Наукові праці. Кафедра внутрішньої медицини № 1

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    The role of insulin resistance in the development of metabolic dysfunction-associated steatotic liver disease and arterial hypertension
    (ГО “Наукова спільнота”, WSZIA w Opolu, 2025) Zhelezniakova, Natalia; Aleksandrova, Tetiana; Molodan, Volodymyr; Panchenko, Galyna
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    Therapeutic potential of sodium selenite in patients with non-alcoholic fatty liver disease and hypertension disease
    (2023-06) Tverezovska, Iryna; Zhelezniakova, Natalia
    Liver 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 direction
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    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, Iryna
    Objective. 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.
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    Morphological peculiarities of cerebral injury in polyomavirus infection in HIV-positive individuals
    (2022) Zhelezniakova, Natalia; Bondarenko, A.; Katsapov, D.; Pasiieshvili, Tamara; Bocharova, Tetiana; Gargin, Vitaliy
    The article presents information about the study of morphological features in progressive multifocal leukoencephalopathy caused by polyomavirus infection in HIV-infected individuals. A study of sectional material (the brain) was carried out. After routine proceeding and histological staining, the slides were studied under Olympus BX41 microscope, followed by a morphometric examination. According to neuroimaging methods, the presence of multiple foci in the brain may be caused by the presence of several etiological factors: JCV, BKV, EBV, T. gondii, and C. neoformans, which requires mandatory laboratory confirmation. Morphological changes in the brain in PML caused by JCV and BKV are characterized by areas of demyelinated lesions 2-3 mm in size with a tendency to merge, with significant areas of white matter affected and degenerative changes predominantly in the juxtacortical/subcortical white matter.
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    Morphological peculiarities of cerebral injury in polyomavirus infection in HIV-positive individuals
    (2022) Zhelezniakova, Natalia; Bondarenko, A.; Katsapov, D.; Pasiieshvili, Tamara; Bocharova, Tetiana; Gargin, Vitaliy
    The article presents information about the study of morphological features in progressive multifocal leukoencephalopathy caused by polyomavirus infection in HIV-infected individuals. A study of sectional material (the brain) was carried out. After routine proceeding and histological staining, the slides were studied under Olympus BX41 microscope, followed by a morphometric examination. According to neuroimaging methods, the presence of multiple foci in the brain may be caused by the presence of several etiological factors: JCV, BKV, EBV, T. gondii, and C. neoformans, which requires mandatory laboratory confirmation. Morphological changes in the brain in PML caused by JCV and BKV are characterized by areas of demyelinated lesions 2-3 mm in size with a tendency to merge, with significant areas of white matter affected and degenerative changes predominantly in the juxtacortical/subcortical white matter.
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    Pathomorphological features of gastroesophageal reflux disease realization in young people with autoimmune thyroiditis
    (2022-02) Pasiieshvili, Tamara; Bocharova, Tetiana; Zhelezniakova, Natalia; Pasiieshvili, Liudmyla
    The aim: To evaluate the pathomorphological features of the esophageal mucous membrane in young people with GERD and autoimmune thyroiditis. Materials and methods: 120 patients with GERD and AIT and 45 people with isolated GERD matched for age, gender and social status were examined. Esophagogastroduodenoscopy, histological study and comparative morphometry of the esophageal mucosa were performed. Results: The frequency of erosive GERD in the examined groups of patients did not statistically differ. At the same time, integral analysis of the structure of erosive forms of GERD revealed statistically significant redistribution of grades of esophagitis towards its enhancement in patients with comorbid pathology. The histological study showed that in patients with GERD and AIT all the morphometric parameters studied had a significantly more severe course and exceeded similar indicators of the group with isolated GERD: epithelium total thickness, epithelium basal layer thickness, connective tissue papillae height, intercellular space. The analysis of morphological changes frequency showed that epithelium basal layer hyperplasia, dystrophic changes and epithelial edema, elongation of papillae and dilation of intercellular space were significantly more frequent in the group with comorbid pathology. Conclusions: GERD and euthyroid AIT comorbidity in the student population is accompanied by a statistically significant redistribution of esophagitis grades towards its aggravation. The presence of concomitant euthyroid AIT in patients with non-erosive GERD leads to statistically more pronounced disorganization of esophageal mucosal epithelium.
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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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    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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    Morphometric parameters of esophageal mucous in young people with gastroesophageal reflux disease and autoimmune thyroiditis
    (2022) Zhelezniakova, Natalia; Gargin, Vitaliy; Bocharova, Tetiana; Pasiieshvili, Tamara; Pasiieshvili, Liudmyla
    Background & objectives: Gastroesophageal reflux disease (GERD) takes one of the leading positions in internal organs` pathology with comorbidity. Objective of our work was evaluation of morphometric parameters of the esophageal mucous membrane in young people with GERD and autoimmune thyroiditis (AIT). Methods: Patients with GERD and AIT (main group) and 45 people with isolated GERD (comparison group) matched for age, gender, and social status were examined. The mean age in the groups was 21.9 ± 2.7 and 21.2 ± 2.4 years. Morphometric parameters were obtained (total thickness of the epithelium, basal layer thickness, the height of connective tissue papillae, and intercellular space). Results: The histological study showed that in patients with GERD and AIT all the morphometric parameters studied had a significantly more severe course and exceeded similar indicators of the group with isolated GERD: epithelium total thickness 319.3±9.1 μm against 286.1±8.2 μm (p<0.01), epithelium basal layer thickness 79.6±3.2 μm versus 49.7±2.1 μm (p<0.01), connective tissue papillae height 224.8±7.3 μm against 172.7±4.6 μm (p<0.01), intercellular space 1.55±0.11 μm versus 1.12±0.09 μm (p<0.01). Considerable aggravation of the deviations in patients with AIT may reflect the involvement of an additional autoimmune inflammatory component in the pathological process. Conclusion: GERD and euthyroid AIT comorbidity in the student population is accompanied by statistically more pronounced disorganization of esophageal mucosal epithelium compared with isolated GERD. The obtained data allow us to consider concomitant AIT as an unfavorable prognostic factor in the progression of GERD in the student population.
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    Anti-inflammatory and pro-inflammatory biomarkers in patients with non-alcoholic fatty Liver disease and hypertension
    (2022) Rozhdestvenska, Anastasiia; Zhelezniakova, Natalia
    Introduction. 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.