Наукові праці. Кафедра внутрішньої медицини № 1
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Item Therapeutic potential of sodium selenite in patients with non-alcoholic fatty liver disease and hypertension disease(2023-06) Tverezovska, Iryna; Zhelezniakova, NataliaLiver parenchyma damage is associated with significant activation of oxidative stress. Correction of oxidative stress can be a promising direction in the treatment of arterial hypertension. It has been established that in patients with hepatopathies, lower concentrations of selenium are found in blood and erythrocytes, which gives reason to consider selenium as a potential therapeutic agent in patients with liver pathology.Objective — to determine the therapeutic potential of sodium selenite in patients with non-alcoholic fatty liver disease in combination with hypertension.Materials and methods. 100 patients with nonalcoholic fatty liver disease (NAFLD) were included in the study: the main group — 49 patients (67.3 % women, median age is 51.0 years) with concomitant NAFLD and arterial hypertension (HTN), the comparison group — 51 patients (58.8 % women, median age is 52.0 years) with NAFLD isolated course. The control group included 20 practically healthy people (55.0 % women, median age is 51.0 years). Among the patients of the main group, the first degree of HTN was diagnosed in 28.6 % of patients (14 people), the second degree — 71.4 % (35 people). Among these patients, 32.7 % (16 people) had the first stage of HTN, 67.3 % (33 people) had the second stage. In the main group, 55.1 % of patients had steatosis, 44.9 % had steatohepatitis. In the comparison group, 58.8 % had steatosis, 41.2 % had steatohepatitis (2 = 0.141, p= 0.707). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured according to the standard method (kinetic method). Gamma-glutamine transpeptidase (GGTP) was measured by the enzy-matic colorimetric method, alkaline phosphatase (AP) by the colorimetric method. Selenium and selenoprotein P (Sel P) levels were determined using the immunofluorescence method. Ultrasound examination of the liver was performed according to the standard method on an empty stomach.Results. Body mass index corresponded to normal or increased body weight: in the main group — 27.8 [26.6; 28.5] kg/ m2 and 27.3 [24.2; 28.3] kg/ m2 in the comparison group, in the control group — 24.3 [21.9; 26.0] kg/ m2. In patients of the main group was determined a significant (p < 0.001) predominance of ALT levels (45 [43.0; 47.5] U/ L), AST levels (53 [51.0; 56.0] U/ L), AP levels (285.7 [217.6; 321.1] U/ L) and GGTP levels (96.2 [75.0; 108.9] U/ L) opposite to comparison group (respectively 36 [34.0; 39.0] U/ L, 41 [40.0; 45.0] U/ L, 215.5 [183.2; 246.7] U/ L and 65.5 [51.5; 76.8] U/ L) and control group levels (respectively 25.5 [24.0; 30.8] U/ L, 23 [19.3; 26.0] U/ L, 129.2 [116.9; 140.6] U/ L and 22.6 [16.1; 31.7] U/ L). A two-fold decrease in selenoprotein P levels was obtained in patients with NAFLD and HTN compared to patients with NAFLD (19.7 [8.0; 26.7] ng/ mL and 43.1 [41.3; 45.4] ng/ mL respectively, p < 0.001), and selenium in one and a half times compared to patients with NAFLD (43.5 [39.9; 49.1] g/ L and 67.2 [61.5; 77.4] g/ L respectively, p < 0.001). The highest Sel P median levels (71.0 [54.3; 76.1] ng/ ml and selenium levels (108.0 [96.9; 118.8] g/ L) registered in the control group (p < 0.001). Evaluating the data on selenium metabolism and liver tests depending on the intake of sodium selenite, a significant increase in the levels of Sel P (53.6 [43.1; 60.4] ng/ ml, p < 0.001) and selenium (89.1 [63, 4; 99.5] g/ L, p < 0.009), as well as a decrease in AST levels (41.7 [32.6; 43.2] U/ l, p < 0.001) in the group with isolated NAFLD, while in the group with NAFLD and HTN comorbid course, no significant changes in the studied parameters were detected.Conclusions. The obtained results provide a basis for sodium selenite use in the therapy of patients with NAFLD. Further research on the duration of such therapy and sodium selenite dosing regimen in patients with a comorbid course of NAFLD and HTN is a promising and relevant directionItem 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, AnnaBackground: 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.Item Comparison of structural and functional vascular disorders in patients with comorbidity of non-alcoholic fatty liver disease and two types of arterial hypertension(2023) Prosolenko, Kostyantyn; Molodan, Volodymyr; Panchenko, Galyna; Lapshyna, Kateryna; Shalimova, AnnaBackground: 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.Item Comparison of structural and functional vascular disorders in patients with comorbidity of non-alcoholic fatty liver disease and two types of arterial hypertension(2023) Prosolenko, Kostyantyn; Molodan, Volodymyr; Panchenko, Galyna; Lapshyna, Kateryna; Shalimova, AnnaBackground: 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. Key words: structural and functional vascular alterations; non-alcoholic fatty liver disease; hypertensionItem Diagnostic and prognostic value of selenium and selenoprotein P in patients with comorbid course of non-alcoholic fatty liver disease and arterial hypertension(2022) Zhelezniakova, Natalia; Tverezovska, IrynaObjective. To evaluate the diagnostic and prognostic value of Selenoprotein P and selenium in the progression of liver damage in patients with nonalcoholic fatty liver disease (NAFLD). Methods. The study involved 120 patients: 50 with isolated NAFLD, 50 - with comorbid NAFLD and hypertension, established according to the world and local guidelines. Control group included 20 relatively healthy volunteers. Liver function parameters, selenium and Selenoprotein P levels were assessed, and predictors of steatohepatitis were identified. Pearson's χ2, Mann-Whitney test, logistic regression were used. Results. The study found significant predominance of levels of Selenoprotein P (Sel P) and selenium in controls (71.0 [54.3; 76.1] ng/ml and 108.0 [96.9; 118.8] ng/ml respectively) compared with the NAFLD + hypertension (19.7 [8.0; 26.7] ng/ml and 43.5 (39.9; 49.1] ng/ml, p <0.001) and the NAFLD group (43.1 [41.3; 45.4] ng/ml and 67.2 [61.5; 77.4] ng/ml, respectively, p <0.001). Regression analysis determined association of Sel P and Sel levels with steatohepatitis: respectively, OR = 1,143 [95.0% CI 1,068–1,224] (p <0.001) and OR = 1,054 [95.0% CI 1,012–1,098] (p = 0.011). Other predictors of steatohepatitis were aspartateaminotransferase (OR = 1,421 [95.0% CI 1,198–1,687], p <0.001) and systolic blood pressure (OR = 1,089 [95.0% CI 1,017–1,116], p = 0.014). Conclusions. Levels of selenium and Selenoprotein P are associated with greater liver damage in patients with NAFLD, and the concomitant increase in systemic blood pressure is an additional factor that adversely affects the course of NAFLD, increasing the intensity of liver damage in such patients.Item Kallistatin, IL-10, IL-1β and hsCRP in the diagnosis of non-alcoholic fatty disease on the background of hypertension(2022) Rozhdestvenska, Anastasiia; Zhelezniakova, NataliaBackground: 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.Item Anti-inflammatory and pro-inflammatory biomarkers in patients with non-alcoholic fatty Liver disease and hypertension(2022) Rozhdestvenska, Anastasiia; Zhelezniakova, NataliaIntroduction. Non-alcoholic fatty liver disease (NAFLD) affects up to 50% of patients with hypertension (HT). Research data indicate a decrease in the activity of anti-inflammatory biomarkers with a simultaneous increase in the levels of pro-inflammatory agents. Objective. To assess the changes in anti-inflammatory systems (using kallistatin, IL-10) and proinflammatory activity (using IL-1β; and high-sensitivity CRP (hsCRP)) in patients with NAFLD under the influence of concomitant HT. Design and method. 63 patients with NASH and HT and 52 patients with isolated NASH were examined. Plasma kallistatin, IL-10, IL-1β; and hsCRP levels were evaluate using ELISA. The results were statistically processed using standard methods. Results. Kallistatin levels in patients with NAFLD and HT were on average 65.03 ng/ml (95% CI 61.38; 68.68), which was significantly lower than in the group with isolated NAFLD (83.42 ng/ml (95% CI 81.89; 84.94), p<0.001) and control results (111.70 ng/ml (95% CI 106.14; 113.22), p<0.001). The level of anti-inflammatory IL-10 in the group of NAFLD and HT also reached minimal values (12.69 pg/ml (95% CI 11.93; 12.95) against 14.34 pg/ml (95% CI 13.27; 14,34) in the group with isolated NAFLD (p<0.001) and 16.19 pg/ml (95% CI 15.15; 17.74) in the control group (p<0.001)). The opposite results were observed in the study of IL-1β; content, which was increased in the group with NAFLD and HT (17.55 pg/ml (95% CI 17.06; 19.73) versus 15.72 pg/ml (95% CI 15,25; 17.44) in the group with isolated NAFLD (p<0.001) and 8.26 (95% CI 7.79; 8.46) in the control group (p<0.001)). In addition, patients with NAFLD and HT had an increase in CRP (7.90 mg/l (95% CI 7.96; 8.75) versus 6.55 mg/l (95% CI 6.47; 7.57) in the group with isolated NAFLD (p<0.001) and 2.07 mg/l (95% CI 1.83; 2.85 mg/l) in the control group (p<0.001)). It has been shown that with the progression of HT in patients with NAFLD, the level of kallistatin significantly decreases (p<0.001, p=0.011 for the HT stage and BP grade) and IL-10 (p<0.001) with a simultaneous increase in IL-1β; (p<0.001) and CRP levels (p<0.001). Conclusions. Thus, patients with NAFLD and HT are likely to experience changes in biomarker status toward a pro-inflammatory profile and deepening of these deviations with the progression of concomitant hypertension.Item Hypertension as an intensification factor of metabolic and inflammatory deviations in patients with non-alcoholic fatty liver disease(2021-07) Zhelezniakova, Natalia; Rozhdestvenska, AnastasiiaItem 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, AnastasiiaBackground 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.Item Diagnostic capabilities of kallistatin, IL-10 and IL-1β in patients with non-alcoholic fatty liver disease and hypertension(2021-08) Zhelezniakova, Natalia; Rozhdestvenska, AnastasiiaIntroduction. 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.