Researched object: steatosis of the liver and steatohepatitis of non-alcoholic and alcoholic genesis in combination with obesity (OB) and concomitant biliary tract (BT) pathology. Aim of the study: to improve the diagnosis, predict the course and increase the effectiveness of treatment patients with fatty liver disease in combination with obesity and biliary tract pathology based on comprehensive analysis of clinical and pathogenetic features and the development of flow forecasting algorithms based on indicators with the greatest predictive value. Methods of investigation: clinical and anamnestic; anthropometric (circumference of the waist (CT), circumference of the hips (CH), CT/CH ratio, height, weight, body mass index (BMI); biochemical: hepatic, protein, lipid complexes, intermediate and final parameters of lipid peroxidation (LPO) and antioxidant protection (AOP), lipid and phospholipid fractions: phospholipids (PL), phosphatidylcholine (PC), sphingomyelin (SM), free cholesterol (FC), cholesterol esters (CE), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE) connective tissue, markers of endogenous intoxication; immunoenzymometric: matrix metalloproteinase-1 (MMP-1), laminin (LN), hepatocyte growth factor (HGF); serological (indicators of cellular and humoral immunity, parameters of activated receptors on lymphocytes; instrumental: abdominal cavity ultrasound examination, puncture biopsy with histological examination of the liver structure, statistical methods. Scientific novelty: for the first time on a sufficient clinical material, the features of the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in combination with obesity and BT pathology have been established. It has been proved that during NAFLD under conditions of comorbidity, low rates of development and intensity of main clinical syndromes manifestations are observed in comparison with FLD of alcoholic etiology. It has been established that the main factors in the progression of NAFLD in the conditions of comorbidity are significant shifts in lipid and phospholipid fractions with a decrease in the levels of PL, PC, SM, and an increase in the FC, CE, toxic phospholipid degradation products - LPC, PE, which depend on body weight, the presence of various PT pathologies, the clinical form of NAFLD. For the first time it has been established that with the increase of BMI, depending on the BT pathology and the stage of NAFLD, the intensity of endogenous intoxication, oxidative stress increases, with the accumulation of intermediate and final products of LPO. For the first time, four types of AOP response were identified. Mathematical models for predicting the risk of transformation of non-alcoholic liver steatosis (NALS) into non-alcoholic steatohepatitis (NASH) under the conditions of comorbidity have been developed. An algorithm for the early diagnosis of NAFLD and forecasting the course of NASH have been developed. For the first time, an assessment of the immune status (IS) was made in each clinical case, taking into account the balance of the effector and regulatory links of immunity, and four variants of IS disorders were identified. It is proved that the increase in LN activity and the decrease in MMP-1 and HGF activity are more significant features of the progression of alcoholic steatohepatitis than the non-alcoholic. For the first time, it has been proved on histological material that with increasing body mass in patients with NAFLD, in conditions of comorbidity, fibrotic processes are intensified. The pathogenetic role of the use of ursodeoxycholic acid and glutamate arginine is substantiated against the background of standard treatment and lifestyle modification, which allowed to optimize the management of such category of patients.
