THE EFFECT OF BICYCLOL ON THE STATE OF THE CONNECTIVE TISSUE COMPONENTS OF THE LIVER EXTRACELLULAR MATRIX IN THE COMPLEX THERAPY OF NON-ALCOHOLIC STEATOHEPATITIS WITH LIVER FIBROSIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Kotsіubiіchuk Zorіana Ya. , Khukhlina Oksana S. , Antonіv Aliona A. , Mandryk Olga Ye. , Garvasіuk Oleksandra V. , Roshchuk Oleksandra I. 
Published: February 2022

The aim of the research was to determine the probable effect of metformin, rosuvastatin and bicyclol on markers of hepatocyte cytolysis in patients with nonalcoholic steatohepatitis and diabetes mellitus type 2 with diabetic kidney disease, the degree of hepatocyte steatosis and stage of liver fibrosis, as well as the content of extracellular protein and carbohydrate components in the blood tissues that are markers of the intensity of liver fibrosis and the progression of non-alcoholic steatohepatitis.
Materials and methods. Studу of changes in the course of treatment of 60 patients with nonalcoholic steatohepatitis with type 2 diabetes mellitus and stage I–IV diabetic kidney disease was conducted, among whom 48 patients were diagnosed with mild non-alcoholic steatohepatitis and 12 – with moderate non-alcoholic steatohepatitis. A comorbid disease, i.e. type 2 diabetes mellitus of moderate severity, was registered in 100% of patients with nonalcoholic steatohepatitis: among them, 15 people had diabetes in the compensatory stage, 45 people – in the subcompensated stage. All patients with nonalcoholic steatohepatitis and type 2 diabetes had comorbid diabetic kidney disease, including 21 cases of stage I–II diabetic kidney disease, 20 cases of stage III diabetic kidney disease, and 19 patients with stage IV diabetic kidney disease.
Results. Analysis of the results of extracellular matrix connective tissue metabolism in the blood of patients with non-alcoholic steatohepatitis on the background of type 2 diabetes mellitus and diabetic kidney disease indicated that the inflammatory and dysmetabolic process contributed to a significant imbalance of connective tissue components. In particular, activation of anabolic collagen was shown on the basis of an increase in blood protein-bound oxyproline by 2 times (p < 0.05), as well as a decrease in the intensity of collagen catabolism – based on a decrease in blood free oxyproline by 1.4 times (p < 0.05), which probably occurred due to inhibition of collagenolytic activity of blood plasma (by 1.4 times, p < 0.05). That is, activated processes of collagen synthesis were accompanied by inhibition of its degradation and accumulation in the extracellular matrix. We also found a significant increase in the blood content of hexosamines by 1.5 times (p < 0.05) and accelerated degradation of carbohydrate-protein components of the matrix (with an increase in the content of unbound fucose by 2.6 times, (p < 0.05)).
Conclusions. The combination therapy with metformin, rosuvastatin in combination with Вicyclol in individuals with comorbid nonalcoholic steatohepatitis, type 2 diabetes mellitus and diabetic kidney disease for 3 months helped to eliminate the syndrome of cytolysis of hepatocytes, a significant reduction liver fibrosis intensity due to optimization of spectrum of connective tissue components of the extracellular matrix in the blood with a decrease in the content of markers of collagen anabolism, increase in the content of markers of collagen catabolism due to increased total collagenolytic activity of blood plasma, decrease in the content of hexosamines and carbohydrate protein markers.