Clinical-nutritional and metabolic disorders in the formation of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a range of diseases, including non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), potentially leading to cirrhosis and hepatocellular carcinoma. Globally, approximately 30% of the population suffers from NAFLD, with recent data indicating an increasing prevalence. The increasing incidence of NAFLD and its complex relationship with metabolic dysfunction highlight the risk of liver cirrhosis in patients with different BMIs who are not provided with timely diagnosis and therapy. Therefore, it is critical to prioritize prevention and screening measures for NAFLD. The purpose of our work was to determine risk factors for the development of NAFLD with and without obesity. Materials and methods. A one-time study was carried out with a comprehensive assessment of nutritional status, including anthropometry, bioimpedansometry and assessment of actual nutrition, as well as a study of the level of biochemical and hormonal indicators on the basis of the Regional Clinical Hospital of War Veterans No. 3 in Novosibirsk. A total of 349 people took part in the study. Of these: 113 patients with NAFLD without obesity, 122 patients with NAFLD with obesity according to BMI and 114 apparently healthy people. Results and its discussion. In the course of multivariate regression analysis, models were identified that combine a set of factors influencing the development of non-alcoholic fatty liver disease in patients with different nutritional status. For patients with NAFLD without obesity, the factors for the development of the disease are: excess dietary cholesterol intake EXP(B) = 1.004 95CI [1.001-1.008], HOMA -IR index EXP(B) = 20.535 95CI [5.893-71.551], total cholesterol level EXP (B) = 5.092 95CI [2.226-11.649], gamma-glutamyl transpeptidase (GGTP) EXP(B) = 1.282 95CI [1.155-1.423] and visfatin EXP(B) = 1.117 95CI [1.067-1.107]. In patients with NAFLD in combination with obesity, the risk factor model consisted of total fat mass according to bioimpedance measurements EXP(B) = 1.288 95CI [1.123-1.477], HOMA-IR index EXP(B) = 13.318 95CI [3.045-58.242], level GGT EXP(B) = 1.388 95CI [1.185-1.626] and visfatin EXP(B) = 1.193 95CI [1.063-1.338]. Conclusion. Thus, patients with NAFLD, depending on BMI, have a different combination of risk factors, the model of which includes both important features of nutritional status and metabolic and hormonal disorders that underlie the formation of the disease as a whole. The resulting combinations of factors can be used for early diagnosis of NAFLD in patients with both obesity and normal body weight as an expanded screening.

non-alcoholic fatty liver disease, nutritional status, visfatin, bioimpedansometry, assessment of actual nutrition, gamma-glutamyl transpeptidase, HOMA-IR index

1. Lazebnik L.B., Turkina S.V. NAFLD - associated comorbidity. Experimental Clinical Gastroenterology. 2021;(10): 5-13. (In Russ.) doi: 10.31146/1682-8658-есд-194-10-5-13.@@ Лазебник Л.Б., Туркина С.В. НАЖБП - ассоциированная коморбидность. Экспериментальная и клиническая гастроэнтерология. 2021; 10: 5-13. doi: 10.31146/1682-8658-есд-194-10-5-13.

2. Krolevets T.S., Livzan M.A. Non-alcoholic fatty liver disease: digest 2021. Evidence-based Gastroenterology. 2021;(10): 27-35. (In Russ.) doi: 10.17116/dokgastro20211002127.@@ Кролевец Т.С., Ливзан М.А. Неалкогольная жировая болезнь печени: дайджест 2021. Доказательная гастроэнтерология. 2021;(10):27-35. doi: 10.17116/dokgastro20211002127.

3. Xian Y.X., Weng J.P., Xu F. MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy. Chin Med J. 2020; 134:8-19 doi: 10.1097/CM9.0000000000001263.

4. Younossi ZM, Stepanova M, Younossi Y, Golabi P. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut. 2020;69(3):564-568. doi: 10.1136/gutjnl-2019-318813.

5. Lazebnik L.B., Golovanova E.V., Turkina S.V. et al. Non-alcoholic fatty liver disease in adults: clinical picture, diagnosis, treatment. Recommendations 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 др. 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.

6. Tsygankova O.V., Badin A.R., Starichkov A.A., Lozhkina N.G. Non-alcoholic fatty liver disease: a disease of civilization or a syndrome of modern age? RMJ. Medical Review. 2018; 3: 23-28. (in Russ.) doi: 10.17116/dokgastro20221101120.@@ Цыганкова О.В., Бадин А.Р., Старичков А.А., Ложкина Н.Г. Неалкогольная жировая болезнь печени - болезнь цивилизации или синдром современности? РМЖ;2018; 3:23-28. doi: 10.17116/dokgastro20221101120.

7. Maurizio Parola, Massimo Pinzani, Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies, Molecular Aspects of Medicine, 2024; 95: 191-213. doi: 10.1016/j.mam.2023.101231.

8. Bekaert M., Verhelst X., Geerts A. Association of recently described adipokines with liver histology in biopsy-proven non-alcoholic fatty liver disease: A systematic review Obes. Rev. 2016;(17): 68-80. doi: 10.1111/obr.12333.

9. Eng J.M., Estall J.L. Diet-Induced Models of Non-Alcoholic Fatty Liver Disease: Food for Thought on Sugar, Fat, and Cholesterol. Cells, 2021;(10):1805-1903. doi: 10.3390/cells10071805.

10. Ren X.Y., Shi D., Ding J. et al. Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: jinchang cohort study. Lipids Health Dis. 2019;18:47. doi: 10.1186/s12944-019-0984-9.

11. Zeng P., Cai X., Yu X., Huang L., Chen X. HOMA-IR is an effective biomarker of non-alcoholic fatty liver disease in non-diabetic population. Journal of International Medical Research. 2023;51(10): 1231-1242. doi: 10.1177/03000605231204462.

12. Methodological recommendations MR 2.3.1.0253-21 “Norms for physiological needs for energy and nutrients for various groups of the population of the Russian Federation” (approved by the Federal Service for Surveillance on Consumer Rights Protection and Human Welfare on July 22, 2021) Introduced to replace MR 2.3.1.2432-08. (in Russ.)@@ Методические рекомендации MP 2.3.1.0253-21 «Нормы физиологических потребностей в энергии и пищевых веществах для различных групп населения Российской Федерации» (утв. Федеральной службой по надзору в сфере защиты прав потребителей и благополучия человека 22 июля 2021 г.) Введены взамен MP 2.3.1.2432-08.

13. Yadgarov M. Ya., Berikashvili L.B., Kadantseva K.K. Multivariate analysis in clinical medicine.Russian Journal of Anesthesiology and Reanimatology. 2021;(5):64-70. (in Russ.) doi: 10.17116/anaesthesiology202105164.@@ Ядгаров М.Я., Берикашвили Л.Б., Каданцева К.К. Многофакторный анализ в клинической медицине. Анестезиология и реаниматология. 2021;(5):64-70. doi: 10.17116/anaesthesiology202105164.

14. Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, Qiu Y, Burns L, Afendy A, Nader F. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol. 2019;71(4):793-801. doi: 10.1016/j.jhep.2019.06.021.

15. Hu S., Wang L., Yang D. et al. Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice. Cell Metab. 2018 Sep 4;28(3):415-431.e4. doi: 10.1016/j.cmet.2018.06.010.

16. González-Blázquez R., Alcalá M., Fernández-Alfonso M.S. et al. Relevance of control diet choice in metabolic studies: impact in glucose homeostasis and vascular function. Sci Rep. 2020 Feb 19;10(1):2902. doi: 10.1038/s41598-020-59674-0.

17. Taniguchi, H., Ueda, M., Sano, F., Kobayashi, Y. Dietary characteristics associated with the risk of non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease in non-obese Japanese participants: A cross-sectional study. JGH Open, 2024; 8: e13082. doi: 10.1002/jgh3.13082.

18. Cohen D.E., Fisher E.A. Lipoprotein metabolism, dyslipidemia, and nonalcoholic fatty liver disease. Semin Liver Dis. 2013;33:380-388. doi: 10.1055/s-0033-1358519.

19. Tang Z., Pham M., Hao Y. et al. Sex, Age, and BMI modulate the association of physical examinations and blood biochemistry parameters and NAFLD: a retrospective study on 1994 cases observed at Shuguang hospital, China. Biomed Res Int. 2019; 20(19):1246-1253. doi: 10.1155/2019/1246518.

20. Li Q., Zhang X., Zhang C. et al. Risk factors and prediction models for nonalcoholic fatty liver disease based on random forest.Comput Math Methods Med. 2022; 8(7): 936-959. doi: 10.1155/2022/8793659.

21. Ren X.Y., Shi D., Ding J. et al. Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: jinchang cohort study. Lipids Health Dis. 2019;18:47-62. doi: 10.1186/s12944-019-0984-9.

22. Qiu J., Huang X., Kuang M., Yang R., Li J., Sheng G., Zou Y. Lipoprotein Combine Index as a Better Marker for NAFLD Identification Than Traditional Lipid Parameters. Diabetes Metab Syndr Obes. 2024;17:2583-2595 doi: 10.2147/DMSO.S462181.

23. Albhaisi S., Chowdhury A., Sanyal A.J. Non-alcoholic fatty liver disease in lean individuals. JHEP Rep. 2019 Aug 30;1(4):329-341. doi: 10.1016/j.jhepr.2019.08.002.

24. Machado M.V. Nonalcoholic fatty liver disease in lean subjects: Is it all metabolic-associated fatty liver disease? Hepatoma Res. 2020; 6; 84-99.

25. Seaw K.M., Henry C.J., Bi, X. Relationship between Non-Alcoholic Fatty Liver Disease and Visceral Fat Measured by Imaging-Based Body Composition Analysis: A Systematic Review. Livers 2023; 3: 463-493. doi: 10.3390/livers3030033.

26. Ismaiel A., Leucuta D.C., Popa S.L. Serum visfatin levels in nonalcoholic fatty liver disease and liver fibrosis: Systematic review and meta-analysis. J. Clin. Med. 2021; 10:3029-3042. doi: 10.3390/jcm10143029.

27. Younossi Z.M., Noureddin M., Bernstein D. Role of noninvasive tests in clinical gastroenterology practices to identify patients with nonalcoholic steatohepatitis at high risk of adverse outcomes: expert panel recommendations. Am.J. Gastroenterol., 2021; 116: 254-262 doi: 10.14309/ajg.0000000000001054.

28. Hernandez Roman J. et al.The role of noninvasive biomarkers in diagnosis and risk stratification in nonalcoholic fatty liver disease. EndocrinolDiabetes Metab. 2020; 3: 432-456.

29. Feng G., Feng L., Zhao Y. Association between ratio of γ-glutamyl transpeptidase to high-density lipoprotein cholesterol and prevalence of nonalcoholic fatty liver disease and metabolic syndrome: a cross-sectional study. Ann Transl Med. 2020;8(10):634-643. doi: 10.21037/atm-19-4516.

30. Diagnostic performance of the GGT/HDL-C ratio for NAFLD in adults with obesity undergoing bariatric surgery. Diabetes Research and Clinical Practice. 2024; 211: 111649. doi: 10.1016/j.diabres.2024.111649.