Metabolic dysfunctionassociated steatotic liver disease in the setting of metabolic syndrome
https://doi.org/10.31146/1682-8658-ecg-235-3-55-65
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology, affecting about 38% of the global population. It represents a spectrum of conditions, starting from the fat accumulation in hepatocytes (steatosis) and progressing to liver inflammation (steatohepatitis) with varying degrees of fibrosis, as well as a risk of developing cirrhosis and hepatocellular carcinoma. With the accumulation of scientific data and improvements in diagnostic methods, an understanding has emerged that metabolic dysfunction is central to the pathogenesis and consequences of NAFLD. In 2020 a proposal was made to revise the nomenclature and classification of NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD), emphasizing the underlying metabolic dysfunction of this condition. This review discusses the differences in the definitions and classification of NAFLD and MASLD, the clinical burden and consequences of MASLD as a multisystem disease, with a focus on the pathogenetic interrelationships between MASLD and metabolic syndrome.
Keywords
About the Authors
O. V. Tsygankova
Novosibirsk State Medical University; Research Institute of Internal and Preventive Medicine - Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
V. V. Veretyuk
Novosibirsk State Medical University
Russian Federation
Russian Federation
O. V. Timoshchenko
Research Institute of Internal and Preventive Medicine - Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
References
1. Lim S., Kim J.W., Targher G. Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease. Trends Endocrinol Metab. 2021 Jul;32(7):500-514. doi: 10.1016/j.tem.2021.04.008.
2. Eslam M., Newsome P.N., Sarin S.K. et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020 Jul;73(1):202-209. doi: 10.1016/j.jhep.2020.03.039.
3. Li Y.Y., Zheng T.L., Xiao S.Y. et al. Hepatocytic ballooning in non-alcoholic steatohepatitis: Dilemmas and future directions. Liver Int. 2023 Jun;43(6):1170-1182. doi: 10.1111/liv.15571.
4. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024 Sep;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031.
5. Lemieux I., Després J.P. Metabolic Syndrome: Past, Present and Future. Nutrients. 2020 Nov 14;12(11):3501. doi: 10.3390/nu12113501.
6. Cornier M.A., Dabelea D., Hernandez T.L. et al. The metabolic syndrome. Endocr Rev. 2008 Dec;29(7):777-822. doi: 10.1210/er.2008-0024.
7. Alberti K.G., Eckel R.H., Grundy S.M. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5. doi: 10.1161/CIRCULATIONAHA.109.192644.
8. Mychka V.B., Zhernakova Yu.V., Chazova I.E. The recommendations of the experts of allRussian scientific society of cardiology for the diagnosis and treatment of metabolic syndrome (second revision). Doctor.Ru. 2010;(3):15-8. (in Russ.)@@ Мычка В.Б., Жернакова Ю.В., Чазова И.Е. Рекомендации экспертов Всероссийского научного общества кардиологов по диагностике и лечению метаболического синдрома (второй пересмотр). Доктор.ру. 2010;(3): 15-8.
9. Tang S.Y., Tan J.S., Pang X.Z., Lee G.H. Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact. World J Gastroenterol. 2023 Jan 21;29(3):549-560. doi: 10.3748/wjg.v29.i3.549.
10. Chan K.E., Koh T.J.L., Tang A.S.P. et al. Global Prevalence and Clinical Characteristics of Metabolic-associated Fatty Liver Disease: A Meta-Analysis and Systematic Review of 10 739 607 Individuals. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2691-2700. doi: 10.1210/clinem/dgac321.
11. 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.
12. Melnichenko G.A., Yeliseyeva A. Yu., Mayevskaya M.V. Prevalence of non-alcoholic fatty liver disease at obesity and its interrelation with cardio-vascular disease and 2nd type diabetes mellitus risk factors.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2012;22(2):45-53. (In Russ.)@@ Мельниченко Г.А., Елисеева А.Ю., Маевская М.В. Распространенность неалкогольной жировой болезни печени при ожирении и ее взаимосвязь с факторами риска сердечно-сосудистых заболеваний и сахарного диабета 2-го типа. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2012;22(2):45-53.
13. Ivashkin V.T., Drapkina O.M., Mayev I.V. et al. Prevalence of non-alcoholic fatty liver disease in out-patients of the Russian Federation: DIREG 2 study results.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(6):31-41. (In Russ.)@@ Ивашкин В.Т., Драпкина О.М., Маев И.В. и соавт. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлинической практики в Российской Федерации: результаты исследования DIREG 2. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2015;25(6):31-41.
14. Liu J., Ayada I., Zhang X. et al. Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults. Clin Gastroenterol Hepatol. 2022 Mar;20(3): e573-e582. doi: 10.1016/j.cgh.2021.02.030.
15. Fu C.E., Ng C.H., Yong J.N. et al. A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease. Endocr Pract. 2023 Jan;29(1):33-39. doi: 10.1016/j.eprac.2022.10.007.
16. Xiao J., Ng C.H., Chan K.E. et al. Hepatic, Extra-hepatic Outcomes and Causes of Mortality in NAFLD - An Umbrella Overview of Systematic Review of Meta-Analysis. J Clin Exp Hepatol. 2023 Jul-Aug;13(4):656-665. doi: 10.1016/j.jceh.2022.11.006.
17. Ford E.S. The metabolic syndrome and mortality from cardiovascular disease and all-causes: findings from the National Health and Nutrition Examination Survey II Mortality Study. Atherosclerosis. 2004 Apr;173(2):309-14. doi: 10.1016/j.atherosclerosis.2003.12.022.
18. Wu S.H., Liu Z., Ho S.C. Metabolic syndrome and all-cause mortality: a meta-analysis of prospective cohort studies. Eur J Epidemiol. 2010 Jun;25(6):375-84. doi: 10.1007/s10654-010-9459-z.
19. Gathirua-Mwangi W.G., Monahan P.O., Murage M.J., Zhang J. Metabolic syndrome and total cancer mortality in the Third National Health and Nutrition Examination Survey. Cancer Causes Control. 2017 Feb;28(2):127-136. doi: 10.1007/s10552-016-0843-1.
20. Bruno G., Merletti F., Biggeri A. et al. Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study. Diabetes Care. 2004 Nov;27(11):2689-94. doi: 10.2337/diacare.27.11.2689.
21. Fu C.E., Yong J.N., Ng C.H. et al. The prognostic value of including non-alcoholic fatty liver disease in the definition of metabolic syndrome. Aliment Pharmacol Ther. 2023 May;57(9):979-987. doi: 10.1111/apt.17397.
22. Nguyen V.H., Le M.H., Cheung R.C., Nguyen M.H. Differential Clinical Characteristics and Mortality Outcomes in Persons With NAFLD and/or MAFLD. Clin Gastroenterol Hepatol. 2021 Oct;19(10):2172-2181.e6. doi: 10.1016/j.cgh.2021.05.029.
23. Moretti V., Romeo S., Valenti L. The contribution of genetics and epigenetics to MAFLD susceptibility. Hepatol Int. 2024 Apr 25. doi: 10.1007/s12072-024-10667-5.
24. Chitturi S., Abeygunasekera S., Farrell G.C. et al. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002 Feb;35(2):373-9. doi: 10.1053/jhep.2002.30692.
25. Samuel V.T., Shulman G.I. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016 Jan;126(1):12-22. doi: 10.1172/JCI77812.
26. Kuchay M.S., Choudhary N.S., Mishra S.K. Pathophysiological mechanisms underlying MAFLD. Diabetes Metab Syndr. 2020 Nov-Dec;14(6):1875-1887. doi: 10.1016/j.dsx.2020.09.026.
27. Ametov A.S., Tsygankova O.V.Complex metabolic protection as a modern strategy for the management of type 2 diabetes mellitus. Endocrinology: News, Opinions, Training. 2021; 10(2):93-104. (In Russ.) doi: 10.33029/2304-9529-2021-10-2-93-104.@@ Аметов А.С., Цыганкова О.В. Комплексная метаболическая протекция как современная стратегия управления сахарным диабетом 2 типа. Эндокринология: новости, мнения, обучение. 2021; 10(2):93-104. doi: 10.33029/2304-9529-2021-10-2-93-104.
28. Tsygankova O.V., Veretyuk V.V., Mareev V.Yu. Modification of the of the cardiometabolic profile using combined therapy of the angiotensin receptor-neprilysin inhibitor and empagliflozin in comorbid patients with Chronic Heart Failure and type 2 Diabetes Mellitus. Kardiologiia. 2020;60(5):146-152. (In Russ.) doi: 10.18087/cardio.2020.5.n840.@@ Цыганкова О.В., Веретюк В.В., Мареев В.Ю. Возможности положительной модификации кардиометаболического профиля при совместном назначении ангиотензиновых рецепторов-неприлизина ингибитора и эмпаглифлозина у коморбидных пациентов с хронической сердечной недостаточностью и сахарным диабетом 2 типа. Кардиология. 2020;60(5):146-152. doi: 10.18087/cardio.2020.5.n840.
29. Mouzaki M., Comelli E.M., Arendt B.M. et al.Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013 Jul;58(1):120-7. doi: 10.1002/hep.26319.
30. Wong V.W., Tse C.H., Lam T.T. et al. Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis - a longitudinal study. PLoS One. 2013 Apr 25;8(4): e62885. doi: 10.1371/journal.pone.0062885.
31. Ferrara C.M., Goldberg A.P., Ortmeyer H.K., Ryan A.S. Effects of aerobic and resistive exercise training on glucose disposal and skeletal muscle metabolism in older men. J Gerontol A Biol Sci Med Sci. 2006 May;61(5):480-7. doi: 10.1093/gerona/61.5.480.
32. Stangl M.K., Böcker W., Chubanov V. et al. Sarcopenia - Endocrinological and Neurological Aspects. Exp Clin Endocrinol Diabetes. 2019 Jan;127(1):8-22. doi: 10.1055/a-0672-1007.
33. Wijarnpreecha K., Kim D., Raymond P., Scribani M., Ahmed A. Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA. Eur J Gastroenterol Hepatol. 2019 Sep;31(9):1121-1128. doi: 10.1097/MEG.0000000000001397.
34. Pedersen B.K., Febbraio M.A. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012 Apr 3;8(8):457-65. doi: 10.1038/nrendo.2012.49.
35. Collino M., Mastrocola R., Nigro D. et al. Variability in myosteatosis and insulin resistance induced by high-fat diet in mouse skeletal muscles. Biomed Res Int. 2014;2014:569623. doi: 10.1155/2014/569623.
36. Zhang H.J., Zhang X.F., Ma Z.M. et al. Irisin is inversely associated with intrahepatic triglyceride contents in obese adults. J Hepatol. 2013 Sep;59(3):557-62. doi: 10.1016/j.jhep.2013.04.030.
37. Wang X., Hu Z., Hu J., Du J., Mitch W.E. Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology. 2006 Sep;147(9):4160-8. doi: 10.1210/en.2006-0251.
38. Koo B.K., Kim D., Joo S.K. et al. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J Hepatol. 2017 Jan;66(1):123-131. doi: 10.1016/j.jhep.2016.08.019.
39. Targher G., Valenti L., Byrne C.D. Metabolic Dysfunction-Associated Steatotic Liver Disease. N Engl J Med. 2025 Aug 14;393(7):683-698. doi: 10.1056/NEJMra2412865.
40. Radu F., Potcovaru C.G., Salmen T. et al. The Link between NAFLD and Metabolic Syndrome. Diagnostics (Basel). 2023 Feb 7;13(4):614. doi: 10.3390/diagnostics13040614.
41. Cotter T.G., Rinella M. Nonalcoholic Fatty Liver Disease 2020: The State of the Disease. Gastroenterology. 2020 May;158(7):1851-1864. doi: 10.1053/j.gastro.2020.01.052.
42. Marchesini G., Bugianesi E., Forlani G. et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003 Apr;37(4):917-23. doi: 10.1053/jhep.2003.50161.
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Tsygankova O.V., Veretyuk V.V., Timoshchenko O.V. Metabolic dysfunctionassociated steatotic liver disease in the setting of metabolic syndrome. Experimental and Clinical Gastroenterology. 2025;(3):55-65. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-235-3-55-65
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