The role of endothelial dysfunction in the progression mechanisms of non-alcoholic steatohepatitis in patients with obesity and chronic kidney disease.

OBJECTIVE: 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. PATIENTS AND METHODS: 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: 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. CONCLUSION: 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.

The role of hydrogen sulfide in the progression mechanisms of non-alcoholic steatohepatitis and chronic kidney disease.

OBJECTIVE: Introduction: The steady 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. The aim: To establish the role of hydrogen sulfide in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 114 patients with NASH were examined on the background of obesity of І-ІІ degree, including: 52 patients with NASH (group 1) (without accompanying CKD), 62 patients with NASH with a comorbid CKD І-ІІ degree (group 2). The control group consisted of 20 practically healthy persons (PHPs) of the corresponding age and sex. RESULTS: Results: The obtained data testify that a significant increase in the synthesis of collagen and glycoproteins in patients with NASH, which arose on the background of obesity, that comorbid with CKD, which was accompanied by an ineffective resorption of newly formed collagen due to insufficient activation of collagenolysis and proteolysis, a significant imbalance in the system of connective tissue metabolism. CONCLUSION: Conclusions: A significant increase in the synthesis of collagen and glycoproteins (fibronectin) in patients with NASH, which was observed on the background of obesity, was established, which is accompanied by an ineffective resorption of newly formed collagen due to inhibition of collagenolysis against activation of proteinase inhibitors (α2-MG).

Clinical and pathogenetic features of nonalcoholic steatohepatitis for comorbidity with bronchial asthma on the background of obesity.

OBJECTIVE: Introduction: The comorbid flow of non-alcoholic steatohepatitis (NASH) and bronchial asthma (BA) on the background of obesity is often recently drawn to the attention of both practitioners and researchers . The aim of our study was to study the changes in the functional state of the liver and the dependence of the external respiration function in patients with non-alcoholic steatohepatitis in combination with bronchial asthma and obesity. PATIENTS AND METHODS: Materials and methods: The study was attended by 50 people aged from 30 to 50 years (average age 42 years), of which 40% were men and 60% women. Of these, 30 patients with obesity I degree (BMI greater than 30 kg / m2) non-alcoholic steatohepatitis was detected, and in 20 of patients, non-alcoholic steatohepatitis was combined with obesity of the I degree and persistent bronchial asthma of moderate severity. Duration of the disease was from 2 to 6 years. The control group consisted of 20 practically healthy persons (PHPs) of the corresponding age and sex. RESULTS: Results: In patients with NASH with comorbid BA and obesity I degree there are more noticed syndromes of cytolysis and cholestasis, mesenchymal inflammation, more significant changes in the liver, as evidenced by the low AST/ALT ratio in this group. Patients with non-alcoholic steatohepatitis on the background of obesity of the I degree with the addition of bronchial asthma of moderate severity and the persistent flow at the exacerbation phase, the content in the blood of markers of the activity of cytolysis of hepatocytes increases (increased activity of aminotransferases serum, p <0,05), cholestasis (increased contentof direct bilirubin in the blood, p <0,05, cholesterol activity, p<0,05, gamma-glutamyltransferase activity, p <0,05 and alkaline phosphatase, p <0,05) and mesenchymal inflammation (increase in the thyme test, p <0,05), which testifies to the aggravating factor and the impact of BA on the course of NASH. CONCLUSION: Conclusion: The presence of visceral obesity and nonalcoholic steatohepatitis in patients with bronchial asthma leads to the accumulation of its clinical course, the deepening of changes in the function of external respiration by obstructive type (a possible decrease in FEV1 and PEF, p<0.05). The presence of obesity and NASH contributed to the development of restrictive type of respiratory insufficiency in the form of a possible decrease in Vital capacity (VC, p<0,05) in patients without BA, and in patients with NASH and obesity with BA, which significantly aggravated its course.