
Authors: Overi D.; Pugliese N.; Carnevale R.; Nardelli S.; Tavano D.; Ridola L.; Mari A.; Merli M.; di Tommaso L.; Terracciano L.; d'Amati G.; Baiocchini A.; Forte M.; Frati G.; Carpino G.; Aghemo A.; Riggio O.; Gaudio E.; Gioia S.
Contributors: Overi, D.; Pugliese, N.; Carnevale, R.; Nardelli, S.; Tavano, D.; Ridola, L.; Mari, A.; Merli, M.; Di Tommaso, L.; Terracciano, L.; D'Amati, G.; Baiocchini, A.; Forte, M.; Frati, G.; Carpino, G.; Aghemo, A.; Riggio, O.; Gaudio, E.; Gioia, S.
Publisher Information: WILEY; 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Publication Year: 2025
Collection: Sapienza Università di Roma: CINECA IRIS
Subject Terms: endotoxemia; intestinal permeability; obliterative portal venopathy; porto‐sinusoidal vascular liver disorder
Description: BackgroundEtiopathogenesis of porto-sinusoidal vascular disorder (PSVD) is poorly known. The present study aimed to investigate alterations in gut barrier, bacterial translocation, and pro-aggregating/pro-coagulant state and their relationship with liver injury in patients with PSVD without portal hypertension (PH-) in comparison with PSVD with PH (PH+) and healthy controls.Methods34 patients with PSVD (17 PH+ and 17 PH-) and 17 healthy subjects were submitted to measurement of zonulin and lipopolysaccharides (LPS), markers of intestinal permeability, of s-Glycoprotein VI, sP-selectin, ADAMTS13 and von Willebrand factor (vWF), markers of platelet aggregation and vascular dysfunction, factor VIII and F1 + 2, markers of hypercoagulability. In 30 PSVD patients, a histomorphological/immunohistochemical study on liver biopsies was performed.ResultsPSVD PH- patients had higher serum levels of LPS, zonulin, vWF, factor VIII, sP-selectin, F1 + 2 and lower levels of ADAMTS13 compared to healthy controls. These alterations were even more pronounced in PSVD PH+. At histological analysis, compared to those of healthy subjects, livers of patients with PSVD PH- showed a higher number of TLR4+ macrophages and of platelets within sinusoids with signs of aggregation. Perivascular fibrosis and sinusoid capillarisation were higher too. PSVD PH- had a lower degree of obliterative portal venopathy and portal inflammation compared to patients PH+.ConclusionsEven before the development of PH, patients with PSVD exhibit increased intestinal permeability and bacterial translocation, related platelet aggregation, and hypercoagulability, suggesting that endotoxemia may play a pivotal role in the pathogenesis of vascular alterations underlying PSVD. Moreover, this study indicates that PSVD without and with PH represent different stages of the same disease.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40781803; info:eu-repo/semantics/altIdentifier/wos/WOS:001546228700001; volume:45; issue:9; firstpage:1; lastpage:13; numberofpages:13; journal:LIVER INTERNATIONAL; https://hdl.handle.net/11573/1745333
DOI: 10.1111/liv.70277
Availability: https://hdl.handle.net/11573/1745333; https://doi.org/10.1111/liv.70277
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.ADB5194A
Database: BASE