Наукові праці. Кафедра внутрішньої медицини № 1

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    Comparison of structural and functional vascular disorders in patiets with comorbidity of non-alcoholic fatty liver disease and two types of arterial hypertension
    (2023) Molodan, Volodymyr; Panchenko, Galyna; Prosolenko, Kostyantyn; Lapshyna, Kateryna; Shalimova, Anna
    Background: The aim was to conduct a comparative assessment of structural and functional vascular disorders in patiets with comorbidity of non-alcoholic fatty liver disease (NAFLD) and two types of arterial hypertension (HTN). Material and methods: The study included 329 patients 18–66 years old. All patients were divided into five groups: patients with comorbidity of NAFLD and primary HTN (121 subjects), patients with comorbidity of NAFLD and renal parenchymal HTN (88 subjects), patients with NAFLD (60 subjects), patients with primary HTN (30 subjects), patients with renal parenchymal HTN (30 people). The control group consisted of 20 healthy individuals of similar age and gender categories. Results: In the comparative analysis of the structural and functional ultrasonographic parameters of vessels, no significant differences between two comorbidity groups NAFLD + primary HTN and NAFLD + renal parenchymal HTN were found. The influence of AH and degree of liver steatosis on ultrasound indicators of arteries in examined patients with comorbidity was evaluated by MANOVA analysis. The influence of the HTN factor and the influence of the liver steatosis factor were evaluated separately, after which the influence of the comorbidity factor, i.e., the combined influence of these factors and one or another indicator, was evaluated. The additive effect of the factors of AH and liver steatosis was identified according to the parameters: intima media thickness, pulse wave velocity in the carotid artery, pulse wave velocity in the abdominal aorta and endothelial-related vasodilation, which indicates an important comorbid effect of NAFLD and primary/renal parenchymal HTN on the structural and functional state of arteries. Conclusions: There are no differences between the structural and functional indicators of arteries in patients with comorbidity of NAFLD + primary HTN and NAFLD + renal parenchymal HTN. The factor of the presence of HTN and the degree of liver steatosis significantly affect structural and functional indicators of the studied arteries.
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    Kallistatin, IL-10, IL-1β and hsCRP in the diagnosis of non-alcoholic fatty disease on the background of hypertension
    (2022) Rozhdestvenska, Anastasiia; Zhelezniakova, Natalia
    Background: Non-alcoholic fatty liver disease (NAFLD) affects 25% of the adult population and often develops in comorbidity with hypertension (HT). ROC-analysis allow to assess the diagnostic potential of biomarkers for liver fibrosis detection in NAFLD patients. Objective: To evaluate the kallistatin, IL-10, IL-1β and hsCRP role in determining of development and progression of liver fibrosis in NAFLD and HT patients. Methods: 63 patients with NAFLD on steatohepatitis stage and HT and 52 patients with isolated NAFLD were observed. Kallistatin, IL-10, IL-1β and hsCRP levels were determined by enzyme-linked immunosorbent assay. Results: The kallistatin showed significant potential in diagnosing the occurrence and progression of liver fibrosis in patients with NAFLD and HT (AUC=0.975, p=0.003, Sensitivity (Se)=95%, Specificity (Sp)=100%; AUC=0.881, p<0.001; Se=95%, Sp=76.9%), and with isolated NAFLD (AUC=0.867, p<0.001); Se=76.5%, Sp=81.0%; AUC=0.889, p<0.001, Se=92.3%, Sp=81.3%). IL-10 (AUC=0.769, p=0.012, Se=70%, Sp=64.1%; AUC=0.710, p=0.009, Se=94.4%, Sp=69.2%), IL-1β (AUC=0.752, p=0.02, Se=71.8%, Sp=75.0%; AUC=0.788, p=0.007, Se=84.6%, Sp=66.7%) showed good prognostic characteristics for liver fibrosis progression detection in both groups of patients, and the hsCRP revealed prognostic abilities only in NAFLD and HT patients (AUC=0.849, p<0.001, Se=71,8%; Sp=75.0%). Simultaneous determination of all biomarkers allowed to predict the occurrence and progression of liver fibrosis in NAFLD and HT patients (AUC=1.000, p=0.002, Se=100%, Sp=100%; AUC=0.874, p<0.001, Se=82.1%, Sp=85.0%), and isolated NAFLD patients (AUC=0.874, p<0.001, Se=94.1%, Sp=71.4%, AUC=0.889, p <0.001, Se=84.6%, Sp=94.4%). Conclusions. Kallistatin, IL-10, IL-1β, and hsCRP levels determination can detect liver fibrotic changes in NAFLD and HT patients may be an alternative to invasive diagnostic methods.
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    Diagnostic and Prognostic Potential of Kallistatin in Assessment of Liver Parenchyma Changes in Patients with Non-alcoholic Fatty Liver Disease and Hypertension
    (2021-09) Zhelezniakova, Natalia; Rozhdestvenska, Anastasiia
    Background and Aim. Non-alcoholic fatty liver disease (NAFLD) is closely linked to hypertension (HT). An important issue remains the search for non-invasive tests to NAFLD detection in the early stages of liver fibrosis. The objective of the study was to evaluate the diagnostic and prognostic value of kallistatin in assessing the liver fibrosis progression in NAFLD and HT patients. Patients and Methods. 115 patients with NAFLD with and without HT were examined. Plasma kallistatin level measurement, ultrasound steatometry and elastography were performed in all patients. Results. Kallistatin level was 65.03 ng/ml (95% CI 61.38; 68.68), 83.42 ng/ml (95% CI 81.89; 84.94) and 111.70 (95% CI 106.14; 113.22) in patients with NAFLD and HT, isolated NAFLD and control group, respectively. There were significant differences in the liver parenchyma condition between groups. Kallistatin levels strongly inversely correlated with the attenuation coefficient and the mean liver stiffness in NAFLD and HT (rs=-0.70) and in the isolated NAFLD patients (rs=-0.56; rs=-0.68, respectively). Kallistatin level was 71.82 ng/ml (95% CI 70.16; 79.51) and 58.62 ng/ml (95% CI 55.81; 64.45) in patients with HT stage I and HT stage II, respectively (p<0.001). Conclusions. Concomitant HT in NAFLD patients is associated with greater severity of fatty and fibrotic liver changes. The course of NAFLD is accompanied by decrease in kallistatin level. Increased degree of liver steatosis and fibrosis, inflammation activity, increased BMI and increased stage of HT lead to inhibition of kallistatin activity. Kallistatin can be a biomarker for progression assessment of NAFLD with or without HT.
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    Diagnostic capabilities of kallistatin, IL-10 and IL-1β in patients with non-alcoholic fatty liver disease and hypertension
    (2021-08) Zhelezniakova, Natalia; Rozhdestvenska, Anastasiia
    Introduction. Non-alcoholic fatty liver disease (NAFLD) is closely linked to hypertension (HT) and affects about 25% of the adult population. An important issue remains the search for non-invasive biomarkers for NAFLD diagnosis. The objective of the study was to evaluate the diagnostic value of kallistatin, interleukin-10 (IL-10) and interleukin-1β (IL-1β) in diagnosis of NAFLD in combination with HT. Materials and methods. 115 patients with NAFLD at the stage of non-alcoholic steatohepatitis (NASH) with and without HT were examined. Clinical and laboratory parameters were evaluated; plasma kallistatin, IL-10 and IL-1β levels were measured in all patients. Results. Kallistatin levels averaged 65.03 ng/ml, 83.42 ng/ml and 111.70 ng/ml in patients with NAFLD and HT, isolated NAFLD and control group, respectively. The IL-10 level was 2.69 ng/ml and 4.90 ng/ml in patients with comorbid and isolated NAFLD, respectively, while control results averaged 8.17 ng/ml. The IL-1β level in NAFLD and HT group was 4.76 pg/ml, and in isolated NAFLD group the indicator averaged 4.02 pg/ml, which exceeded the control values (0.59 pg/ml). Conclusions. Concomitant HT in NAFLD patients is associated with significantly more explicit functional liver changes. The course of NAFLD is accompanied by a significant decrease in the plasma kallistatin and IL-10 levels with increase of IL-1β activity. Concomitant HT, higher HT stage and BP grade, increased BMI and high CRP levels are associated with significantly more pronounced biomarker changes. Kallistatin, IL-10 and IL-1β can play an important role in NAFLD diagnosis, in particular, in patients with NAFLD and HT.
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    IL-1β and IL-10: diagnostic and prognostic potential of cytokines in the assessment of progression of non-alcoholic fatty liver disease in patients with hypertension
    (2021-09) Rozhdestvenska, Anastasiia; Zhelezniakova, Natalia
    Introduction. Non-alcoholic fatty liver disease (NAFLD) affects about a quarter of the world's population and is closely linked to hypertension (HT). Pro-inflammatory and anti-inflammatory cytokines play a key role in the pathology progression, and the search for non-invasive biomarkers for the diagnosis of NAFLD remains an important issue. The objective of the study was to determine the diagnostic and prognostic value of IL-1β and IL-10 in assessing the progression of liver parenchyma changes in patients with NAFLD and HT comorbidity. Materials and methods. A study of 115 patients with non-alcoholic steatohepatitis (NASH) was performed. The main group consisted of 63 patients with NASH and HT, 52 patients with isolated NAFLD represented the comparison group. Clinical and laboratory parameters were evaluated, IL-10 and IL-1β levels were measured by ELISA method, ultrasound steatometry and elastography were performed in all patients. Results. The attenuation coefficient and median liver stiffness in NAFLD and HT group significantly exceeded the results in the isolated NAFLD group and in the control group. The IL-1β level in NAFLD and HT group was 4.76 pg/ml, and in isolated NAFLD group the indicator averaged 4.02 pg/ml, which exceeded the control values (0.59 pg/ml). IL-10 level was 2.69 ng/ml and 4.90 ng/ml in patients with comorbid and isolated NAFLD, respectively, while control results averaged 8.17 ng/ml. It were found strong relationship between IL-1β, IL-10 and CRP levels in patients with NAFLD and HT (r = 0.61 and r = -0.69, respectively) Inverse correlations were also found between the cytokines IL-1β and IL-10 in NAFLD patients with and without HT (r = -0.61 and r = -0.57, respectively). Changes in the cytokine status of patients with NAFLD at different stages of steatosis and liver fibrosis have been identified. Conclusions. The presence of concomitant HT in patients with NAFLD is associated with greater severity of liver parenchyma changes. NAFLD manifestation is accompanied by increase of IL-1β and decrease of IL-10 levels, and deepening of these deviations were found in patients with comorbidity of NAFLD and HT. Interleukins IL-1β and IL-10 can be defined as biomarkers of NAFLD progression both in its isolated course and in its comorbidity with HT. The possibility of using biomarkers as an independent non-invasive test of diagnosing NAFLD requires futher study.
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    Non-alcoholic Fatty Liver Disease in Patients with Hypertension: Carbohydrate Metabolism and Liver Parenchyma Condition
    (Metabolism: Clinical and Experimental, 2021-01) Rozhdestvenska, Anastasiia; Zhelezniakova, Natalia; Kurinna, Olena
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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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    Features of the Severity of Cardiovascular Remodeling and Metabolic Disorders in Hypertensive Patients with Obesity in the Presence of Two Unfavorable Genotypes of the ADIPOQ and IRS-1 Genes
    (2020) Shalimova, Anna; Psarova, Valentyna; Kyrychenko, Nataliia; Kochuieva, Maryna
    The results of a number of studies have shown that in ar- terial hypertension (AH), G/T and T/T genotypes of the adiponectin gene (ADIPOQ) and Gly/Arg and Arg/Arg genotypes of the insulin receptor substrate 1 gene (IRS-1) are associated with a greater severity of metabolic disorders and hemodynamic parameters compared with G/G and Gly/ Gly genotypes of these genes. The aim of the study: to evaluate the severity of cardiovas- cular remodeling and metabolic disorders in hypertensive obese patients in the simultaneous presence of two unfa- vorable genotypes of the ADIPOQ and IRS-1 genes.
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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.