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MECHANISMS OF NONALCOHOLIC STEATOHEPATITIS PROGRESSION ON THE BACKGROUND OF OBESITY AND STAGE I-II CHRONIC KIDNEY DISEASE

Аuthors: A. A. Antoniv

Pages: 308–314

Abstract

         

The increase in the frequency of nonalcoholic steatohepatitis (NASH) comorbid course on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine and in the world necessitates conducting research on mechanisms of mutual burden and finding new factors for the progression pathogenesis of this comorbidity.

The purpose of the study was to establish the mutual burden and progression mechanisms of non-alcoholic steatohepatitis and chronic kidney disease in obese patients based on the study of protein and carbohydrate-protein components of the extracellular matrix, lipid profile of the blood, and functional state of the endothelium.

Material and methods. 114 patients with NASH were examined on the background of degree І-ІІ obesity, including: 52 patients with NASH (group 1) (without accompanying CKD), 62 patients with NASH with comorbid CKD, І-ІІ stage (group 2). The average age of patients was (45.8 ± 3.81) years. The control group consisted of 20 practically healthy persons (PHP) of the corresponding age and sex.

Results. We studied the dynamics of patients with non-alcoholic steatoatepatitus (NASH) with comorbid obesity and chronic kidney disease, І-ІІ stage (CKD), the role of hydrogen sulfide in the mechanisms of mutual burden and progression of comorbid diseases: hyperlipidemia, hyperproduction of extracellular matrix components (protein-bound and free hydroxyproline, glycosaminoglycans, fibronectin, hexosamines, sialic acids), osteoporotic proteins, proteinase-inhibitory imbalances (activation of proteolysis, collagenolysis), endothelial dysfunction (imbalance in generating nitrogen monoxide, endothelin-1, homocysteine).

Conclusions. In patients with NASH on the background of obesity, a significant increase in the synthesis of collagen and glycoproteins was observed, which was accompanied by an ineffective resorption of newly formed collagen due to inhibition of collagenolysis (CLA) on the background of proteinase inhibitors (α2-MG) activation, which was accompanied by hyperproduction of the growth factor fibroblasts, homocysteine, endothelin-1, deficiency in the liberation of hydrogen sulfide and nitrogen monoxide. Under the conditions of the comorbidity of NASH with the CKD of the 1st and 2nd stages, both collagen synthesis and resorption are activated, but the processes of anabolism prevail in spite of the compensatory activation of collagenolysis, with a significant hyperproduction of actinic-phase proteins, fibronectin, glycosaminoglycans, fibroblast growth factor and increased degradation of the extracellular matrix fucoglycoproteins and lead to progressive fibrosis of the liver and disturbance of its functions.

Keywords: nonalcoholic steatohepatitis, chronic kidney disease, obesity, hydrogen sulfide, endothelial dysfunction.

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