Value of Endothelial Dysfunction in the Pathogenesis of Portal Hypertension

Background: Until now it was thought that the main cause of portal hypertension is a mechanical obstruction of blood flow in the portal vein due to proliferation of connective tissue in the liver parenchyma (irreversible factor). The role of reversible factors remained underestimated. These include the following components: tone of the blood vessels, blood rheology, micro thrombosis, swelling of the liver parenchyma. The tone of hepatic blood vessels is provided by a number of factors, among which the most important is nitrogen monoxide (NO) – natural vasorelaxsing substance, produced by vascular endothelium. The role of endotheliumdependent factors in the pathogenesis of many chronic diseases is extensively studied for today, but the impact of endothelial dysfunction on liver hemodynamics and forming of portal hypertension is not clear yet. Aim & Objectives: The aim of our research was to examine the condition of hepatic blood flow in patients with portal hypertension, which developed on the background of chronic alcoholic steatohepatitis (ASH) and liver cirrhosis (LC), depending on the degree of endothelial dysfunction in these patients. Methods: Research was carried out at the Gastroenterological Department of Emergency Hospital in Chernivtsi. The study involved 63 patients with ASH, having signs of initial stage of portal hypertension (study group 1). Also 31 patients with LC with expressed portal hypertension were examined (study group 2). As controls 62 ASH patients without any signs of portal hypertension were examined (control group). Exclusion criteria in both groups were: old age, the presence of cardiac failure, kidney failure and other diseases in decompensate stage. Results: Summarizing the results obtained in the research process, it should be noted that in all examined patients with chronic alcoholic hepatitis EGD and Doppler signs of preclinical stages of hyperkinetic type of portal hypertension were observed. Absence of cirrhotic changes of liver tissue in these patients is confirmed by histopathological study of liver biopsies. Blood tests have revealed the decreasing of NO level (endothelial vasorelaxsing factor) and depression of endothelium-dependent fibrinolytic activity of plasma. Doppler examination of the brachial artery patients of the 1-st group have revealed decreased endothelium-dependent vasodilation (ЕDVD) 7,3±0,18% (against 12,9±0,22% in controls (р<0,05)). Amongst 82 % patients of the 2nd group ЕDVD was only 5,4±0,15%, what is significantly less, than in 1-st and control groups (р<0,05). Amongst 18 % patients of 2nd group during conducting of test for reactive hyperemia it was registered the paradoxical vasoconstrictive reaction, indicating a more expressed endothelial dysfunction. The analysis of the data determined the availability of reverse International Journal of Collaborative Research on Internal Medicine & Public Health Vol. 4 No. 6 (2012) 1041 correlation between the degree of portal hypertension and the level of NO in blood (r=0.87) and between the degree of portal hypertension. and EDVD index (r=0,54) with a high degree of probability, indicating the important pathogenetic role of endothelial dysfunction in the development and progression of portal hypertension. Conclusion: There are manifestations of endothelial dysfunction in patients with portal hypertension, which have been developed on the ASH background. The gradual increasing severity of portal hypertension is observed in the same moment with the deterioration of the endothelium functional condition. The imbalance of endothelium-dependent vasoactive substances is an important part of potentiating of hepatic hemodynamic failure and formation of high pressure in the portal vein system in such patients.. Prospects for further investigations is the search for medications to correct endothelial dysfunction in order to improve results of treatment of patients with portal hypertension on the chronic alcoholic steatohepatitis background.