Tsyntar T. Clinical-pathogenic substantiation of nonalcoholic steatohepatitis differentiated treatment associated with chronic obstructive pulmonary disease.

The thesis presents a theoretical generalization and a new solution of a topical scientific task concerning increase of therapeutic treatment of patients with nonalcoholic steatohepatitis (NASH) with comorbid chronic obstructive pulmonary disease (COPD) on the basis of new scientific data on clinical-pathogenic peculiarities of the above comorbidity by means of differentiated administration of L-arginine considering G894T gene polymorphism of the endothelial NO-synthase. A сomorbid course of nonalcoholic steatohepatitis with chronic obstructive pulmonary disease is characterized by a higher occurrence of clinical-biochemical syndromes and more considerable changes of the blood lipid spectrum with less pronounced functional respiratory disorders, higher percentage of the adipose mass, greater level of the visceral fat and higher metabolic age index; changes in adipocytokine levels in the blood serum, manifested in increasing levels of leptin and resistin with decreased content of adiponectin. Іn case of comorbid course of nonalcoholic steatohepatitis and chronic obstructive pulmonary disease, the most pronounced systemic inflammation is found (іt is evidenced by a significant increase in the content of TNF?, TFG?1 and CRP in the blood serum and most significant oxidative stress and proteinase-inhibitory imbalance); endothelial dysfunction develops (іt characterized by increased levels of endothelin-1, sVCAM in the blood serum and a number of circulating desquamated endothelial cells with a maximum reduction of nitrites/nitrates in the blood, blood hypercoagulation and disorders of morphological and functional properties of erythrocytes). Іn case of comorbid course of nonalcoholic steatohepatitis and chronic obstructive pulmonary disease and allele T G894T available of endothelial NO-synthase polymorphism, more pronounced manifestations of endothelial dysfunction are found (higher levels of endothelin-1 and sVICAM and simultaneous low nitrate/nitrite levels in the blood) and more pronounced changes in the liver functional state (more manifested cytolysis, cholestatic syndromes and hepatic-cellular failure). The results of treatment are evaluated considering G894T polymorphism of endothelial NO-synthase in patients with nonalcoholic steatohepatitis associated with chronic obstructive pulmonary disease. Administration of L-arginine (increased dose and the term of treatment as much as twice with G894T and Т894Т genotypes available) in a comprehensive treatment is found to promote more pronounced improvement of the endothelial functional state, liver and endothelial function, and lipid spectrum of the blood.