Наукові праці. Кафедра внутрішньої медицини № 1

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    Modern methods of diagnosis and screening of non-alcoholic fatty liver disease and its stages (review)
    (2022) Zhelezniakova, Natalia; Babak, Oleg; Aleksandrova, Tetiana
    The review features the problem of diagnosing one of the most common pathologies of the contemporary world –non-alcoholic fatty liver disease (NAFLD). Data from experimental and clinical studies on the importance of various instrumental and biochemical methods of non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) and liver fibrosis (LF) are pre-sented. New non-invasive diagnostic methods of NASH and LF are discussed.
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    Markers of liver damage in comorbidity of nonalcoholic liver disease and hypertension
    (2020) Babak, Oleg; Prosolenko, Kostyantyn
    Objective: to study the features of liver damage and to study the main factors of influence on this process with comorbidity between non-alcoholic fatty liver disease and essential hypertension or renoparenchymal arterial hypertension. Materials and methods. The object of the study was 269 patients, included in three groups: group 1 - patients with non-alcoholic fatty liver disease (60 patients), group 2 - patients with comorbidity of non-alcoholic fatty liver disease and essential hypertension (121 patients), group 3 - patients with comorbidity of non-alcoholic fatty liver disease and renoparenchymal arterial hypertension (88 patients). The control group consisted of 20 healthy individuals of the same age and gender categories. Clinical examination of patients included an assessment of the parameters of an objective examination: in particular, anthropometric data and blood pressure according to standard methods. We studied both laboratory and instrumental markers of liver damage. To diagnose the condition of the liver and blood vessels in all patients, an ultrasound method was used. Some patients (212 people) underwent the Fibromax test. To assess the severity of insulin resistance, the HOMA index was calculated. Glomerular filtration rate was determined by the formula CKD-EPI. The level of cytokeratin-18 in blood plasma was determined by ELISA. Results and its discussion. A highly significant difference was found for most indicators between the groups of patients and the control group. The greatest difference was found in levels of transaminases (ALT and AST), gamma-glutamyl transpeptidase, as well as cytokeratin-18 (p <0.001). The most pronounced increase in transaminases was observed in patients of group 3. The levels of gammaglutamyltranspeptidase in patients of all three groups significantly exceeded the corresponding parameters of the control group, were the highest in group 3 - 68.10 ± 33.31 U/l. Moreover, this the indicator did not significantly differ between groups 2 and 3 (p> 0.05). Cytokeratin-18 was significantly increased in patients with nonalcoholic fatty liver disease, and was significantly different between all groups. Fewer patients with no hepatic fibrosis were recorded in group 1. We found significant correlation between the duration of non-alcoholic fatty liver disease and all markers of liver damage in group 1. Also, markers of liver damage positively correlated with body mass index, which indicates an important role obesity in the pathogenesis of non-alcoholic fatty liver disease. Given the correlations with the indicators of adiponectin, malondialdehyde, tumor necrosis factor-alpha, HOMA, we can state the important role of inflammation, oxidative stress, insulin resistance in the pathogenesis and development of non-alcoholic fatty liver disease. A strong negative correlation between cytokeratin-18 and glomerular filtration rate of - 0.402 (p <0.001) was also found. Important in our opinion were the positive relationships between indicators of hepatic damage and blood pressure in groups 2 and 3, which may indicate a relationship within comorbidity. In general, the largest number of strong correlation bonds were found for cytokeratin-18, and the smallest for gammaglutamyltranspeptidase. The profile of the correlation between the main indicators did not differ much from group 2. Using ANOVA dispersion analysis, we found a close relationship between the degree of liver steatosis and the main markers of liver damage ALT, AST, GGT, cytokeratin-18, fibrotest, and actitest. The highest Fisher coefficient was recorded for cytokeratin-18 - F = 118.58 (p <0.001), actitest - F = 102.18 (p <0.001), fibrotest - F = 95.03 (p <0.001), gamma-glutamyltranspeptidase - F = 26.6 (p <0.001). Such data indicate a close relationship between the processes of fat accumulation, inflammation, and apoptosis in the liver with non-alcoholic fatty liver disease in the presence or absence of comorbidity with essential hypertension or renoparenchymal arterial hypertension. Conclusions. For patients with non-alcoholic fatty liver disease, in the presence of its comorbidity with essential hypertension or renoparenchymal arterial hypertension, a more pronounced increase in gamma-glutamyl transpeptidase, cytokeratin-18 and actitest was characteristic, which may indicate the presence of more active processes of inflammation and hepatic apoptosis. A negative effect of comorbidity with essential hypertension or renoparenchymal arterial hypertension on liver fibrosis was also found. Markers of liver damage are associated with the duration of non-alcoholic fatty liver disease activity, body mass index, adiponectin, markers of inflammation and oxidative stress, kidney function. The degree and list of correlation relationships differ with non-alcoholic fatty liver disease depending on the presence or absence of comorbidity with essential hypertension or renoparenchymal arterial hypertension. Severe liver steatosis strongly affects the processes of hepatic inflammation, fibrosis and apoptosis with the comorbidity of non-alcoholic fatty liver disease with essential hypertension or renoparenchymal arterial hypertension.
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    Тhe role of pentraxin-3 in non-invasive diagnosis of liver fibrosis in patients with non-alcoholic fatty liver disease
    (2020) Бабак, Олег Якович; Александрова, Тетяна Миколаївна; Aleksandrova, Tetiana; Babak, Oleg
    The aim of the study: to determine the diagnostic value of Pentraxin-3 for the stages of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: 40 patients with NAFLD were examined, the mean age was (38.0 ± 4.1) years. The control group was created by 20 healthy individuals. There were no statistically significant differences in gender and age distribution of groups. Transient electrography of the liver was performed using an ultrasound scanner - SIEMENS - ACUSON S 3000. Determination of the level of pentraxin-3 in blood plasma was performed using the enzyme-linked immunosorbent assay using the ELISA kit. Results and Discussion: It was found that the level of Pentraxin-3 depend on the degree of liver fibrosis stage in patients with NAFLD. There was a significant increase of studied biomarker in the case of progression of liver fibrosis stage. Thus, in patients with liver fibrosis stage F0 the level of pentraxin-3 was (254, 35±44, 4) pg/ml, stage F1 – (421, 9±31, 46) pg/ml, and in stage F2 - respectively (430,9±35,86) pg/ml (p<0.05). Conclusion: In patients with NAFLD, the blood plasma’s level of Pentraxin-3 had a significant tendency to increase with the progression of the liver fibrosis stage (p<0.05), which confirms the possibility of using this biomarker in the diagnosis of liver fibrosis stages
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    Non-alcoholic fatty liver disease and hypertension: clinical variability of comorbidity
    (2020-11) Рождественська, Анастасія Олександрівна; Железнякова, Наталя Мерабівна; Rozhdestvenska, Anastasiia; Babak, Oleg; Zhelezniakova, Natalia
    Introduction. Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and considerable attention is paid to the comorbidity of NAFLD with hypertension (HT), which affects around one-third of the world's population. The combination of NAFLD with hypertension has been suggested to have a mutual potentiating effect, and hypertension affects the severity of NAFLD. The purpose: to study the features of the clinical manifestation of NAFLD in patients with hypertension. Materials and methods. The study included 115 patients with NAFLD at the stage of nonalcoholic steatohepatitis. The main group consisted of 63 patients with NAFLD and HT, the comparison group included 52 patients with isolated NAFLD, and the control group was composed of 20 healthy volunteers. Patients underwent anthropometric measurements, evaluation of biochemical markers of liver functional activity, lipid profile and carbohydrate metabolism changes, C-reactive protein (CRP) levels. Results. A significant increase in the proportion of patients with active complaints in the group of patients with NAFLD with HT (subjective signs of liver damage, manifestations of dyspeptic and asthenic syndrome) was detected. Significant differences were found in almost all anthropometric indicators in both groups of patients with NAFLD in comparison with the control group. The level of CRP had significant differences and was 7.90 mg/l (95% CI = 7.96-8.75 mg/l), 6.55 mg/l (95% CI = 6.47-7.57 mg/l) and 2.07 (95% CI = 1.83-2.85 mg/l) in patients with NAFLD and HT, isolated NAFLD and the control group, respectively (p <0.001). Fasting glucose levels were significantly higher in both groups of examined patients with NAFLD compared with controls. Significant differences were found in the levels of total cholesterol, VLDL cholesterol, HDL cholesterol and atherogenic factor in patients with NAFLD depending on concomitant HT. There was no significant difference between LDL cholesterol and triglycerides in the two groups of patients with NAFLD. Conclusions. Based on the obtained data, it can be stated that GC in patients with NAFLD determines important deviations in the clinical manifestation of the disease and can be considered as a trigger factor for the progression of NAFLD.
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    Cluster analysis of the pathogenetic relationships of metabolic parameters in patients with non-alcoholic fatty liver disease on the background of hypertension
    (2019) Babak, Oleg; Bashkirova, Anna
    The aim of the study was to conduct a cluster analysis of pathogenetic relationships between metabolic parameters, endothelial lipase levels, the severity of steatosis, and clinical parameters in patients with non-alcoholic fatty liver disease with hypertension. To analyze pathogenetic relationships, a cluster analysis was performed with the distribution of parameters into 4 clusters using the Ward's method. The most dense metabolic link by cluster analysis endothelial lipase forms with NAFLD liver fat score (2.639 cu), HbA1C (2.084 cu), total cholesterol (2.272 cu), and alcohol units (2.797 cu).
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    Results of correction of the hepatic steatosis on the background of hypertension and overweight with help of essential phospholipid complex
    (2019-03) Babak, Oleg; Bashkirova, Anna
    One of the unfavorable factors contributing to the forma- tion of cardiovascular risk in non-alcoholic fatty liver disease (NAFLD) on the background of hypertension is the low level of HDL cholesterol, in the metabolism of which the activity of endothelial lipase (EL) plays a leading role. The liver plays an important role in the formation of dyslipidemia and is a target for lipid metabolism disorders, representing one of the pathoge- netic stages of NAFLD formation, which dictates the search for ways of drug “support” of hepatocytes. The aim of the research was to study the effectiveness of es- sential phospholipids in the complex therapy of patients with NAFLD, hypertension and overweight, taking into account the ynamics of laboratory and instrumental examinations and EL blood level. 52 patients with NAFLD on the background of hypertension and overweight have been examined. The control group con- sisted of 20 practically healthy people. All patients were divided with accordance of age and sex. Dietary nutrition with reduction of simple carbohydrates and fats was recommended for patients and treatment with essential phospholipids for 6 months at a dose of 2 capsules 3 times a day was prescribed. 16 patients of the main group showed complete compliance till the end of the course of treatment. The concen- tration of EL was determined by the ELISA using the Aviscera Bioscience INC reagents kit (USA). The complex of essential phospholipids as additional com- ponent for diet showed an effective decrease in the severity of hepatic steatosis in combination with the reduction of insulin re- sistance, as well as the restoration of normal pathogenetic func- tional links between HDL and endothelial lipase in patients with NAFLD on background of hypertension. Thus essential phospholipids can be recommended to reduce CVD and comorbidity for all patient`s with these diseases, which was mentioned above, despite the range of steatosis.
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    The role of endothelial lipase in the diagnosis of cardiovascular risk in patients with non-alcoholic fatty liver disease in hypertension and insulin resistance subjects
    (2018-09) Bashkirova, Anna; Babak, Oleg
    Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common disease in hepatology, and is also often accompanied by hypertension. Insulin resistance(IR) and endothelial dysfunction, in which metabolism endothelial lipase (EL) plays a leading role, are links in a chain and play an important role in the development of cardiovascular risk (CVR). Therefore, our aim was to determine the blood levels of EL for the early detection of CVR in patients with NAFLD in hypertension and IR subjects. Increased levels of EL is inherent in all patients with NAFLD and hypertension. However, in patients with NASH and hypertension formed an additional association between the level of EL and HbA1С, which allows to consider EL as an additional predictor of CVR.
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    Parameters of lipid metabolism and severity of liver steatosis in patients with non-alcoholic fatty liver disease on the background of hypertension depending on the status of carbohydrate metabolism
    (2018-12) Babak, Oleg; Bashkirova, Anna
    The aim of the study was to establish relationships between the parameters of lipid metabolism, the severity of liver steatosis and the concentration of endothelial lipase (EL) serum levels depending on the state of carbohydrate metabolism and the presence of type 2 diabetes . 60 patients with non-alcoholic fatty liver disease (NAFLD) on the background of hypertension and overweight have been examined. The distribution of the examined patients was carried out in the following groups: group 1 - patients with hypertension without an increase in NAFLD liver fat score normal weight (n = 8); Group 2 - with hypertension without increse in NAFLD liver fat score with overweight (n = 8); group 3 - with liver steatosis without type 2 diabetes (n = 10); group 4 - with liver steatosis and type 2 diabetes (n = 10); group 5 - with laboratory signs of steatohepatitis without type 2 diabetes (n = 16); group 6 - with laboratory signs of steatohepatitis and type 2 diabetes (n = 8). All patients were divided with accordance of age and sex. The control group consisted of 20 healthy individuals. All patients with NAFLD on the background of hypertension and the presence of type 2 diabetes had significantly (p <0.001) higher hyperinsulinism (32.27 + 4.71 vs. 20.75 + 9.5 mkU/ml) and significantly (p <0.001) increased values of insulin resistance index HOMA-IR (9.52 + 4.21 against 4.76 + 2.23 U), which testifies in favour of type 2 diabetes. In all patients with NAFLD on the background of hypertension, there are proatherogenic changes in lipid status, the presence of which is exacerbated with obesity and the severity of steatosis. It is most evident in patients with steatohepatitis in combination with type 2 diabetes. The level of EL is significantly higher in patients with steatosis, regardless of the presence of diabetes and with steatohepatitis without diabetes compared with controls and patients with hypertension and normal weight. Significantly high levels of endothelial lipase were found in patients with steatohepatitis and diabetes. Correlation analysis between the HbA1c and EL levels showed a reliable direct relationship between the parameters. So the level of EL in patients with hypertension in combination with the severity of liver steatosis is significant relative to atherosclerotic vascular lesions and prognostic as the occurrence of cardiovascular complications.
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    Biomarkers usage in minimally invasive diagnosis of nonalcoholic steatohepatitis in nonalcoholic fatty liver disease patients
    (2017) Babak, Oleg; Molodan, Volodymyr; Lapshyna, Kateryna; Prosolenko, Kostyantyn
    Plasma CK-18 and FGF-21 levels are increased in patients with NASH and also associate with atherogenic dyslipidemia and impaired liver enzyme activity. Study plasma levels of CK-18 and FGF21 allows to establish the presence of NASH in patients with NAFLD. The findings suggest the possibility of using these biomarkers for minimally invasive screening diagnosis of NASH and represent the perspective of further research.
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    Routes of implementation and factors of escalation of systemic inflammatory response in comorbidity of chronic obstructive pulmonary disease and chronic pancreatitis
    (2017) Zhelezniakova, Natalia; Babak, Oleg
    The study aimed to determine mechanisms of implementation of systemic inflammatory syndrome in patients with comorbidity of chronic obstructive pulmonary disease and chronic pancreatitis. A total of 238 patients have been examined: 131 patients with chronic obstructive pulmonary disease in combination with chronic pancreatitis (main group) and 107 patients with an isolated chronic obstructive pulmonary disease (comparison group). Standard values were obtained while examining 20 almost healthy patients of the same age and gender, who made up the control group. Concentrations of cytokines: interleukin-1β, -2, -4, -6, -8 and tumor necrosis factor-α, quantification of C-reactive protein and ceruloplasmin activity in the blood serum has been de- termined. Statistical analysis has been performed on workstation by means of “Microsoft Excel” and “STATISTICA 6.0” software. The study showed that chronic obstructive pulmonary disease exacerbation was accompanied with a significant increase in the activity of systemic inflammation mediators – the cytokine cas- cade and acute phase reactants, in both groups of patients with chronic obstructive pulmonary disease. However, the comparative analysis of the examined groups has proved the significant dif- ference in cytokine status of patients with comorbidity of chronic obstructive pulmonary disease and chronic pancreatitis and in patients with isolated chronic obstructive pulmonary disease. Sig- nificant differences were found out in all investigated indices – IL-1β, IL-2, IL-4, IL-6 and TNF-α, except IL-8. Similar trends were observed in the concentrations of acute phase proteins – C-reac- tive protein and ceruloplasmin, whose levels in patients with comorbid disorders were significantly higher than those figures of persons with isolated chronic obstructive pulmonary disease. Thus, it can be concluded that the presence of concomitant chronic pancreatitis in patients with chronic obstructive pulmonary disease potentiates activation of systemic inflammatory re- sponse that can be caused by formation of autoimmune reactions in an organism thereby contrib- uting to a rapid progression of the pathological process and earlier formation of complications.