The dissertation presents a theoretical generalization and a new solution to the current scientific and practical problem of internal diseases, which is to improve the diagnosis and increase the effectiveness of treatment of patients with alcoholic liver disease combined with hypertension, based on new scientific data on clinicalpathogenetic features of this comorbidity by the use of atorvastatin.
It was found that the course of alcoholic liver disease (chronic alcoholic hepatitis and alcoholic liver cirrhosis), combined with hypertension, is characterized by greater severity of major clinical and laboratory syndromes and morphological changes of the liver (increased specific hemorrhage, optical density of collagen fibers with increasing processes in them oxidative modification of proteins and limited proteolysis, intensification of limited proteolysis processes in hepatocytes) compared with patients without concomitant hypertension.
In the presence of concomitant hypertension in patients with alcoholic liver disease, changes in the functional state of the endothelium are characterized by higher than in patients without hypertension, the content of sICAM-1 (by 6.2 % – in patients with chronic alcoholic hepatitis and by 8.1 % – in patients with alcoholic liver cirrhosis) and total nitrogen monoxide (by 29.6 % – in patients with chronic alcoholic hepatitis) with a lower (by 19.7 %) level of nitrogen monoxide in patients with alcoholic liver cirrhosis. Dysfunction of the endothelium is accompanied by changes in the hemocoagulation of homeostasis with less (compared with patients without hypertension) antithrombin III activity (by 11.9 % – in the combination of chronic alcoholic hepatitis and hypertension) and XIII factor of blood clotting (by 8 % – in the combination of chronic alcoholic hepatitis and arterial hypertension, by 10.2 % – in the combination of alcoholic cirrhosis of the liver and arterial hypertension) with a significantly higher concentration of D-dimer (by 11.8 % – in the combination of alcoholic cirrhosis of the liver and arterial hypertension).
A decrease in the prevalence of genotypes was found -786 TC and -786 CC in the e-NOS gene (T-786C) with increasing frequency of -786 TT genotype in alcoholic liver cirrhosis (χ2 = 7.02; p <0.01). At the same time, long-term alcohol abuse revealed an association between the -786 TC genotype for the e-NOS gene and the development of alcoholic hepatitis. Polymorphic variants of the PNPLA3 (C10109G), CD 14 (C-159T) genes are not additional risk factors for alcoholic liver disease. Combinations of the TC / CT genotypes for the eNOS / CD14 and TC / CT / GG genes for the eNOS / CD14 / PNPLA3 genes significantly reduce the risk of cirrhotic liver disease, including in the case of prolonged alcohol abuse.
The development of arterial hypertension in patients with alcoholic liver disease is associated with the presence of a homozygous TT genotype for a polymorphic variant of the eNOS gene (T-786C). In this group of patients, the frequency of TT genotype was 46.8 %, ST – 41.9 % and SS – 11.3 %. For patients with alcoholic liver disease without concomitant hypertension, the corresponding frequencies were: TT – 25.7 %, CT – 57.1 % and SS – 17.2 %. It was found that in patients with alcoholic liver disease combined with hypertension by TT genotype of the polymorphic variant of the e-NOS gene (T-786C) higher levels of ET-1 and sICAM-1 at lower levels of total nitric oxide compared to patients without arterial hypertension. The most probable differences in the indicators of systemic inflammation (IL-10, CRP, TGFβ1) and the marker of oxidative stress (8-isoprostane) are characteristic of the TT genotype for the polymorphic variant of the eNOS gene (T-786C) in patients with alcoholic liver disease with hypertension compared with the course of alcoholic liver disease. Hemostasis parameters such as APTT, antithrombin III, D-dimer, spontaneous platelet aggregation and factor XIII were associated with the TT genotype in patients with ACP with hypertension by the polymorphic variant of the eNOS gene (T-786C).
The use of atorvastatin in the complex treatment of patients with alcoholic liver disease (chronic alcoholic hepatitis and alcoholic liver cirrhosis), combined with hypertension, leads to improved endothelial function (decreased levels of endothelin-1, total nitric oxide and sICAM-1); decrease in the intensity of systemic inflammation (confirmed by a decrease in C-reactive protein, tumor necrosis factor-α, interleukin-10, transforming growth factor β1) and oxidative stress (accompanied by a decrease in serum 8-isoprostane and ceruloplasmin) on the background of reduction of dyslipoproteinemia (reducing the level of total cholesterol, low-density lipoprotein cholesterol, triglycerols while increasing the content of high-density lipoprotein cholesterol).
