Наукові праці. Кафедра внутрішньої медицини № 1
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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 Kallistatin as a biomarker of non-alcoholic fatty liver disease progression in patients with hypertension(2021-10) Rozhdestvenska, Anastasiia; Zhelezniakova, NataliaBackground and Aims: The prevalence of nonalcoholic fatty liver disease (NAFLD) ranges from 17% to 46% worldwide. Searching for non-invasive diagnostic methods of the NAFLD severity and progression becomes a central objective, especially, in patients with combination of NAFLD and arterial hypertension (HT). Kallistatin is an tissue kallikrein inhibitor, endogenous protein, which is predicted to play an important role in anti-inflammatory protection and prevention of the chronic liver diseases progression. The aim of the study was to determine the role of kallistatin as a diagnostic biomarker of NAFLD progression in patients with concomitant HT. Matherials and methods: We examined 115 patients with NAFLD in non-alcoholic steatohepatitis (NASH) stage. They were divided into two groups: the main group consisted of 63 patients with NAFLD on the background of HT and the comparison group consisted of 52 patients with isolated NAFLD. The control group was composed of 20 relatively healthy volunteers. Anthropometric parameters were obtained using standard methods. Plasma kallistatin levels were measured using the Human SERPINA4 (Kallistatin) ELISA Kit (Elabscience, USA). The level of C-reactive protein (CRP) was determined using the hs-CRP ELISA Kit (Biomerica USA). The data was statistically processed using standart PC-programmes. Results: The kallistatin level in patients with comorbidity of NAFLD and HT averaged 65.98 ng/ml (95% CI 62.85; 69.12), that was less, than in group of isolated NAFLD (83.42 ng/ml (95% CI 81.89; 84.94)) and control group (111.70 ng/ml (95% CI 106.14; 113.22)) in 1.3 (p < 0.001) and 1.7 times (p < 0.001), respectively. The levels of kallistatin were decreased in patients on condition of increasing body mass index (BMI) both in the group with NAFLD and HT and in the group with isolated NAFLD (r = -0.58, p < 0.001; r = 0.54, p = 0.002, respectively). The content of kallistatin decreased with the progression of HT in patients from the main group: in patients with HT I stage the level of biomarker averaged 73,38 ng/ml (95% ДІ 70,24; 78,19) while in patients with HT II stage its values were 61,87 ng/ml (95% ДІ 58,12; 65,62), p < 0.001. At the same time, the biomarker levels were significantly different in patients with HT II, depending on hypertension grade and declined with increase of blood pressure (BP) numbers. The highest CRP value was found in the NAFLD and HT group (7.90 mg/l (95% CI 7.96; 8.75)) versus 6.55 mg/l (95% CI 6.47; 7.57) and 2.07 mg/l (95% CI 1.83; 2.85) in the isolated NAFLD group and control results, respectively. The correlations between kallistatin and CRP were signed as very strong (r = -0.89) and strong (r = -0.61) in group with comorbidity of NAFLD and HT and in patients with isolated NAFLD, respectively. Conclusions: We founded the significant decrease in the content of kallistatin in plasma of patients with NAFLD. It was proven that concomitant HT, stage of target organs injury, higher BP grade, as well as increased BMI and CRP levels are associated with significantly more pronounced deviations of this biomarker. This data provide the possibility to consider kallistatin as a biomarker of NAFLD progression, in particular, in patients with NAFLD and HT.Item Non-alcoholic fatty disease and hypertension: virtual presentations of comorbid pathology(2021) Rozhdestvenska, Anastasiia; Zhelezniakova, NataliaItem 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.Item 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, NataliaIntroduction. 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.Item 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, OlenaItem Non-alcoholic fatty liver disease and hypertension: clinical variability of comorbidity(2020-11) Рождественська, Анастасія Олександрівна; Железнякова, Наталя Мерабівна; Rozhdestvenska, Anastasiia; Babak, Oleg; Zhelezniakova, NataliaIntroduction. 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.