Role of Gut-Derived Endotoxins in Porto-Sinusoidal Vascular Disorder: Comparison Between patients with and without portal hypertension.

BACKGROUND: Etiopathogenesis 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. METHODS: 34 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. RESULTS: PSVD 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+. CONCLUSIONS: Even 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.