Tverezovska I. The role of selenoprotein P in optimizing the diagnosis, treatment and prognosis of the course of non-alcoholic fatty liver disease against the background of hypertension

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0823U101695

Thesis Registration Form

0823U101695.pdf

Applicant for

Specialization

  • 222 - Медицина

Specialized Academic Board

СВР 29_3423

Kharkiv National Medical University

Essay

Nonalcoholic fatty liver disease (NAFLD) is a collective concept and includes a number of pathological conditions from steatosis and nonalcoholic steatohepatitis to cirrhosis and hepatocellular carcinoma. Since the selenium-deficient state is associated with inhibition of antioxidant protection, determining the concentration of selenium metabolism indicators, as well as adding selenium-containing compounds to diagnosis and treatment algorithms of patients with NAFLD is a promising direction. Therefore, the goal of our work was to optimize the diagnosis, treatment and prognosis of non-alcoholic fatty liver disease course in the comorbid course with arterial hypertension based on the determination of the pathogenetic significance and prognostic potential of cytokine status indicators and parameters of selenium metabolism. One hundred patients were included in the study: 49 of the main group had a concomitant course of NAFLD and hypertension (HTN), and 51 patients of the comparison group had an isolated course of NAFLD. The control group consisted of 20 relatively healthy people. In terms of gender distribution, the groups were comparable (p = 0.544), the proportion of women prevailed in all groups: 67.3% in the main group, 58.8% in the comparison group, and 55% in the control group. Patients were comparable in age (p > 0.05): the median age of the main group was 51.0 [45.0; 56.0] years; of the comparison group —52.0 [47.0; 54.0] years and of the control group — 51.0 [45.0; 55.0] years old. Among the main group, liver steatosis was established in 27 patients (55.1%), steatohepatitis in 22 patients (44.9%); in the comparison group there were 30 patients (58.8%) and 21 patients (41.2%), respectively (χ2 = 0.141, p1-2 = 0.707). There were 14 (28.6%) patients of the main group who had the 1st degree of arterial hypertension, the 2nd degree – 35 (71.4%) (р< 0.001, χ2 = 100.00). Among them, 16 people (32.7%) had stage 1 arterial hypertension, 33 (67.3%) stage 2, respectively (р< 0.001, χ2 = 100.00). The diagnosis of NAFLD and HTN was established at the preliminary stages of applying to medical and preventive institutions, taking into account local and European recommendations All respondents were collected complaints, medical history, life history, anthropometric parameters were measured, clinical blood analysis, biochemical indicators of liver function (AST, ALT, GGTP, ALP, total bilirubin), lipid profile (TC, TAG, HDL, LDL, VLDL, atherogenic coefficient), glucose levels, serum levels of selenoprotein P and selenium, interleukin-8, interleukin-10 determined by immunofluorescence analysis (ELISA Kit ). As well as the risks of steatosis and liver fibrosis were calculated according to the FLI index, the NAFLD Score and FIB-4 scales, the APRI index. ECG and ultrasound of the abdominal organs were performed. It was determined that selenoprotein P and selenium median levels were significantly reduced in patients of the NAFLD+HTN group, compared to the control group. The highest concentration of ALT, AST, GGTP, ALP and IL-8, IL-10 was in the patients of the NAFLD+HTN group. Correlation analysis confirmed the existence of a relationship between selenium metabolism, liver enzymatic activity and anti-inflammatory homeostasis: in patients of the NAFLD+HTN group, a direct correlation was found between the levels of Sel P and selenium, between Sel P and AST, between Sel P and IL-10, between selenium and ALT. A similar trend was noted in the group with an isolated course of NAFLD. After completing the course of treatment, a significant doubling of the median levels of selenoprotein P and selenium, as well as a decrease in the levels of AST, GGTP, ALP, IL-8 and IL-10 was obtained in patients with NAFLD and HTN. Against the background of selenium supplementation, a significant increase in the content of selenoprotein P and selenium, a decrease in AST was obtained in patients with an isolated course of NAFLD. Prognostic models were developed: a model for the development of steatohepatitis in patients with NAFLD, models for the development of HTN in patients with NAFLD, and a model for the development of NAFLD in healthy individuals.

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Research papers

1. Iryna I. Tverezovska, Natalia M. Zhelezniakova. The relationship of selenium metabolism with inflammatory activity of the liver in patients with non-alcoholic fatty liver disease and hypertension disease. Wiadomości Lekarski – 2022. – Vol. LXXV, Issue 11, Part 1. – P. 2671-2676.

2. Natalia M. Zhelezniakova, Iryna I. Tverezovska. Diagnostic and prognostic value of Selenium and Selenoprotein P in patients with comorbid course of non-alcoholic fatty liver disease and hypertension. / I.I. Tverezovska, N.M. Zhelezniakova // Medicinski časopis. – 2022. – Vol. 56, Issue 2. – P. 68-76.

3. Тверезовська І. І., Железнякова Н. М. Цитокінзалежні механізми реалізації імунної відповіді у пацієнтів з неалкогольною жировою хворобою печінки та гіпертонічною хворобою / І.І. Тверезовська, Н.М. Железнякова // Сучасна гастроентерологія.— 2022.— №5—6.— C.24—31.

4. Тверезовська І.І. Цитокіновий дисбаланс та прогресування змін паренхіми печінки у пацієнтів з неалкогольною жировою хворобою печінки та гіпертонічною хворобою. / І.І. Тверезовська, Н.М. Железнякова // Український терапевтичний журнал. — 2023. — №1. — С. 22-30.

5. Tverezovska I.I., Zhelezniakova N.M. Therapeutic potential of sodium selenite in patients with non-alcoholic fatty liver disease and hypertension disease. / I.I. Tverezovska, N.M. Zhelezniakova // Сучасна гастроентерологія. — 2023. — №3. — Р. 20-28.

6. Tverezovska, I. I., Zhelezniakova N. M. Selenoprotein P as a Marker of Comorbid Development of Nonalcoholic Fatty Liver Disease and Hypertension. / I.I. Tverezovska, N.M. Zhelezniakova // Metabolism. – March, 2021– Vol. 116, Suppl. 154680.

7. Тверезовська І.І., Железнякова Н.М. Роль селенопротеїну P в оптимізації діагностики та прогнозування перебігу неалкогольної жирової хвороби печінки. / І.І. Тверезовська, Н.М. Железнякова //Збірник матеріалів науково-практичної конференції з міжнародною участю «Young Science 3.0» (26 березня 2021 року, м. Київ) – Київ, 2021. – С.126–127.

8. Тверезовська І.І., Железнякова Н.М. Неалкогольна жирова хвороба печінки як обтяжуючий фактор розвитку серцево-судинної патології. / І.І. Тверезовська, Н.М. Железнякова // Матеріали ХVIІI Наукової конференції студентів та молодих вчених «Перший крок в науку — 2021» (15-17 квітня, м. Вінниця). – Вінниця, 2021. – С. 557.

9. Tverezovska, I. I., Zhelezniakova, N. M. Clinical significance of the AST to Platelet ratio index in patients with non-alcoholic fatty liver disease and hypertension. / І.І. Tverezovska, N.M. Zhelezniakova // Journal of the Hong Kong College of Cardiology, 2022. – Vol. 28, Issue 3. – P. 32.

10. Tverezovska I. I., Zhelezniakova N. M. Correlations of IL-10 and selenoprotein-P in hypertensive and non-hypertensive NAFLD patients with different grade of live damage. / І.І. Tverezovska, N.M. Zhelezniakova // Materials of the Maltepe University International Student Congress «Human and health in the evolving world» (MUISC 21-22), 12-13 of May, Istambul, Turkey). – Turkey, 2022. – P. 57.

11. Natalia M. Zhelezniakova, Iryna I. Tverezovska. Relationships of pro-, anti-inflammatory markers and levels of selenoprotein P and selenium with liver damage grade in patients with nonalcoholic fatty liver disease. / І.І. Tverezovska, N.M. Zhelezniakova // Wiadomości Lekarski. – May, 2022. – Vol. LXXV, Issue 5, Part 1. – P. 1215.

12. Iryna Tverezovska, Natalia Zhelezniakova. Активність показників функціонального стану печінки у пацієнтів з неалкогольною жировою хворобою печінки на тлі гіпертонічної хвороби/ Тверезовська І.І., Железнякова Н.М. //Збірник матеріалів науково-практичної конференції з міжнародною участю «Young Science 4.0» (30 травня 2022 року, м. Київ) – Київ, 2022. – С. 114-115.

13. Tverezovska, I. I., Zhelezniakova, N. M. Selenium metabolism and systemic inflammation in hypertensive patients with nonalcoholic fatty liver disease. / Tverezovska, I. I., Zhelezniakova, N. M. // American Heart Journal. – USA, 2022. – Volume 254. – P. 252

14. Iryna Tverezovska, Natalia Zhelezniakova. Predictors of steatohepatitis in hypertensive nonalcoholic fatty liver disease patients. / Tverezovska, I. I., Zhelezniakova, N. M. // Abstract Book of EASL NAFLD Summit 2022, Dublin, Ireland (September 15-17, 2022). – 2022. – P. 106-107

15. Тверезовська І.І., Железнякова Н.М. Зв’язок показників обміну селену та протизапальної відповіді у пацієнтів з гіпертонічною хворобою та неалкогольною жировою хворобою печінки. / Тверезовська І.І., Железнякова Н.М. // Український кардіологічний журнал. Матеріали XXIІІ Національного конгресу кардіологів України (20 — 23 вересня 2022, м. Київ), — Київ, 2022. — Том. 29, Додаток 1. — С. 82.

16. Iryna Tverezovska, Natalia Zhelezniakova. Selenium levels and functional state of liver in patients with hypertension and nonalcoholic fatty liver disease. / Tverezovska, I. I., Zhelezniakova, N. M. // Abstract book of 29th Scientific Meeting of the International Society of Hypertension (ISH2022) 12-16 October, 2022, Kyoto, Japan, — Japan, 2022. — P. 55

17. Iryna I. Tverezovska, Natalia M. Zhelezniakova. Relationships of pro-, anti-inflammatory markers and levels of selenoprotein P and selenium with liver damage grade in patients with nonalcoholic fatty liver disease. / Tverezovska I. I., Zhelezniakova N. M //Wiadomości Lekarski. – November, 2022. – Vol. LXXV, Issue 11, Part 1. – P. 2707

18. I. I. Tverezovska, N. M. Zhelezniakova. Association of liver enzymes and selenium metabolism in patients with non-alcoholic fatty liver disease depending on the functional state of the liver. / Tverezovska I. I., Zhelezniakova N. M // Тези за матеріалами: ХVI Всеукраїнської науково-практичної конференції молодих вчених «Актуальні питання клінічної медицини» (24-25 листопада 2022 р., м. Запоріжжя). – Запоріжжя, 2022. – С. 263-264

19. Tverezovska Iryna, Rozhdestvenska Anastasiia. Lipid metabolism and steatohepatitis development in patients with nonalcoholic fatty liver disease and arterial hypertension. / І.І. Тверезовська, А.О. Рождественська// Медицина третього тисячоліття: Збірник тез міжвузівської конференції молодих вчених та студентів (13 – 15 лютого 2023, м. Харків), – Харків, 2023.– P. 69–71.

20. Tverezovska I., Zhelezniakova N. Selenium use potency in the treatment of patients with non-alcoholic fatty liver disease and concomitatnt arterial hypertension. / Tverezovska, I., Zhelezniakova N. // 1st International Conference on Frontiers in Academic Research ICFAR 2023 (February 18-21, 2023). – Turkey: Konya, 2023. – Vol. 1. – Р. 222-223.

21. I. Tverezovska, N. Zhelezniakova. Lipid fractions changes in predicting the development of nonalcoholic fatty liver disease. / Tverezovska, I., Zhelezniakova N. // Atherosclerosis. Abstract book of 91st EAS Congress, Mannheim, Germany (May 21-23, 2023). – August, 2023. – V. 379, Suppl. 1, S78. – P.246.

22. Тверезовська І.І., Железнякова Н.М. Дисбаланс селену як прогностичний маркер прогресування артеріальної гіпертензії в пацієнтів із неалкогольною жировою хворобою печінки / Тверезовська І.І., Железнякова Н.М. // Український кардіологічний журнал. Матеріали XXIV Національного конгресу кардіологів України (19 — 22 вересня 2023, м. Київ), — Київ, 2023. — Том. 30, Додаток 1. — С. 97.

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