The thesis substantiates comprehensive diagnostics and treatment of hepatic encephalopathy (HE) in patients with chronic liver diseases (CLD) and concomitant pathologies by establishing regularities of clinical and laboratory and psychological disorders. New effective ways to improve the diagnostics and modeling of HE have been developed, and treatment has been optimized. The results show the importance of determining parameters of the serotonergic system for the comprehensive diagnostics of HE. This was confirmed by a rise in serotonin and tryptophan levels, and an increase in monoaminooxidase (MAO) activity in the brain, their decrease in the blood, and an increase in the activity of tryptophan hydroxylase (TPH) and in-doleamine 2,3-dioxygenase (IDO), which catalyse formation of this neurotransmitter. In the studied patients, we determined changes in the cytokine profile and the severity of anxiety and depressive disorders, and optimized diagnostic approaches to determine the criteria for the progression of hepatic encephalopathy in CLD of various etiologies. There was also a significant increase in the level of autoantibodies to neurospecific proteins, such as the basic cerebral antigen (BCA), S100 protein, neurospecific enolase (NSE), and myelin basic protein (MBP) in animals with HE. It was discovered for the first time that the modified regimen that envisages the introduction of choline alfoscerate (a highly effective drug for cognitive dysfunction in conditions of hepatic cirrhosis improved histological parameters, reduced the volume of damaged cells, decreased the severity of fibrosis and necroinflammatory activities in the tissue of this organ, and activated reparative regeneration. This indicates the relationship of the neuroprotector with the morphological state of liver tissue in conditions of experimental cirrhosis, and confirms the effectiveness of the new treatment regimen for hepatic cirrhosis. The hepatoprotective effect of choline alfoscerate was detected for the first time. We studied the effect of microbiotes on the pathogenesis of HE.
The proposed method of HE treatment, which solves the problem of improving the quality of treatment of hepatic encephalopathy in conditions of CLD, reduces the duration of treatment by influencing pathogenetic factors. The result is achieved by prescribing the neuroprotector choline alfoscerate, which restores brain dysfunction, penetrates the blood-brain barrier, stimulates the synthesis of neurotransmitters, helps to restore the cell membrane, and improves nerve impulse conduction.
