The Role of Endothelial Dysfunction in the Progression Mechanisms of Non-Alcoholic Steatohepatitis in Patients With Obesity and Chronic Kidney Disease

Abstract

Introduction: The study increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine and in the world necessitates the research into mechanisms of mutual burden and the search for new factors in the pathogenesis of this comorbidity progression . The aim: To establish the role of endothelial dysfunction in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. Materials and methods: 135 patients were examined: of which 52 patients with non-alcoholic steatohepatitis with obesity I degree (1 group), 53 patients with nonalcoholic steatohepatitis with comorbid obesity of the I degree and chronic kidney disease of the І-ІІ stage (group 2). The control group consisted of 30 practically healthy persons of the corresponding age and sex. The average age of patients was (45.8 ± 3.81) years. Results: The results of the study showed that in patients with NASH, a significant increase in the content of NO in the blood was detected in comparison with the index in PHP (p <0,05) in group 1 - in 2,1 times, in the 2nd group - in 2,6 times (p <0,05). The role of nitrosative stress in the pathogenesis of NASH was proved, the confirmation of which is the increase in the concentration of nitrosothiols, peroxynitrite and other metabolites NO in the blood. Increased peroxynitrite formation due to the generation of NO by leukocytes is an important aspect of the damaging effect and inflammation process in NASH. Pathological hyperproduction of NO by endothelial cells and leukocytes from inflammatory infiltrates in the liver contributes to the development of nitrosative stress in NASH. The established hypernitrate in blood may also be considered compensatory in response to hyperproduction of ET-1 in all observational groups. Conclusions: Confirmation of the presence of endothelial dysfunction (ED) in patients with NASH with CKD resulted in a probable growth of the number of desquamated endothelial cells (DEC) in the 2nd group of patients in 1.9 times (p2 <0.05). Generation by neutrophils during the exacerbation of NASH of a significant number of active forms of oxygen and nitrogen and hyperproduction of endothelial cells and endometrial lymphocytes with progressive damage to the endothelium (growth of DEC) leads to significant ED, accompanied by mosaic angiospasm of the arteries due to hyperproduction of ET-1 and parectic vasodilatation of the veins of the portal vein system because of the hyperproduction of NO.

Endocan: A Biomarker for Hepatosteatosis in Patients with Metabolic Syndrome

“…Other than insulin resistance, one of the key mechanisms recently mentioned is the endothelial dysfunction in the progression of NAFLD. It would seem that progression of NAFLD related to increase of active forms of oxygen and nitrogen which leads to a significant arterial vasospasm and a progressive damage to the endothelium [21]. Therefore, the cardiovascular consequences and related metabolic disorders require a multidisciplinary approach to the management of NAFLD.…”

Non-alcoholic fatty liver and chronic kidney disease: Retrospect, introspect, and prospect

“…Proinflammation occurs through the NF-κB and Jun-N-terminal kinase (JNK) pathways; activation of adipose-specific JNK pathways has been shown to cause insulin resistance[ 48 , 49 ]. As NAFLD progresses to NASH, the inflammatory component is neutrophil-predominant and can cause systemic endothelial dysfunction (Figure 1 )[ 50 , 51 ]. Notably, IR leads to increased production of very-low-density lipoprotein and endoplasmic reticulum stress, both of which can cause podocyte damage in glomeruli[ 52 ].…”

Влияние Кверцетина На Клиническое Течение Неалкогольного Стеатогепатита И Диабетической Болезни Почек На Фоне Комплексного Лечения Больных Сахарным Диабетом Типа 2

“…Актуальність пошуку оптимальних способів лікування пацієнтів із коморбідним перебігом неалкогольного стеатогепатиту (НАСГ), що розвинувся на тлі цукрового діабету типу 2 (ЦД2), зумовлена тим, що зазначені захворювання мають низку спільних причинно-наслідкових механізмів, а за умов розвитку діабетичної хвороби нирок (ДХН) -ще і низку механізмів взаємообтяження [1][2][3][4]. Велика кількість досліджень, присвячених вивченню даної коморбідності, свідчить про значну актуальність цієї проблеми в Україні та у світі і низку не вирішених на сьогодні питань, які стосуються особливостей клінічного перебігу цих захворювань, не відомих досі механізмів їх прогресування і, найголовніше, нагальної потреби в розробці методів лікування шляхом усунення якомога більшої кількості ланок патогенезу їх взаємообтяження.…”