Mechanisms of hepatic sinusoidal endothelial cell dysfunction in cirrhosis

Abstract

One of the most persistent challenges in hepatology has been understanding why the hepatic sinusoidal vasculature, which in health provides an exceptionally permeable exchange surface between blood and hepatocytes, transforms into a rigid, poorly functioning barrier as cirrhosis develops. This research investigated the mechanisms and clinical correlates of hepatic sinusoidal endothelial cell (LSEC) dysfunction in 148 cirrhotic patients and 30 healthy liver donors at Cairo Institute of Technology between April 2015 and September 2019. Liver tissue was obtained during transjugular liver biopsy (cirrhotic patients) or from surgical liver resection margins (healthy controls), and assessed for LSEC phenotypic markers by immunohistochemistry (CD32b, stabilin-2, VEGFR2, von Willebrand factor [vWF], CD34, CD31), ultrastructural features by scanning electron microscopy (SEM), and sinusoidal nitric oxide availability by tissue nitrite/nitrate assay. Hepatic venous pressure gradient (HVPG) was measured simultaneously in all cirrhotic patients. Cirrhotic LSECs showed progressive loss of the differentiated phenotype: CD32b expression fell from 87.4±6.3% in healthy tissue to 24.8±14.6% in CTP-C cirrhosis (p