Fatty liver disease: heterogeneous phenotype

Relevance. Nonalcoholic fatty liver disease (NAFLD) holds a leading position among the causes of diffuse liver diseases, both in Russia and globally. Moreover, there is a persistent trend of increasing prevalence, especially among patients with metabolic risk factors. The Purpose of the Study: To assess the frequency of detecting fatty liver disease associated with metabolic syndromes in the Republic of Adygea and elucidate the characteristics of disease phenotypes across different age groups. Materials and methods. At stage I, 412 patients aged 18-89 years (45.4% male, 54.6% female) who visited outpatient clinics of therapeutic profile were examined. The average age of the patients was 57.0 ± 15.1 years. At stage II, the study was continued with patients diagnosed with NAFLD. Inclusion criteria for the study were: age 18 years and older, presence of fatty liver disease associated with metabolic conditions. The study continued with 191 patients diagnosed with metabolic associated fatty liver disease (MAFLD) (42.4% male, 57.6% female). The average age of the patients was 60.0 ± 12.4 years. Exclusion criteria from the study were: acute inflammatory diseases or exacerbation of chronic diseases during the study period, presence of viral hepatitis, alcoholic liver disease, autoimmune liver diseases, pregnancy, lactation, and use of medications or narcotics. The diagnosis of fatty liver disease was established in accordance with the recommendations of the Scientific Society of Gastroenterologists of Russia (2021) and the Russian Gastroenterological Association (2022). The diagnosis of metabolic-associated fatty liver disease (MAFLD) was based on visual evidence of hepatic fat accumulation (steatosis) obtained through ultrasonography, accompanied by one of the following criteria: excess body weight or obesity, type 2 diabetes mellitus, and/or signs of metabolic changes, defined as the presence of at least two of the following criteria: MS1 - waist circumference (WC) ≥102 cm in men and ≥88 cm in women; MS2 - body mass index (BMI) ≥25 kg/m²; MS3 - prediabetes (impaired fasting glycemia), homeostatic model assessment of insulin resistance (HOMA-IR) index ≥2.5; MS4 - presence of type 2 diabetes mellitus (T2DM); MS5 - blood pressure ≥130/85 mmHg or the patient receiving specific pharmacological treatment; MS6 (serum C-reactive protein >2 mg/L); MS7 - presence of dyslipidemia or the patient receiving specific pharmacological treatment. Patients were divided into age groups as follows: 18-44 years - young age (Group I); 45-59 years - middle age (Group II); 60-74 years - elderly age (Group III); 75-89 years - old age (Group IV). The study was approved by the Ethics Committee of the Federal State Budgetary Educational Institution “Maykop State Technological University, Medical Institute”. Results. The frequency of detection of fatty liver disease associated with metabolic syndromes in the Republic of Adygea, according to population screening data, was 46.4% (n=191). Out of 191 patients with ultrasound-detected evidence of steatosis, one in every fourth patient (25.1%, n=48) had deviations in liver test parameters from the reference values (laboratory signs of steatohepatitis). There were an average of 4.6±1.0 syndromes per patient in the age group 18-44 years. In the age group of 45-59 years, the average was 4.7 ± 1.1 syndromes, in the age group of 60-74 years, it was 5.0 ± 0.9, and in the age group of 75-89 years, it was 4.8 ± 1.0 syndromes, without statistical differences between the groups. In the age group of 18-44 years, the highest proportion was represented by lipid metabolism disorders (77.8%) and impaired glucose tolerance, HOMA-IR >2.5 (38.9%). In the age groups of 45-59 years and 60-74 years, the highest proportion was represented by type 2 diabetes mellitus (80.3% and 98.9%, respectively) and arterial hypertension (83.6% and 91.6%, respectively). In the age group of 75-89 years, the highest proportion was represented by type 2 diabetes mellitus (100%), elevated levels of serum C-reactive protein (58.8%) (indicating systemic inflammation), and chronic kidney disease (100%). The identified associations suggest the presence of specific age-related disease phenotypes, necessitating an appropriate volume of preventive measures and targeted therapy.

obesity, metabolic associated fatty liver disease, non-alcoholic fatty liver disease, metabolic syndromes, chronic kidney disease, Republic of Adygea

1. Maev I.V., Andreev D. N., Kucheryavyy Yu. A. Metabolically associated fatty liver disease - a disease of the 21st century. Consilium Medicum. 2022;24(5):15-22. (in Russ.) doi: 10.26442/20751753.2022.5.201532.@@ Маев И. В., Андреев Д. Н., Кучерявый Ю. А. Метаболически ассоциированная жировая болезнь печени - заболевание XXI века. Consilium Medicum. 2022;24(5):325-332. doi: 10.26442/20751753.2022.5.201532.

2. Eslam M., Sanyal A. J., George J.; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020 May;158(7):1999-2014.e1. doi: 10.1053/j.gastro.2019.11.312.

3. Lazebnik L. B., Golovanova E. V., Turkina S. V. et al. Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021;1(1):4-52. (in Russ.) doi: 10.31146/1682-8658-ecg-185-1-4-52.@@ Лазебник Л. Б., Голованова Е. В., Туркина С. В. и соавт. Неалкогольная жировая болезнь печени у взрослых: клиника, диагностика, лечение. Рекомендации для терапевтов, третья версия. Экспериментальная и клиническая гастроэнтерология. 2021;1(1):4-52. doi: 10.31146/1682-8658-ecg-185-1-4-52.

4. Ivashkin V. T., Maevskaya M. V., Zharkova M. S. et al. Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(4):104-140. (In Russ.) doi: 10.22416/1382-4376-2022-32-4-104-140.@@ Ивашкин В. Т., Маевская М. В., Жаркова М. С. и соавт. Клинические рекомендации Российского общества по изучению печени, Российской гастроэнтерологической ассоциации, Российской ассоциации эндокринологов, Российской ассоциации геронтологов и гериатров и Национального общества профилактической кардиологии по диагностике и лечению неалкогольной жировой болезни печени. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2022;32(4):104-140. doi: 10.22416/1382-4376-2022-32-4-104-140.

5. Gudinova Zh.V., Demakova L. V. Statistical analysis of medical data: descriptive statistics and group comparison. Fundamental and Clinical Medicine. 2023;8(1):119-131. (In Russ.) doi: 10.23946/2500-0764-2023-8-1-119-131.@@ Гудинова Ж. В., Демакова Л. В. Технологии статистического анализа медицинских данных: первичный анализ данных, сравнение групп. Фундаментальная и клиническая медицина. 2023;8(1):119-131. doi: 10.23946/2500-0764-2023-8-1-119-131.

6. Estes C., Anstee Q. M., Arias-Loste M.T. et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol. 2018 Oct;69(4):896-904. doi: 10.1016/j.jhep.2018.05.036.

7. Evstifeeva S. E., Shalnova S. A., Kutsenko V. A. et al. Prevalence of non-alcoholic fatty liver disease among the working-age population: associations with socio-demographic indicators and behavioral risk factors (ESSE RF-2 data). Cardiovascular Therapy and Prevention. 2022;21(9):3356. (In Russ.) doi: 10.15829/1728-8800-2022-3356.@@ Евстифеева С. Е., Шальнова С. А., Куценко В. А. и соавт. Распространенность неалкогольной жировой болезни печени среди населения трудоспособного возраста: ассоциации с социально-демографическими показателями и поведенческими факторами риска (данные ЭССЕ-РФ-2). Кардиоваскулярная терапия и профилактика. 2022;21(9):3356. doi: 10.15829/1728-8800-2022-3356.

8. Maev I.V., Andreev D. N., Kucheryavyy Yu.A. Prevalence of non-alcoholic fat disease liver in Russian Federation: meta-analysis. Consilium Medicum. 2023;25(5):313-319. (In Russ.) doi: 10.26442/20751753.2023.5.202155.@@ Маев И. В., Андреев Д. Н., Кучерявый Ю. А. Распространенность неалкогольной жировой болезни печени в России: метаанализ. Consilium Medicum. 2023;25(5):313-319. doi: 10.26442/20751753.2023.5.202155.

9. Rietman A., Sluik D., Feskens E. et al. Associations between dietary factors and markers of NAFLD in a general Dutch adult population. Eur J Clin Nutr. 2018 Jan;72(1):117-123. doi: 10.1038/ejcn.2017.148.

10. Vilar-Gomez E., Nephew L. D., Vuppalanchi R. et al. High-quality diet, physical activity, and college education are associated with low risk of NAFLD among the US population. Hepatology. 2022 Jun;75(6):1491-1506. doi: 10.1002/hep.32207.

11. De Lucia Rolfe E., Brage S., Sleigh A. et al. Validity of ultrasonography to assess hepatic steatosis compared to magnetic resonance spectroscopy as a criterion method in older adults. PLoS One. 2018 Nov 26;13(11): e0207923. doi: 10.1371/journal.pone.0207923.

12. Chalasani N., Younossi Z., Lavine J. E. et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367.

13. Noubiap J.J., Nansseu J. R., Lontchi-Yimagou E. et al. Geographic distribution of metabolic syndrome and its components in the general adult population: A meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022 Jun;188:109924. doi: 10.1016/j.diabres.2022.109924.

14. Drapkina O.M., Ivashkin V. T. Epidemiologic features of non-alcoholic fatty liver disease in Russia.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2014;24(4):32-38. (In Russ.)@@ Драпкина О. М., Ивашкин В. Т. Эпидемиологические особенности неалкогольной жировой болезни печени в России. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2014;24(4):32-38.

15. Radu F., Potcovaru C. G., Salmen T., Filip P. V., Pop C., Fierbințeanu-Braticievici C. The Link between NAFLD and Metabolic Syndrome. Diagnostics (Basel). 2023 Feb 7;13(4):614. doi: 10.3390/diagnostics13040614.

16. Mazloomzadeh S., Karami Zarandi F., Shoghli A., Dinmohammadi H. Metabolic syndrome, its components and mortality: A population-based study. Med J Islam Repub Iran. 2019 Feb 27;33:11. doi: 10.34171/mjiri.33.11.

17. Krasner Ya.A., Osipenko M. F., Holin S. I., Litvinova N. V. Chronic kidney disease and non-alcoholic fatty liver disease - new pathogenetic links. Experimental and Clinical Gastroenterology. 2023;(4):140-144. (In Russ.) doi: 10.31146/1682-8658-ecg-212-4-140-144.@@ Краснер Я. А., Осипенко М. Ф., Холин С. И., Литвинова Н. В. Хроническая болезнь почек и неалкогольная жировая болезнь печени - новые патогенетические взаимосвязи. Экспериментальная и клиническая гастроэнтерология. 2023;(4):140-144. doi: 10.31146/1682-8658-ecg-212-4-140-144.