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.