Chereliuk N. Optimization of early diagnosis of non-alcoholic fatty liver disease on the background of obesity and overweight, taking into account the main phylotypes of gut microbiota and markers of inflammation

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0822U100976

Applicant for

Specialization

  • 222 - Медицина

03-11-2022

Specialized Academic Board

ДФ 64.568.003

Government Institution "L.T.Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine"

Essay

Against the background of the steady trend of increasing prevalence of overweight and visceral obesity, there is the increase in the incidence of non-alcoholic fatty liver disease, which is becoming one of the most common causes of liver disease worldwide and in Ukraine in particular. The key issue in the management of patients with non-alcoholic fatty liver disease is the timely diagnosis of fibrosis at the early stage, because the stage of fibrosis is the most important factor that correlates with the course of the disease both in the reverse direction and in the direction of progression with an increase in mortality in this group of patients. Therefore, the aim of the work was to optimize the early diagnosis of fibrosis in non-alcoholic fatty liver disease patients with obesity and overweight by studying the ratio of Firmicutes/Bacteroidetes phylotypes of gut microbiota, molecular genetic factors: microRNA-122, microRNA-34a, as well as pro-inflammatory markers: C-reactive protein and tumor necrosis factor-alpha. The dissertation research is based on a comprehensive examination of 140 patients, among which the main group consisted of 120 patients with non-alcoholic fatty liver disease and 20 healthy age- and sex-matched volunteers. 120 patients of the main group were divided into two subgroups depending on body mass index. The first subgroup included 85 patients with concomitant obesity. The second subgroup included 35 patients and overweight For the first time in the Ukrainian population, a comprehensive assessment of the qualitative composition of the gut microbiota by main phylotypes (Firmicutes, Bacteroidetes, Actinobacteria, and other phylotypes with the calculation of the Firmicutes/Bacteroidetes ratio) was carried out in patients with non-alcoholic fatty liver disease against the background of obesity and overweight; analyzed their correlations with the levels of microRNA-122, microRNA-34a, high-sensitivity C-reactive protein and factor tumors-alpha. The relationship between the composition of the gut microbiota and the degrees of steatosis and fibrosis was analyzed for the first time; determined the relationship of the main phylotypes of the gut microbiota with the pathogenetic links of the development of non-alcoholic fatty liver disease, in particular microRNA-122, microRNA-34a, high-sensitivity C-reactive protein and factor-alpha tumors, as well as lipid and carbohydrate disorders. For the first time, the expediency of using certain parameters as diagnostic markers of fibrosis was investigated. An algorithm for identifying groups of patients with non-alcoholic fatty liver disease with fibrosis has been developed, which includes a step-by-step examination with the determination of anthropometric indicators, cytolytic, metabolic parameters, molecular genetic and biological factors, which allows stratifying patients into a group that requires in-depth examination and intensive treatment.

Files

Similar theses