Clinical Guidelines of the Russian Society for the Study of the Liver, Russian Gastroenterological Association, Russian Society for the Prevention of Non-Communicable Diseases, Russian Association of Endocrinologists, Russian Scientific Medical Society of Therapists, National Society of Preventive Cardiology, Russian Association of Gerontologists and Geriatricians on Non-Alcoholic Fatty Liver Disease

Aim. The clinical guidelines are intended to provide information support for making decisions by gastroenterologists, general practitioners and internists that will improve the quality of medical care for patients with non-alcoholic fatty liver disease, taking into account the latest clinical data and principles of evidence-based medicine.
Key points. Clinical guidelines contain information about current views on etiology, risk factors and pathogenesis of nonalcoholic fatty liver disease, peculiarities of its clinical course. Also given recommendations provide information on current methods of laboratory and instrumental diagnostics, invasive and non-invasive tools for nonalcoholic fatty liver disease and its clinical phenotypes assessment, approaches to its treatment, considering the presence of comorbidities, features of dispensary monitoring and prophylaxis. The information is illustrated with algorithms of differential diagnosis and physician's actions. In addition, there is information for the patient and criteria for assessing the quality of medical care.
Conclusion. Awareness of specialists in the issues of diagnosis, treatment and follow-up of patients with nonalcoholic fatty liver disease contributes to the timely diagnosis and initiation of treatment, which in the long term will significantly affect their prognosis and quality of life.

1. Rinella M.E., Neuschwander-Tetri B.A., Siddiqui M.S., Abdelmalek M.F., Caldwell S., Barb D., et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797–835. DOI: 10.1097/HEP.0000000000000323

2. Rinella M.E., Lazarus J.V., Ratziu V., Francque S.M., Sanyal A.J., Kanwal F., et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966–86. DOI: 10.1097/HEP.0000000000000520

3. ICD-11. International Classification of Diseases 11th Revision. URL: https://icd.who.int

4. Singh S., Allen A.M., Wang Z., Prokop L.J., Murad M.H., Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: A systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643–54.e1–9. DOI: 10.1016/j.cgh.2014.04.014

5. Raikhelson K.L., Maevskaya M.V., Zharkova M.S., Grechishnikova V.R., Okovityi S.V., Deeva T.A., et al. Steatotic liver disease: New nomenclature and its localization in the Russian Federation. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2024;34(2):35–44. (In Russ.). DOI: 10.22416/1382-4376-2024-961

6. Day C.P., James O.F. Steatohepatitis: A tale of two “hits”? Gastroenterology. 1998;114(4):842–5. DOI: 10.1016/s0016-5085(98)70599-2

7. Byrne C.D., Targher G. NAFLD: A multisystem disease. J Hepatol. 2015;62(Suppl. 1):S47–64. DOI: 10.1016/j.jhep.2014.12.012

8. 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 (Engl). 2020;134(1):8–19. DOI: 10.1097/CM9.0000000000001263

9. Parthasarathy G., Revelo X., Malhi H. Pathogenesis of nonalcoholic steatohepatitis: An overview. Hepatol Commun. 2020;4(4):478–92. DOI: 10.1002/hep4.1479

10. Haas J.T., Francque S., Staels B. Pathophysiology and mechanisms of nonalcoholic fatty liver disease. Annu Rev Physiol. 2016;78:181–205. DOI: 10.1146/annurev-physiol-021115-105331

11. Basaranoglu M., Basaranoglu G., Bugianesi E. Carbohydrate intake and nonalcoholic fatty liver disease: Fructose as a weapon of mass destruction. Hepatobiliary Surg Nutr. 2015;4(2):109–16. DOI: 10.3978/j.issn.2304-3881.2014.11.05

12. Jensen T., Abdelmalek M.F., Sullivan S., Nadeau K.J., Green M., Roncal C., et al. Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. J Hepatol. 2018;68(5):1063–75. DOI: 10.1016/j.jhep.2018.01.019

13. Birkenfeld A.L., Shulman G.I. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology. 2014;59(2):713–23. DOI: 10.1002/hep.26672

14. Ipsen D.H., Lykkesfeldt J., Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci. 2018;75(18):3313–27. DOI: 10.1007/s00018-018-2860-6

15. Lambert J.E., Ramos-Roman M.A., Browning J.D., Parks E.J. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014;146(3):726–35. DOI: 10.1053/j.gastro.2013.11.049

16. Ter Horst K.W., Serlie M.J. Fructose consumption, lipogenesis, and non-alcoholic fatty liver disease. Nutrients. 2017;9(9):981. DOI: 10.3390/nu9090981

17. Shen J., Sakaida I., Uchida K., Terai S., Okita K. Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells. Life Sci. 2005;77(13):1502–15. DOI: 10.1016/j.lfs.2005.04.004

18. Subichin M., Clanton J., Makuszewski M., Bohon A., Zografakis J.G., Dan A. Liver disease in the morbidly obese: A review of 1000 consecutive patients undergoing weight loss surgery. Surg Obes Relat Dis. 2015;11(1):137–41. DOI: 10.1016/j.soard.2014.06.015

19. Sasaki A., Nitta H., Otsuka K., Umemura A., Baba S., Obuchi T., et al. Bariatric surgery and non-alcoholic fatty liver disease: Current and potential future treatments. Front Endocrinol (Lausanne). 2014;5:164. DOI: 10.3389/fendo.2014.00164

20. Stojsavljević S., Gomerčić Palčić M., Virović Jukić L., Smirčić Duvnjak L., Duvnjak M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(48):18070–91. DOI: 10.3748/wjg.v20.i48.18070

21. Osborn O., Olefsky J.M. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18(3):363–74. DOI: 10.1038/nm.2627

22. Yan F.J., Wang X., Wang S.E., Hong H.T., Lu J., Ye Q., et al. C-Jun/C7ORF41/NF-κB axis mediates hepatic inflammation and lipid accumulation in NAFLD. Biochem J. 2020;477(3):691–708. DOI: 10.1042/BCJ20190799

23. Jin S., Li Y., Xia T., Liu Y., Zhang S., Hu H., et al. Mechanisms and therapeutic implications of selective autophagy in nonalcoholic fatty liver disease. J Adv Res. 2025:67:317–29. DOI: 10.1016/j.jare.2024.01.027

24. Prerna K., Dubey V.K. Beclin1-mediated interplay between autophagy and apoptosis: New understanding. Int J Biol Macromol. 2022;204:258–73. DOI: 10.1016/j.ijbiomac.2022.02.005

25. Fromenty B., Roden M. Mitochondrial alterations in fatty liver diseases. J Hepatol. 2023;78(2):415–29. DOI: 10.1016/j.jhep.2022.09.020

26. Ferré P., Foufelle F. SREBP-1c transcription factor and lipid homeostasis: Clinical perspective. Horm Res. 2007;68(2):72–82. DOI: 10.1159/000100426

27. Miserez A.R., Muller P.Y., Barella L., Barella S., Staehelin H.B., Leitersdorf E., et al. Sterol-regulatory element-binding protein (SREBP)-2 contributes to polygenic hypercholesterolaemia. Atherosclerosis. 2002;164(1):15–26. DOI: 10.1016/s0021-9150(01)00762-6

28. Iizuka K., Takao K., Yabe D. ChREBP-mediated regulation of lipid metabolism: Involvement of the gut microbiota, liver, and adipose tissue. Front Endocrinol (Lausanne). 2020;11:587189. DOI: 10.3389/fendo.2020.587189

29. Ma M., Xie W., Li X. Identification of autophagy-related genes in the progression from non-alcoholic fatty liver to non-alcoholic steatohepatitis. Int J Gen Med. 2021;14:3163–76. DOI: 10.2147/IJGM.S317785

30. Barrientos-Riosalido A., Real M., Bertran L., Aguilar C., Martínez S., Parada D., et al. Increased hepatic ATG7 mRNA and ATG7 protein expression in nonalcoholic steatohepatitis associated with obesity. Int J Mol Sci. 2023;24(2):1324. DOI: 10.3390/ijms24021324

31. Syed-Abdul M.M. Lipid metabolism in metabolic-associated steatotic liver disease (MASLD). Metabolites. 2023;14(1):12. DOI: 10.3390/metabo14010012

32. Branković M., Dukić M., Gmizić T., Popadić V., Nikolić N., Sekulić A., et al. New therapeutic approaches for the treatment of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and increased cardiovascular risk. Diagnostics (Basel). 2024;14(2):229. DOI: 10.3390/diagnostics14020229

33. Zhao Y., Zhou Y., Wang D., Huang Z., Xiao X., Zheng Q., et al. Mitochondrial dysfunction in metabolic dysfunction fatty liver disease (MAFLD). Int J Mol Sci. 2023;24(24):17514. DOI: 10.3390/ijms242417514

34. Chen Z., Tian R., She Z., Cai J., Li H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med. 2020;152:116–41. DOI: 10.1016/j.freeradbiomed.2020.02.025

35. Thomson A.W., Knolle P.A. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol. 2010;10(11):753–66. DOI: 10.1038/nri2858

36. Lotze M.T., Zeh H.J., Rubartelli A., Sparvero L.J., Amoscato A.A., Washburn N.R., et al. The grateful dead: Damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol Rev. 2007;220:60–81. DOI: 10.1111/j.1600-065X.2007.00579.x

37. Szabo G., Csak T. Inflammasomes in liver diseases. J Hepatol. 2012;57(3):642–54. DOI: 10.1016/j.jhep.2012.03.035

38. Luedde T., Schwabe R.F. NF-κB in the liver — linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2011;8(2):108–18. DOI: 10.1038/nrgastro.2010.213

39. Klein I., Cornejo J.C., Polakos N.K., John B., Wuensch S.A., Topham D.J., et al. Kupffer cell heterogeneity: Functional properties of bone marrow derived and sessile hepatic macrophages. Blood. 2007;110(12):4077–85. DOI: 10.1182/blood-2007-02-073841

40. Fang Y.L., Chen H., Wang C.L., Liang L. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”. World J Gastroenterol. 2018;24(27):2974–83. DOI: 10.3748/wjg.v24.i27.2974

41. Tomita K., Tamiya G., Ando S., Ohsumi K., Chiyo T., Mizutani A., et al. Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice. Gut. 2006;55(3):415–24. DOI: 10.1136/gut.2005.071118

42. Kremer M., Hines I.N., Milton R.J., Wheeler M.D. Favored T helper 1 response in a mouse model of hepatosteatosis is associated with enhanced T cell-mediated hepatitis. Hepatology. 2006;44(1):216–27. DOI: 10.1002/hep.21221

43. Ghazarian M., Revelo X.S., Nøhr M.K., Luck H., Zeng K., Lei H., et al. Type I interferon Responses drive intrahepatic T cells to promote metabolic syndrome. Sci Immunol. 2017;2(10):eaai7616. DOI: 10.1126/sciimmunol.aai7616

44. Wang M., Li L., Xu Y., Du J., Ling C. Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis. Front Pharmacol. 2022;13:958428. DOI: 10.3389/fphar.2022.958428

45. Li Z., Yuan H., Chu H., Yang L. The crosstalk between gut microbiota and bile acids promotes the development of non-alcoholic fatty liver disease. Microorganisms. 2023;11(8):2059. DOI: 10.3390/microorganisms11082059

46. Clemente M.G., Mandato C., Poeta M., Vajro P. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World J Gastroenterol. 2016;22(36):8078–93. DOI: 10.3748/wjg.v22.i36.8078

47. Ulluwishewa D., Anderson R.C., McNabb W.C., Moughan P.J., Wells J.M., Roy N.C. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr. 2011;141(5):769–76. DOI: 10.3945/jn.110.135657

48. Paolella G., Mandato C., Pierri L., Poeta M., Di Stasi M., Vajro P. Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20(42):15518–31. DOI: 10.3748/wjg.v20.i42.15518

49. Zorn A.M., Wells J.M. Vertebrate endoderm development and organ formation. Annu Rev Cell Dev Biol. 2009;25:221–51. DOI: 10.1146/annurev.cellbio.042308.113344

50. Fairfield C.J., Drake T.M., Pius R., Bretherick A.D., Campbell A., Clark D.W., et al. Genome-wide association study of NAFLD using electronic health records. Hepatol Commun. 2022;6(2):297–308. DOI: 10.1002/hep4.1805

51. Anstee Q.M., Darlay R., Cockell S., Meroni M., Govaere O., Tiniakos D., et al. Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort. J Hepatol. 2020;73(3):505–15. DOI: 10.1016/j.jhep.2020.04.003

52. Kurtanov K.A., Sydykova L.A., Pavlova N.I., Filippova N.P., Dodokhov V.V., Apsolikhova G.A., et al. Polymorphism of the adiponutrin gene (PNPLA3) in the indigenous inhabitants of the Republic of Sakha (Yakutia) with type 2 diabetes mellitus. Almanac of Clinical Medicine. 2018;46(3):258–63 (In Russ.). DOI: 10.18786/2072-0505-2018-46-3-258-263

53. Krolevets T.S., Livzan M.A., Akhmedov V.A., Novikov D.G. Study of PNPLA3 gene polymorphism in patients with non-alcoholic fatty liver disease and various stages of fibrosis. Experimental and Clinical Gastroenterology. 2018;11:24–32. (In Russ.).

54. Raikhelson K.L., Kovyazina V.P., Sidorenko D.V., Nazarov V.D., Lapin S.V., Emanuel V.L., et al. PNPLA3 gene polymorphism impact on the nonalcoholic fatty liver disease course. RMJ. 2019;12:85–8. (In Russ.).

55. Dyakonova A.T., Kurtanov K.A., Pavlova N.I., Soloveva N.A., Soloveva Yu.A., Filippova N.P., et al. Polymorphism rs58542926 of the TM6SF2 gene in chronic non-infectious liver diseases in the Yakut population. Modern Problems of Science and Education. 2019;6:133. (In Russ.). DOI: 10.17513/spno.29334

56. Cusi K., Isaacs S., Barb D., Basu R., Caprio S., Garvey W.T., et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: Co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022;28(5):528–62. DOI: 10.1016/j.eprac.2022.03.010

57. Lonardo A., Ballestri S., Mantovani A., Nascimbeni F., Lugari S., Targher G. Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity? Dig Liver Dis. 2019;51(4):462–70. DOI: 10.1016/j.dld.2018.12.014

58. Ramanathan R., Patwa S.A., Ali A.H., Ibdah J.A. Thyroid hormone and mitochondrial dysfunction: Therapeutic implications for metabolic dysfunction-associated steatotic liver disease (MASLD). Cells. 2023;12(24):2806. DOI: 10.3390/cells12242806

59. Younossi Z.M., Henry L. Understanding the burden of nonalcoholic fatty liver disease: Time for action. Diabetes Spectr. 2024;37(1):9–19. DOI: 10.2337/dsi23-0010

60. Jichitu A., Bungau S., Stanescu A.M.A., Vesa C.M., Toma M.M., Bustea C., et al. Non-alcoholic fatty liver disease and cardiovascular comorbidities: Pathophysiological links, diagnosis, and therapeutic management. Diagnostics (Basel). 2021;11(4):689. DOI: 10.3390/diagnostics11040689

61. Drapkina O.M., Ivashkin V.T. Epidemiological features of non-alcoholic fatty liver disease in Russia (results of an open multi-center prospective observational study DIREG L 01903). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2014;24(4):32–8. (In Russ.).

62. Ivashkin V.T., Drapkina O.M., Mayev I.V., Trukhmanov A.S., Blinov D.V., Palgova L.K., 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.).

63. Evstifeeva S.E., Shalnova S.A., Kutsenko V.A., Yarovaya E.V., Balanova Yu.A., Imaeva A.E., 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

64. 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):313–19. (In Russ.). DOI: 10.26442/20751753.2023.5.202155

65. Povsic M., Wong O.Y., Perry R., Bottomley J. A structured literature review of the epidemiology and disease burden of non-alcoholic steatohepatitis (NASH). Adv Ther. 2019;36(7):1574–94. DOI: 10.1007/s12325-019-00960-3

66. Harrison S.A., Gawrieh S., Roberts K., Lisanti C.J., Schwope R.B., Cebe K.M., et al. Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort. J Hepatol. 2021;75(2):284–91. DOI: 10.1016/j.jhep.2021.02.034

67. Estes C., Anstee Q.M., Arias-Loste M.T., Bantel H., Bellentani S., Caballeria J., 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;69(4):896–904. DOI: 10.1016/j.jhep.2018.05.036

68. Huang D.Q., Terrault N.A., Tacke F., Gluud L.L., Arrese M., Bugianesi E., et al. Global epidemiology of cirrhosis — aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol. 2023;20(6):388–98. DOI: 10.1038/s41575-023-00759-2

69. Huang D.Q., El-Serag H.B., Loomba R. Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18(4):223–38. DOI: 10.1038/s41575-020-00381-6

70. Ivashkin V.T., Maevskaya M.V., Zharkova M.S., Zhigalova S.B., Kitsenko E.A., Manukyan G.V., et al. Liver cirrhosis and fibrosis: Clinical guidelines. Moscow; 2021. (In Russ.).

71. Muthiah M.D., Cheng Han N., Sanyal A.J. A clinical overview of non-alcoholic fatty liver disease: A guide to diagnosis, the clinical features, and complications — What the non-specialist needs to know. Diabetes Obes Metab. 2022;24(Suppl. 2):3–14. DOI: 10.1111/dom.14521

72. Cook N., Geier A., Schmid A., Hirschfield G., Kautz A., Schattenberg J.M., et al. The patient perspectives on future therapeutic options in NASH and patient needs. Front Med (Lausanne). 2019;6:61. DOI: 10.3389/fmed.2019.00061

73. Liebe R., Esposito I., Bock H.H., Vom Dahl S., Stindt J., Baumann U., et al. Diagnosis and management of secondary causes of steatohepatitis. J Hepatol. 2021;74(6):1455–71. DOI: 10.1016/j.jhep.2021.01.045

74. Ivashkin V.T. Propaedeutics of internal diseases: textbook. 2nd ed. Moscow: GEOTAR-Media Publ.; 2023. (In Russ.).

75. Ivashkin V.T., Maevskaya M.V., Zharkova M.S., Kotovskaya Yu.V., Tkacheva O.N., Troshina E.A., 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):104–40. (In Russ). DOI: 10.22416/1382-4376-2022-32-4-104-140

76. Obika M., Noguchi H. Diagnosis and evaluation of nonalcoholic fatty liver disease. Exp Diabetes Res. 2012;2012:145754. DOI: 10.1155/2012/145754

77. Pavlov Ch.S., Glushenkov D.V., Konovalova O.N., Ivashkin V.T. The scope of clinical application of noninvasive methods for assessing liver fibrosis: Results of our own studies in a multidisciplinary hospital. Clinical Medicine. 2009;87(11):40–5. (In Russ.).

78. Sorbi D., Boynton J., Lindor K.D. The ratio of aspartate aminotransferase to alanine aminotransferase: Potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol. 1999;94(4):1018–22. DOI: 10.1111/j.1572-0241.1999.01006.x

79. Dedov I.I., Shestakova M.V., Mayorov A.Yu., Shamkhalova M.Sh., Sukhareva O.Yu., Galstyan G.R., et al. Type 2 diabetes mellitus in adults: Clinical guidelines. Moscow; 2022. (In Russ.).

80. Fujii H., Kawada N.; Japan Study Group Of Nafld Jsg-Nafld. The role of insulin resistance and diabetes in nonalcoholic fatty liver disease. Int J Mol Sci. 2020;21(11):3863. DOI: 10.3390/ijms21113863

81. Targher G., Day C.P., Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363(14):1341–50. DOI: 10.1056/NEJMra0912063

82. Kutishenko N.P., Martsevich S.Yu., Lerman O.V., Balashov I.S., Nevzorova V.A., Reznik I.I., et al. The improvement of lipid-lowering therapy effectiveness in patients with high cardiovascular risk and concomitant liver disease (results of additional analysis of the RAKURS study). Rational Pharmacotherapy in Cardiology. 2015;11(3):297–303. (In Russ.). DOI: 10.20996/1819-6446-2015-11-3-297-303

83. Ezhov M.V., Kukharchuk V.V., Sergienko I.V., Alieva A.S., Antsiferov M.B., Ansheles A.A., et al. Lipid metabolism disorders: Clinical guidelines. Moscow; 2023. (In Russ.).

84. Spinosa M., Stine J.G. Nonalcoholic fatty liver disease — evidence for a thrombophilic state? Curr Pharm Des. 2020;26(10):1036–44. DOI: 10.2174/1381612826666200131101553

85. Verrijken A., Francque S., Mertens I., Prawitt J., Caron S., Hubens G., et al. Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2014;59(1):121–9. DOI: 10.1002/hep.26510

86. Balta G., Altay C., Gurgey A. PAI-1 gene 4G/5G genotype: A risk factor for thrombosis in vessels of internal organs. Am J Hematol. 2002;71(2):89–93. DOI: 10.1002/ajh.10192

87. Northup P.G., Argo C.K., Shah N., Caldwell S.H. Hypercoagulation and thrombophilia in nonalcoholic fatty liver disease: Mechanisms, human evidence, therapeutic implications, and preventive implications. Semin Liver Dis. 2012;32(1):39–48. DOI: 10.1055/s-0032-1306425

88. Skurk T., Hauner H. Obesity and impaired fibrinolysis: Role of adipose production of plasminogen activator inhibitor-1. Int J Obes Relat Metab Disord. 2004;28(11):1357–64. DOI: 10.1038/sj.ijo.0802778

89. Kotronen A., Joutsi-Korhonen L., Sevastianova K., Bergholm R., Hakkarainen A., Pietiläinen K.H., et al. Increased coagulation factor VIII, IX, XI and XII activities in non-alcoholic fatty liver disease. Liver Int. 2011;31(2):176–83. DOI: 10.1111/j.1478-3231.2010.02375.x

90. Ciardullo S., Ballabeni C., Trevisan R., Perseghin G. Liver stiffness, albuminuria and chronic kidney disease in patients with NAFLD: A systematic review and meta-analysis. Biomolecules. 2022;12(1):105. DOI: 10.3390/biom12010105

91. Sun D.Q., Jin Y., Wang T.Y., Zheng K.I., Rios R.S., Zhang H.Y., et al. MAFLD and risk of CKD. Metabolism. 2021;115:154433. DOI: 10.1016/j.metabol.2020.154433

92. Bobkova I.N., Vatazin A.V., Vetchinnikova O.N., Volgina G.V., Golubev R.V., Gorelova E.A., et al. Chronic kidney disease (CKD): Clinical guidelines. Moscow; 2021. (In Russ.).

93. Maevskaya M.V., Kotovskaya Yu.V., Ivashkin V.T., Tkacheva O.N., Troshina E.A., Shestakova M.V., et al. The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities. Terapevticheskii Arkhiv. 2022;94(2):216–53. (In Russ.). DOI: 10.26442/00403660.2022.02.201363

94. Darmawan G., Hamijoyo L., Hasan I. Association between serum uric acid and non-alcoholic fatty liver disease: A meta-analysis. Acta Med Indones. 2017;49(2):136–47.

95. Lombardi R., Pisano G., Fargion S. Role of serum uric acid and ferritin in the development and progression of NAFLD. Int J Mol Sci. 2016;17(4):548. DOI: 10.3390/ijms17040548

96. Averkina N.A., Bagaeva M.E., Batysheva T.T., Bykova O.V., Vashakmadze N.D., Volynets G.V., et al. Copper metabolism disorders (Wilson’s disease): Clinical guidelines. Moscow; 2021. (In Russ.).

97. Ivashkin V.T., Yushchuk N.D., Bogomolov P.O., Volchkova E.V., Dmitriev A.S., Zharkova M.S., et al. Chronic viral hepatitis C: Clinical recommendations. Moscow; 2021. (In Russ.).

98. Ivashkin V.T., Maevskaya M.V., Zharkova M.S., Tikhonov I.N., Fedosina E.A., Pavlov Ch.S. Algorithms for diagnosis and treatment in hepatology: Reference materials. Moscow: MEDpress-inform Publ.; 2016. (In Russ.).

99. Petzold G. Role of ultrasound methods for the assessment of NAFLD. J Clin Med. 2022;11(15):4581. DOI: 10.3390/jcm11154581

100. Ferraioli G., Soares Monteiro L.B. Ultrasound-based techniques for the diagnosis of liver steatosis. World J Gastroenterol. 2019;25(40):6053–62. DOI: 10.3748/wjg.v25.i40.6053

101. Hernaez R., Lazo M., Bonekamp S., Kamel I., Brancati F.L., Guallar E., et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: A meta-analysis. Hepatology. 2011;54(3):1082–90. DOI: 10.1002/hep.24452

102. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis — 2021 update. J Hepatol. 2021;75(3):659–89. DOI: 10.1016/j.jhep.2021.05.025

103. Petroff D., Blank V., Newsome P.N., Shalimar, Voican C.S., Thiele M., et al. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: An individual patient data meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(3):185–98. DOI: 10.1016/S2468-1253(20)30357-5

104. Pu K., Wang Y., Bai S., Wei H., Zhou Y., Fan J., et al. Diagnostic accuracy of controlled attenuation parameter (CAP) as a non-invasive test for steatosis in suspected non-alcoholic fatty liver disease: A systematic review and meta-analysis. BMC Gastroenterol. 2019;19(1):51. DOI: 10.1186/s12876-019-0961-9

105. Gu J., Liu S., Du S., Zhang Q., Xiao J., Dong Q., et al. Diagnostic value of MRI-PDFF for hepatic steatosis in patients with non-alcoholic fatty liver disease: A meta-analysis. Eur Radiol. 2019;29(7):3564–73. DOI: 10.1007/s00330-019-06072-4

106. Verhaegh P., Bavalia R., Winkens B., Masclee A., Jonkers D., Koek G. Noninvasive tests do not accurately differentiate nonalcoholic steatohepatitis from simple steatosis: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018;16(6):837–61. DOI: 10.1016/j.cgh.2017.08.024

107. Kleiner D.E., Brunt E.M. Nonalcoholic fatty liver disease: Pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis. 2012;32(1):3–13. DOI: 10.1055/s-0032-1306421

108. Kleiner D.E., Brunt E.M., Van Natta M., Behling C., Contos M.J., Cummings O.W., et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21. DOI: 10.1002/hep.20701

109. Bedossa P. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology. 2014;60(2):565–75. DOI: 10.1002/hep.27173

110. Bedossa P. Current histological classification of NAFLD: Strength and limitations. Hepatol Int. 2013;7(Suppl. 2):765–70. DOI: 10.1007/s12072-013-9446-z

111. Harrison S.A., Torgerson S., Hayashi P., Ward J., Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003;98(11):2485–90. DOI: 10.1111/j.1572-0241.2003.08699.x

112. Xiao G., Zhu S., Xiao X., Yan L., Yang J., Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology. 2017;66(5):1486–501. DOI: 10.1002/hep.29302

113. McPherson S., Hardy T., Dufour J.F., Petta S., Romero-Gomez M., Allison M., et al. Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am J Gastroenterol. 2017;112(5):740–51. DOI: 10.1038/ajg.2016.453

114. Bril F., McPhaul M.J., Caulfield M.P., Clark V.C., Soldevilla-Pico C., Firpi-Morell R.J., et al. Performance of plasma biomarkers and diagnostic panels for nonalcoholic steatohepatitis and advanced fibrosis in patients with type 2 diabetes. Diabetes Care. 2020;43(2):290–7. DOI: 10.2337/dc19-1071

115. Ratziu V., Massard J., Charlotte F., Messous D., Imbert-Bismut F., Bonyhay L., et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2006;6:6. DOI: 10.1186/1471-230X-6-6

116. Vali Y., Lee J., Boursier J., Spijker R., Verheij J., Brosnan M.J., et al. FibroTest for evaluating fibrosis in non-alcoholic fatty liver disease patients: A systematic review and meta-analysis. J Clin Med. 2021;10(11):2415. DOI: 10.3390/jcm10112415

117. Papatheodoridi M., Hiriart J.B., Lupsor-Platon M., Bronte F., Boursier J., Elshaarawy O., et al. Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease. J Hepatol. 2021;74(5):1109–16. DOI: 10.1016/j.jhep.2020.11.050

118. De Franchis R., Bosch J., Garcia-Tsao G., Reiberger T., Ripoll C. Baveno VII — Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–74. DOI: 10.1016/j.jhep.2021.12.022

119. World Health Organization. WHO guidelines on physical activity and sedentary behaviour. URL: https://iris.who.int/bitstream/handle/10665/336656/9789240015128-eng.pdf

120. Keating S.E., Hackett D.A., George J., Johnson N.A. Exercise and non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Hepatol. 2012;57(1):157–66. DOI: 10.1016/j.jhep.2012.02.023

121. Dedov I.I., Mokrysheva N.G., Melnichenko G.A., Troshina E.A., Mazurina N.V., Ershova E.V., et al. Obesity: Clinical guidelines. Moscow; 2020. (In Russ.).

122. Hashida R., Kawaguchi T., Bekki M., Omoto M., Matsuse H., Nago T., et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review. J Hepatol. 2017;66(1):142–52. DOI: 10.1016/j.jhep.2016.08.023

123. Katsagoni C.N., Georgoulis M., Papatheodoridis G.V., Panagiotakos D.B., Kontogianni M.D. Effects of lifestyle interventions on clinical characteristics of patients with non-alcoholic fatty liver disease: A meta-analysis. Metabolism. 2017;68:119–32. DOI: 10.1016/j.metabol.2016.12.006

124. Golabi P., Locklear C.T., Austin P., Afdhal S., Byrns M., Gerber L., et al. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review. World J Gastroenterol. 2016;22(27):6318–27. DOI: 10.3748/wjg.v22.i27.6318

125. Smart N.A., King N., McFarlane J.R., Graham P.L., Dieberg G. Effect of exercise training on liver function in adults who are overweight or exhibit fatty liver disease: A systematic review and meta-analysis. Br J Sports Med. 2018;52(13):834–43. DOI: 10.1136/bjsports-2016-096197

126. Cheng S., Ge J., Zhao C., Le S., Yang Y., Ke D., et al. Effect of aerobic exercise and diet on liver fat in pre-diabetic patients with non-alcoholic-fatty-liver-disease: A randomized controlled trial. Sci Rep. 2017;7(1):15952. DOI: 10.1038/s41598-017-16159-x

127. Hallsworth K., Thoma C., Hollingsworth K.G., Cassidy S., Anstee Q.M., Day C.P., et al. Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: A randomized controlled trial. Clin Sci (Lond). 2015;129(12):1097–105. DOI: 10.1042/CS20150308

128. Rector R.S., Thyfault J.P., Morris R.T., Laye M.J., Borengasser S.J., Booth F.W., et al. Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats. Am J Physiol Gastrointest Liver Physiol. 2008;294(3):G619–26. DOI: 10.1152/ajpgi.00428.2007

129. Rinella M.E., Neuschwander-Tetri B.A., Siddiqui M.S., Abdelmalek M.F., Caldwell S., Barb D., et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797–835. DOI: 10.1097/HEP.0000000000000323

130. Zelber-Sagi S., Salomone F., Mlynarsky L. The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: Evidence and plausible mechanisms. Liver Int. 2017;37(7):936–49. DOI: 10.1111/liv.13435

131. Haigh L., Kirk C., El Gendy K., Gallacher J., Errington L., Mathers J.C., et al. The effectiveness and acceptability of Mediterranean diet and calorie restriction in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis. Clin Nutr. 2022;41(9):1913–31. DOI: 10.1016/j.clnu.2022.06.037

132. Younossi Z.M., Corey K.E., Lim J.K. AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: Expert review. Gastroenterology. 2021;160(3):912–8. DOI: 10.1053/j.gastro.2020.11.051

133. Panchal S.K., Poudyal H., Brown L. Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. J Nutr. 2012;142(6):1026–32. DOI: 10.3945/jn.111.157263

134. Aller R., Izaola O., de la Fuente B., De Luis Román D.A. Mediterranean diet is associated with liver histology in patients with non alcoholic fatty liver disease. Nutr Hosp. 2015;32(6):2518–24. DOI: 10.3305/nh.2015.32.6.10074

135. Abenavoli L., Greco M., Nazionale I., Peta V., Milic N., Accattato F., et al. Effects of Mediterranean diet supplemented with silybin-vitamin E-phospholipid complex in overweight patients with non-alcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol. 2015;9(4):519–27. DOI: 10.1586/17474124.2015.1004312

136. Ryan M.C., Itsiopoulos C., Thodis T., Ward G., Trost N., Hofferberth S., et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013;59(1):138–43. DOI: 10.1016/j.jhep.2013.02.012

137. Trovato F.M., Martines G.F., Brischetto D., Trovato G., Catalano D. Neglected features of lifestyle: Their relevance in non-alcoholic fatty liver disease. World J Hepatol. 2016;8(33):1459–65. DOI: 10.4254/wjh.v8.i33.1459

138. Lee D., Chiavaroli L., Ayoub-Charette S., Khan T.A., Zurbau A., Au-Yeung F., et al. Important food sources of fructose-containing sugars and non-alcoholic fatty liver disease: A systematic review and meta-analysis of controlled trials. Nutrients. 2022;14(14):2846. DOI: 10.3390/nu14142846

139. Liu W., Zhai D., Zhang T., Mudoti N.G., Chang Q., Liu Y., et al. Meta-analysis of the association between major foods with added fructose and non-alcoholic fatty liver disease. Food Funct. 2023;14(12):5551–61. DOI: 10.1039/d3fo00882g

140. Zhang X.L., Wang T.Y., Targher G., Byrne C.D., Zheng M.H. Lifestyle interventions for non-obese patients both with, and at risk, of non-alcoholic fatty liver disease. Diabetes Metab J. 2022;46(3):391–401. DOI: 10.4093/dmj.2022.0048

141. Wong V.W., Wong G.L., Chan R.S., Shu S.S., Cheung B.H., Li L.S., et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol. 2018;69(6):1349–56. DOI: 10.1016/j.jhep.2018.08.011

142. Long M.T., Noureddin M., Lim J.K. AGA clinical practice update: Diagnosis and management of nonalcoholic fatty liver disease in lean individuals: Expert review. Gastroenterology. 2022;163(3):764–74.e1. DOI: 10.1053/j.gastro.2022.06.023

143. Francque S.M., Marchesini G., Kautz A., Walmsley M., Dorner R., Lazarus J.V., et al. Non-alcoholic fatty liver disease: A patient guideline. JHEP Rep. 2021;3(5):100322. DOI: 10.1016/j.jhepr.2021.100322

144. Jarvis H., O’Keefe H., Craig D., Stow D., Hanratty B., Anstee Q.M. Does moderate alcohol consumption accelerate the progression of liver disease in NAFLD? A systematic review and narrative synthesis. BMJ Open. 2022;12(1):e049767. DOI: 10.1136/bmjopen-2021-049767

145. Di Ciaula A., Bonfrate L., Krawczyk M., Frühbeck G., Portincasa P. Synergistic and detrimental effects of alcohol intake on progression of liver steatosis. Int J Mol Sci. 2022;23(5):2636. DOI: 10.3390/ijms23052636

146. Long M.T., Massaro J.M., Hoffmann U., Benjamin E.J., Naimi T.S. Alcohol use is associated with hepatic steatosis among persons with presumed nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2020;18(8):1831–41.e5. DOI: 10.1016/j.cgh.2019.11.022

147. El Hadi H., Di Vincenzo A., Vettor R., Rossato M. Cardio-metabolic disorders in non-alcoholic fatty liver disease. Int J Mol Sci. 2019;20(9):2215. DOI: 10.3390/ijms20092215

148. Lizardi-Cervera J., Aguilar-Zapata D. Nonalcoholic fatty liver disease and its association with cardiovascular disease. Ann Hepatol. 2009;8(Suppl. 1):S40–3. DOI: 10.1016/S1665-2681(19)31825-3

149. Angulo P., Kleiner D.E., Dam-Larsen S., Adams L.A., Bjornsson E.S., Charatcharoenwitthaya P., et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389–97.e10. DOI: 10.1053/j.gastro.2015.04.043

150. Kwo P.Y., Cohen S.M., Lim J.K. ACG clinical guideline: Evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18–35. DOI: 10.1038/ajg.2016.517

151. Kim H.C., Nam C.M., Jee S.H., Han K.H., Oh D.K., Suh I. Normal serum aminotransferase concentration and risk of mortality from liver diseases: Prospective cohort study. BMJ. 2004;328(7446):983. DOI: 10.1136/bmj.38050.593634.63

152. Lee T.H., Kim W.R., Benson J.T., Therneau T.M., Melton L.J. 3rd. Serum aminotransferase activity and mortality risk in a United States community. Hepatology. 2008;47(3):880–7. DOI: 10.1002/hep.22090

153. Ruhl C.E., Everhart J.E. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology. 2009;136(2):477–85.e11. DOI: 10.1053/j.gastro.2008.10.052

154. Ioannou G.N., Weiss N.S., Boyko E.J., Mozaffarian D., Lee S.P. Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Hepatology. 2006;43(5):1145–51. DOI: 10.1002/hep.21171

155. Buzzetti E., Linden A., Best L.M., Madden A.M., Roberts D., Chase T.J.G., et al. Lifestyle modifications for nonalcohol-related fatty liver disease: A network meta-analysis. Cochrane Database Syst Rev. 2021;6(6):CD013156. DOI: 10.1002/14651858.CD013156.pub2

156. Komolafe O., Buzzetti E., Linden A., Best L.M., Madden A.M., Roberts D., et al. Nutritional supplementation for nonalcohol-related fatty liver disease: A network meta-analysis. Cochrane Database Syst Rev. 2021;7(7):CD013157. DOI: 10.1002/14651858.CD013157.pub2

157. Romero-Gómez M., Zelber-Sagi S., Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67(4):829–46. DOI: 10.1016/j.jhep.2017.05.016

158. Peng L., Wang J., Li F. Weight reduction for non-alcoholic fatty liver disease. Cochrane Database Syst Rev. 2011;6:CD003619. DOI: 10.1002/14651858.CD003619.pub3

159. Xiang Z., Chen Y.P., Ma K.F., Ye Y.F., Zheng L., Yang Y.D., et al. The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: A systematic review. BMC Gastroenterol. 2013;13:140. DOI: 10.1186/1471-230X-13-140

160. Simental-Mendía M., Sánchez-García A., Simental-Mendía L.E. Effect of ursodeoxycholic acid on liver markers: A systematic review and meta-analysis of randomized placebo-controlled clinical trials. Br J Clin Pharmacol. 2020;86(8):1476–88. DOI: 10.1111/bcp.14311

161. Laurin J., Lindor K.D., Crippin J.S., Gossard A., Gores G.J., Ludwig J., et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: A pilot study. Hepatology. 1996;23(6):1464–7. DOI: 10.1002/hep.510230624

162. Ozel Coskun B.D., Yucesoy M., Gursoy S., Baskol M., Yurci A., Yagbasan A., et al. Effects of ursodeoxycholic acid therapy on carotid intima media thickness, apolipoprotein A1, apolipoprotein B, and apolipoprotein B/A1 ratio in nonalcoholic steatohepatitis. Eur J Gastroenterol Hepatol. 2015;27(2):142–9. DOI: 10.1097/MEG.0000000000000264

163. Ratziu V., de Ledinghen V., Oberti F., Mathurin P., Wartelle-Bladou C., Renou C., et al. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011;54(5):1011–9. DOI: 10.1016/j.jhep.2010.08.030

164. Pavlov Ch.S., Varganova D.L., Semenistaya M.Ch., Kuznetsova E.A., Usanova A.A., Svistunov A.A. Ursodeoxycholic acid: Efficacy and safety in the treatment of nonalcoholic fatty liver disease (meta-analysis). Annals of the Russian Academy of Medical Sciences. 2018;73(5):294–305. (In Russ.). DOI: 10.15690/vramn975

165. Zhang W., Tang Y., Huang J., Hu H. Efficacy of ursodeoxycholic acid in nonalcoholic fatty liver disease: An updated meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2020;29(4):696–705. DOI: 10.6133/apjcn.202012_29(4).0004

166. Lin X., Mai M., He T., Huang H., Zhang P., Xia E., et al. Efficiency of ursodeoxycholic acid for the treatment of nonalcoholic steatohepatitis: A systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2022;16(6):537–45. DOI: 10.1080/17474124.2022.2083605

167. Nadinskaia M., Maevskaya M., Ivashkin V., Kodzoeva K., Pirogova I., Chesnokov E., et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(10):959–75. DOI: 10.3748/wjg.v27.i10.959

168. Byrnes K., Blessinger S., Bailey N.T., Scaife R., Liu G., Khambu B. Therapeutic regulation of autophagy in hepatic metabolism. Acta Pharm Sin B. 2022;12(1):33–49. DOI: 10.1016/j.apsb.2021.07.021

169. Decuypere J.P., Parys J.B., Bultynck G. Regulation of the autophagic bcl-2/beclin 1 interaction. Cells. 2012;1(3):284–312. DOI: 10.3390/cells1030284

170. Carino A., Biagioli M., Marchianò S., Fiorucci C., Zampella A., Monti M.C., et al. Ursodeoxycholic acid is a GPBAR1 agonist and resets liver/intestinal FXR signaling in a model of diet-induced dysbiosis and NASH. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(10):1422–37. DOI: 10.1016/j.bbalip.2019.07.006

171. Marchianò S., Biagioli M., Roselli R., Zampella A., Di Giorgio C., Bordoni M., et al. Beneficial effects of UDCA and norUDCA in a rodent model of steatosis are linked to modulation of GPBAR1/FXR signaling. Biochim Biophys Acta Mol Cell Biol Lipids. 2022;1867(11):159218. DOI: 10.1016/j.bbalip.2022.159218

172. Karedath J., Javed H., Ahsan Talpur F., Lal B., Kumari A., Kivan H., et al. Effect of vitamin E on clinical outcomes in patients with non-alcoholic fatty liver disease: A meta-analysis. Cureus. 2022;14(12):e32764. DOI: 10.7759/cureus.32764

173. Bril F., Biernacki D.M., Kalavalapalli S., Lomonaco R., Subbarayan S.K., Lai J., et al. Role of vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: A randomized controlled trial. Diabetes Care. 2019;42(8):1481–8. DOI: 10.2337/dc19-0167

174. Xu R., Tao A., Zhang S., Deng Y., Chen G. Association between vitamin E and non-alcoholic steatohepatitis: A meta-analysis. Int J Clin Exp Med. 2015;8(3):3924–34.

175. Mazhar I.J., Yasir M., Sarfraz S., Shlaghya G., Narayana S.H., Mushtaq U., et al. Vitamin E and pioglitazone: A comprehensive systematic review of their efficacy in non-alcoholic fatty liver disease. Cureus. 2023;15(8):e43635. DOI: 10.7759/cureus.43635

176. Vilar-Gomez E., Vuppalanchi R., Gawrieh S., Ghabril M., Saxena R., Cummings O.W., et al. Vitamin E improves transplant-free survival and hepatic decompensation among patients with nonalcoholic steatohepatitis and advanced fibrosis. Hepatology. 2020;71(2):495–509. DOI: 10.1002/hep.30368

177. 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 for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–402. DOI: 10.1016/j.jhep.2015.11.004

178. Chalasani N., Younossi Z., Lavine J.E., Charlton M., Cusi K., Rinella M., 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;67(1):328–57. DOI: 10.1002/hep.29367

179. Sanyal A.J., Chalasani N., Kowdley K.V., McCullough A., Diehl A.M., Bass N.M., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675–85. DOI: 10.1056/NEJMoa0907929

180. Ando Y., Jou J.H. Nonalcoholic fatty liver disease and recent guideline updates. Clin Liver Dis (Hoboken). 2021;17(1):23–8. DOI: 10.1002/cld.1045

181. Bjelakovic G., Nikolova D., Gluud C. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: Do we have evidence for lack of harm? PLoS One. 2013;8(9):e74558. DOI: 10.1371/journal.pone.0074558

182. Miller E.R. 3rd, Pastor-Barriuso R., Dalal D., Riemersma R.A., Appel L.J., Guallar E. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37–46. DOI: 10.7326/0003-4819-142-1-200501040-00110

183. Curtis A.J., Bullen M., Piccenna L., McNeil J.J. Vitamin E supplementation and mortality in healthy people: A meta-analysis of randomised controlled trials. Cardiovasc Drugs Ther. 2014;28(6):563–73. DOI: 10.1007/s10557-014-6560-7

184. Vivarelli F., Canistro D., Cirillo S., Papi A., Spisni E., Vornoli A., et al. Co-carcinogenic effects of vitamin E in prostate. Sci Rep. 2019;9(1):11636. DOI: 10.1038/s41598-019-48213-1

185. Podszun M., Frank J. Vitamin E-drug interactions: Molecular basis and clinical relevance. Nutr Res Rev. 2014;27(2):215–31. DOI: 10.1017/S0954422414000146

186. Noureddin M., Sander-Struckmeier S., Mato J.M. Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review. World J Hepatol. 2020;12(2):46–63. DOI: 10.4254/wjh.v12.i2.46

187. Raikhelson K.L., Kondrashina E.A. Ademethionine in the treatment of fatigue in liver diseases: A systematic review. Terapevticheskii Arkhiv. 2019;91(2):134–42. (In Russ.). DOI: 10.26442/00403660.2019.02.000130

188. Baranovsky A.Yu., Raykhelson K.L., Marchenko N.V. Application of S-adenosylmethionine (Heptral®) in treatment of patients with non-alcoholic steatohepatitis. Clinical Perspectives of Gastroenterology, Hepatology. 2010;9(1):3–10. (In Russ.).

189. Shankar R., Virukalpattigopalratnam M.P., Singh T. Heptral® (Ademetionine) in intrahepatic cholestasis due to chronic non-alcoholic liver disease: Subgroup analysis of results of a multicentre observational study in India. J Clin Exp Hepatol. 2014;4(Suppl. 2):S33. DOI: 10.1016/j.jceh.2014.02.071

190. Li H., Liu N.N., Peng Z.G. Effect of bicyclol on blood biomarkers of NAFLD: A systematic review and meta-analysis. BMJ Open. 2020;10(12):e039700. DOI: 10.1136/bmjopen-2020-039700

191. Maevskaya M.V., Lunkov V.D., Geyvandova N.I., Palgova L.K., Pirogova I.Yu., Prashnova M.K., et al. Bicyclol in the treatment of patients with chronic diffuse liver diseases. Medical Council. 2020;(15):78–89. (In Russ.). DOI: 10.21518/2079-701X-2020-15-78-89

192. Pan S.Y., Dong H., Yu Z.L., Zhao X.Y., Xiang C.J., Wang H., et al. Bicyclol, a synthetic dibenzocyclooctadiene derivative, decreases hepatic lipids but increases serum triglyceride level in normal and hypercholesterolaemic mice. J Pharm Pharmacol. 2007;59(12):1657–62. DOI: 10.1211/jpp.59.12.0007

193. Pan S.Y., Yu Z.L., Dong H., Xiang C.J., Fong W.F., Ko K.M. Ethanol extract of fructus schisandrae decreases hepatic triglyceride level in mice fed with a high fat/cholesterol diet, with attention to acute toxicity. Evid Based Complement Alternat Med. 2011;2011:729412. DOI: 10.1093/ecam/nep070

194. Zhao W., Yan Y., Xiao Z., Wang M., Xu M., Wang Z., et al. Bicyclol ameliorates nonalcoholic fatty liver disease in mice via inhibiting MAPKs and NF-κB signaling pathways. Biomed Pharmacother. 2021;141:111874. DOI: 10.1016/j.biopha.2021.111874

195. Pirogova I.Yu., Yakovleva S.V., Neuymina T.V., Sinitsyn S.P., Chulkov V.S., Shamaeva T.N. Efficacy and safety of bicyclol treatment for non-alcoholic fatty liver disease: Results of a cohort study. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(4):66–75. (In Russ.). DOI: 10.22416/1382-4376-2018-28-4-66-75

196. Okovity S.V., Prikhodko V.A., Bezborodkina N.N., Kudryavtsev B.N. Hepatoprotectors: A guide for doctors. 2nd ed. Moscow: GEOTAR-Media Publ.; 2022. (In Russ.). DOI: 10.33029/9704-6689-6-LIV-1-240

197. Semiserin V.A., Karakozov A.G., Malkuta M.A., Zolotareva L.A., Levchenko O.B., Kalyagin I.E., et al. Evaluation of the efficiency of hepatoprotective monotherapy using succinic acid and methionine for nonalcoholic fatty liver disease at the stage of steatohepatitis. Terapevticheskii Arkhiv. 2016;88(2):58–63. (In Russ.). DOI: 10.17116/terarkh201688258-63

198. Stelmakh V.V., Kozlov V.K., Baranov V.L., Latariya E.L., Nekrasova A.S. Energy-tropic pathogenetically oriented therapy with succinate-containing drugs in non-alcoholic fatty liver disease: Prospects for clinical use. Medical Alphabet. 2013;1(2):38–44. (In Russ.).

199. Dudorenko S.V., Kovalenko A.L., Prokopenko S.M., Belogurova E.V. The use of remaxol in the treatment of metabolic syndrome in patients with nonalcoholic steatohepatitis and diabetes mellitus 2 type. Experimental and Clinical Gastroenterology. 2016;6:89–94. (In Russ.).

200. Shipovskaya A.A., Dudanova O.P. Intrahepatic cholestasis in nonalcoholic fatty liver disease. Terapevticheskii Arkhiv. 2018;90(2):69–74. (In Russ.). DOI: 10.26442/terarkh201890269-74

201. Pennisi G., Pipitone R.M., Grimaudo S., Spatola F., Di Martino V., Cammà C., et al. A cholestatic pattern predicts liver outcomes in patients with nonalcoholic fatty liver disease. Dig Liver Dis. 2021;53(Suppl. 1):S27. DOI: 10.1016/j.dld.2020.12.069

202. Shirokova Ye.N. Intrahepatic cholestasis in non-alcoholic fatty liver disease: Pathogenesis and role of ademetionine in treatment. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2023;33(2):79–86. (In Russ.). DOI: 10.22416/1382-4376-2023-33-2-79-86

203. Anstee Q.M., Day C.P. S-adenosylmethionine (SAMe) therapy in liver disease: A review of current evidence and clinical utility. J Hepatol. 2012;57(5):1097–109. DOI: 10.1016/j.jhep.2012.04.041

204. Butterworth R.F., Kircheis G., Hilger N., McPhail M.J.W. Efficacy of l-ornithine l-aspartate for the treatment of hepatic encephalopathy and hyperammonemia in cirrhosis: Systematic review and meta-analysis of randomized controlled trials. J Clin Exp Hepatol. 2018;8(3):301–13. DOI: 10.1016/j.jceh.2018.05.004

205. Ermolova T.V., Ermolov S.Yu., Sologub T.V., Karev V.E., Dobkes A.L., Apresyan A.G. Portohepatic hemodynamic disturbances in patients with chronic liver disease at the initial stages of fibrosis and their correction. Farmateka. 2016;(15):58–66. (In Russ.).

206. Zykina E.J., Simonova Zh.G. Hyperammonemia in patients with stable angina pectoris and nonalcoholic fatty liver disease at the steatosis stage. Experimental and Clinical Gastroenterology. 2023;8:57–65. (In Russ.). DOI: 10.31146/1682-8658-ecg-216-8-57-65

207. Garanina Е.V. Effect of L-ornithine-L-aspartate on liver fibrosis and steatosis in patients with metabolic-associated fatty liver disease (non-alcoholic fatty liver disease) and hyperammonaemia. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(4):31–6. (In Russ.). DOI: 10.22416/1382-4376-2021-31-4-31-36

208. Kaiser S., Gerok W., Häussinger D. Ammonia and glutamine metabolism in human liver slices: New aspects on the pathogenesis of hyperammonaemia in chronic liver disease. Eur J Clin Invest. 1988;18(5):535–42. DOI: 10.1111/j.1365-2362.1988.tb01053.x

209. De Chiara F., Heebøll S., Marrone G., Montoliu C., Hamilton-Dutoit S., Ferrandez A., et al. Urea cycle dysregulation in non-alcoholic fatty liver disease. J Hepatol. 2018;69(4):905–15. DOI: 10.1016/j.jhep.2018.06.023

210. Alekseenko S.A., Ageeva E.A., Polkovnikova О.P. Modern approaches to diagnostics and treatment of hyperammonemia in patients with chronic liver disease at a precirrhotic stage. RMJ. Medical Review. 2018;2(7-1):19–23. (In Russ.).

211. Tian L.Y., Lu L.G., Tang C.W., Xie Y., Luo H.S., Tan S.Y., et al. Aspartate-ornithine granules in the treatment of nonalcoholic steatohepatitis: A multiple-dose parallel controlled clinical trial. Zhonghua Gan Zang Bing Za Zhi. 2013;21(7):528–32. (In Chinese). DOI: 10.3760/cma.j.issn.1007-3418.2013.07.013

212. Pichon C., Nachit M., Gillard J., Vande Velde G., Lanthier N., Leclercq I.A. Impact of L-ornithine L-aspartate on non-alcoholic steatohepatitis-associated hyperammonemia and muscle alterations. Front Nutr. 2022;9:1051157. DOI: 10.3389/fnut.2022.1051157

213. Prikhodko V.A., Sysoev Yu.I., Poveryaeva M.A., Bunyat A.V., Karev V.E., Ivkin D.Yu., et al. Effects of empagliflozin and L-ornithine L-aspartate on behavior, cognitive functions, and physical performance in mice with experimentally induced steatohepatitis. Bulletin of Russian State Medical University. 2020;3:49–57. (In Russ.). DOI: 10.24075/brsmu.2020.034

214. Okovityi S.V.,Raikhelson K.L., Prikhodko V.A. Combined hepatoprotective pharmacotherapy for liver disease. Experimental and Clinical Gastroenterology. 2022;7:5–20. (In Russ.). DOI: 10.31146/1682-8658-ecg-203-7-5-20

215. Dufour J.F., Oneta C.M., Gonvers J.J., Bihl F., Cerny A., Cereda J.M., et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin E in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4(12):1537–43. DOI: 10.1016/j.cgh.2006.09.025

216. Pietu F., Guillaud O., Walter T., Vallin M., Hervieu V., Scoazec J.Y., et al. Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: Long-term results. Clin Res Hepatol Gastroenterol. 2012;36(2):146–55. DOI: 10.1016/j.clinre.2011.10.011

217. Balmer M.L., Siegrist K., Zimmermann A., Dufour J.F. Effects of ursodeoxycholic acid in combination with vitamin E on adipokines and apoptosis in patients with nonalcoholic steatohepatitis. Liver Int. 2009;29(8):1184–8. DOI: 10.1111/j.1478-3231.2009.02037.x

218. Thomsen M.N., Skytte M.J., Samkani A., Carl M.H., Weber P., Astrup A., et al. Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: A randomised controlled trial. Diabetologia. 2022;65(3):506–17. DOI: 10.1007/s00125-021-05628-8

219. Vilar-Gomez E., Martinez-Perez Y., Calzadilla-Bertot L., Torres-Gonzalez A., Gra-Oramas B., Gonzalez-Fabian L., et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367–78.e5. DOI: 10.1053/j.gastro.2015.04.005

220. Wong C., Lee M.H., Yaow C.Y.L., Chin Y.H., Goh X.L., Ng C.H., et al. Glucagon-like peptide-1 receptor agonists for non-alcoholic fatty liver disease in type 2 diabetes: A meta-analysis. Front Endocrinol (Lausanne). 2021;12:609110. DOI: 10.3389/fendo.2021.609110

221. Fan S., Shi X., Yao J., Zhong M., Feng P. The efficacy of glucagon-like peptide 1 receptor agonists in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Rev Esp Enferm Dig. 2020;112(8):627–35. DOI: 10.17235/reed.2020.6392/2019

222. Newsome P.N., Buchholtz K., Cusi K., Linder M., Okanoue T., Ratziu V., et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384(12):1113–24. DOI: 10.1056/NEJMoa2028395

223. Zhu K., Kakkar R., Chahal D., Yoshida E.M., Hussaini T. Efficacy and safety of semaglutide in non-alcoholic fatty liver disease. World J Gastroenterol. 2023;29(37):5327–38. DOI: 10.3748/wjg.v29.i37.5327

224. Bandyopadhyay S., Das S., Samajdar S.S., Joshi S.R. Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Diabetes Metab Syndr. 2023;17(10):102849. DOI: 10.1016/j.dsx.2023.102849

225. Gu Y., Sun L., Zhang W., Kong T., Zhou R., He Y., et al. Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials. Front Pharmacol. 2023;14:1102792. DOI: 10.3389/fphar.2023.1102792

226. Parab P., Chaudhary P., Mukhtar S., Moradi A., Kodali A., Okoye C., et al. Role of glucagon-like peptide-1 (GLP-1) receptor agonists in cardiovascular risk management in patients with type 2 diabetes mellitus: A systematic review. Cureus. 2023;15(9):e45487. DOI: 10.7759/cureus.45487

227. Banerjee M., Pal R., Mukhopadhyay S., Nair K. GLP-1 receptor agonists and risk of adverse cerebrovascular outcomes in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2023;108(7):1806–12. DOI: 10.1210/clinem/dgad076

228. Gomes D.A., Presume J., de Araújo Gonçalves P., Almeida M.S., Mendes M., Ferreira J. Association between the magnitude of glycemic control and body weight loss with GLP-1 receptor agonists and risk of atherosclerotic cardiovascular disease: A systematic review and meta-analyses of randomized diabetes cardiovascular outcomes trials. Cardiovasc Drugs Ther. 2024. DOI: 10.1007/s10557-024-07547-3

229. Cusi K., Orsak B., Bril F., Lomonaco R., Hecht J., Ortiz-Lopez C., et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: A randomized trial. Ann Intern Med. 2016;165(5):305–15. DOI: 10.7326/M15-1774

230. Musso G., Cassader M., Paschetta E., Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: A meta-analysis. JAMA Intern Med. 2017;177(5):633–40. DOI: 10.1001/jamainternmed.2016.9607

231. Zhao Y., Zhao W., Wang H., Zhao Y., Bu H., Takahashi H. Pioglitazone on nonalcoholic steatohepatitis: A systematic review and meta-analysis of 15 RCTs. Medicine (Baltimore). 2022;101(46):e31508. DOI: 10.1097/MD.0000000000031508

232. Ndakotsu A., Vivekanandan G. The role of thiazolidinediones in the amelioration of nonalcoholic fatty liver disease: A systematic review. Cureus. 2022;14(5):e25380. DOI: 10.7759/cureus.25380

233. Budd J., Cusi K. Role of agents for the treatment of diabetes in the management of nonalcoholic fatty liver disease. Curr Diab Rep. 2020;20(11):59. DOI: 10.1007/s11892-020-01349-1

234. State Register of Medicines. Pioglar. Number LS001671, registration date 16.07.2011. (In Russ.). URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=66ecaf50-2ba6-41a8-848f-de7e5b8c9220

235. Gautam A., Agrawal P.K., Doneria J., Nigam A. Effects of canagliflozin on abnormal liver function tests in patients of type 2 diabetes with non-alcoholic fatty liver disease. J Assoc Physicians India. 2018;66(8):62–6.

236. Wei Q., Xu X., Guo L., Li J., Li L. Effect of SGLT2 inhibitors on type 2 diabetes mellitus with non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2021;12:635556. DOI: 10.3389/fendo.2021.635556

237. Prikhodko V.A., Okovity S.V., Kulikov A.N. Gliflozins in non-alcoholic fatty liver disease: Perspectives of use outside diabetes, cardiac and nephroprotection. Therapy. 2023;9(7):130–41. (In Russ.). DOI: 10.18565/therapy.2023.7.130-141

238. Mo M., Huang Z., Liang Y., Liao Y., Xia N. The safety and efficacy evaluation of sodium-glucose co-transporter 2 inhibitors for patients with non-alcoholic fatty liver disease: An updated meta-analysis. Dig Liver Dis. 2022;54(4):461–8. DOI: 10.1016/j.dld.2021.08.017

239. Jin Z., Yuan Y., Zheng C., Liu S., Weng H. Effects of sodium-glucose co-transporter 2 inhibitors on liver fibrosis in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: An updated meta-analysis of randomized controlled trials. J Diabetes Complications. 2023;37(8):108558. DOI: 10.1016/j.jdiacomp.2023.108558

240. Ong Lopez A.M.C., Pajimna J.A.T. Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: An updated systematic review and meta-analysis. Sci Rep. 2024;14(1):2122. DOI: 10.1038/s41598-024-52603-5

241. Sánchez-García A., Sahebkar A., Simental-Mendía M., Simental-Mendía L.E. Effect of ursodeoxycholic acid on glycemic markers: A systematic review and meta-analysis of clinical trials. Pharmacol Res. 2018;135:144–9. DOI: 10.1016/j.phrs.2018.08.008

242. Elhini S.H., Wahsh E.A., Elberry A.A., El Ameen N.F., Abdelfadil Saedii A., Refaie S.M., et al. The impact of an SGLT2 inhibitor versus ursodeoxycholic acid on liver steatosis in diabetic patients. Pharmaceuticals (Basel). 2022;15(12):1516. DOI: 10.3390/ph15121516

243. Houttu V., Csader S., Nieuwdorp M., Holleboom A.G., Schwab U. Dietary interventions in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. Front Nutr. 2021;8:716783. DOI: 10.3389/fnut.2021.716783

244. Koutoukidis D.A., Astbury N.M., Tudor K.E., Morris E., Henry J.A., Noreik M., et al. Association of weight loss interventions with changes in biomarkers of nonalcoholic fatty liver disease: A systematic review and meta-analysis. JAMA Intern Med. 2019;179(9):1262–71. DOI: 10.1001/jamainternmed.2019.2248

245. Ezpeleta M., Gabel K., Cienfuegos S., Kalam F., Lin S., Pavlou V., et al. Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial. Cell Metab. 2023;35(1):56–70.e3. DOI: 10.1016/j.cmet.2022.12.001

246. Haufe S., Engeli S., Kast P., Böhnke J., Utz W., Haas V., et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology. 2011;53(5):1504–14. DOI: 10.1002/hep.24242

247. Asrih M., Jornayvaz F.R. Diets and nonalcoholic fatty liver disease: The good and the bad. Clin Nutr. 2014;33(2):186–90. DOI: 10.1016/j.clnu.2013.11.003

248. Lemstra M., Bird Y., Nwankwo C., Rogers M., Moraros J. Weight loss intervention adherence and factors promoting adherence: A meta-analysis. Patient Prefer Adherence. 2016;10:1547–59. DOI: 10.2147/PPA.S103649

249. Scragg J., Hallsworth K., Taylor G., Cassidy S., Haigh L., Boyle M., et al. Factors associated with engagement and adherence to a low-energy diet to promote 10 % weight loss in patients with clinically significant non-alcoholic fatty liver disease. BMJ Open Gastroenterol. 2021;8(1):e000678. DOI: 10.1136/bmjgast-2021-000678

250. Armstrong M.J., Gaunt P., Aithal G.P., Barton D., Hull D., Parker R., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679–90. DOI: 10.1016/S0140-6736(15)00803-X

251. Vilsbøll T., Christensen M., Junker A.E., Knop F.K., Gluud L.L. Effects of glucagon-like peptide-1 receptor agonists on weight loss: Systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771. DOI: 10.1136/bmj.d7771

252. Stokes C.S., Gluud L.L., Casper M., Lammert F. Ursodeoxycholic acid and diets higher in fat prevent gallbladder stones during weight loss: A meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2014;12(7):1090–100.e2. DOI: 10.1016/j.cgh.2013.11.031

253. Fearon N.M., Kearns E.C., Kennedy C.A., Conneely J.B., Heneghan H.M. The impact of ursodeoxycholic acid on gallstone disease after bariatric surgery: A meta-analysis of randomized control trials. Surg Obes Relat Dis. 2022;18(1):77–84. DOI: 10.1016/j.soard.2021.10.004

254. Mulliri A., Menahem B., Alves A., Dupont B. Ursodeoxycholic acid for the prevention of gallstones and subsequent cholecystectomy after bariatric surgery: A meta-analysis of randomized controlled trials. J Gastroenterol. 2022;57(8):529–39. DOI: 10.1007/s00535-022-01886-4

255. Machado F.H.F., Castro Filho H.F., Babadopulos R.F.A.L., Rocha H.A.L., Rocha J.L.C., Moraes Filho M.O. Ursodeoxycholic acid in the prevention of gallstones in patients subjected to Roux-en-Y gastric bypass1. Acta Cir Bras. 2019;34(1):e20190010000009. DOI: 10.1590/s0102-865020190010000009

256. Johansson K., Sundström J., Marcus C., Hemmingsson E., Neovius M. Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study. Int J Obes (Lond). 2014;38(2):279–84. DOI: 10.1038/ijo.2013.83

257. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol. 2016;65(1):146–81. DOI: 10.1016/j.jhep.2016.03.005

258. Uy M.C., Talingdan-Te M.C., Espinosa W.Z., Daez M.L., Ong J.P. Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: A meta-analysis. Obes Surg. 2008;18(12):1532–8. DOI: 10.1007/s11695-008-9587-7

259. Dongiovanni P., Petta S., Mannisto V., Mancina R.M., Pipitone R., Karja V., et al. Statin use and non-alcoholic steatohepatitis in at risk individuals. J Hepatol. 2015;63(3):705–12. DOI: 10.1016/j.jhep.2015.05.006

260. Zhou H., Toshiyoshi M., Zhao W., Zhao Y., Zhao Y. Statins on nonalcoholic fatty liver disease: A systematic review and meta-analysis of 14 RCTs. Medicine (Baltimore). 2023;102(26):e33981. DOI: 10.1097/MD.0000000000033981

261. Pastori D., Sciacqua A., Marcucci R., Del Ben M., Baratta F., Violi F., et al. Non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and cardiovascular events in atrial fibrillation. A prospective multicenter cohort study. Intern Emerg Med. 2021;16(8):2063–8. DOI: 10.1007/s11739-021-02682-3

262. Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–88. DOI: 10.1093/eurheartj/ehz455

263. Pastori D., Pani A., Di Rocco A., Menichelli D., Gazzaniga G., Farcomeni A., et al. Statin liver safety in non-alcoholic fatty liver disease: A systematic review and metanalysis. Br J Clin Pharmacol. 2022;88(2):441–51. DOI: 10.1111/bcp.14943

264. Abdallah M., Brown L., Provenza J., Tariq R., Gowda S., Singal A.K. Safety and efficacy of dyslipidemia treatment in NAFLD patients: A meta-analysis of randomized controlled trials. Ann Hepatol. 2022;27(6):100738. DOI: 10.1016/j.aohep.2022.100738

265. Athyros V.G., Boutari C., Stavropoulos K., Anagnostis P., Imprialos K.P., Doumas M., et al. Statins: An under-appreciated asset for the prevention and the treatment of NAFLD or NASH and the related cardiovascular risk. Curr Vasc Pharmacol. 2018;16(3):246–53. DOI: 10.2174/1570161115666170621082910

266. Torres-Peña J.D., Martín-Piedra L., Fuentes-Jiménez F. Statins in non-alcoholic steatohepatitis. Front Cardiovasc Med. 2021;8:777131. DOI: 10.3389/fcvm.2021.777131

267. Aithal G.P., Watkins P.B., Andrade R.J., Larrey D., Molokhia M., Takikawa H., et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89(6):806–15. DOI: 10.1038/clpt.2011.58

268. Martsevich S.Yu., Kutishenko N.P., Drozdova L.Yu., Lerman O.V., Nevzorova V.A., Reznik I.I., et al. Ursodeoxycholic acid-enhanced efficiency and safety of statin therapy in patients with liver, gallbladder, and/or biliary tract diseases: The RACURS study. Terapevticheskii Arkhiv. 2014;86(12):48–52. (In Russ.). DOI: 10.17116/terarkh2014861248-52

269. Nadinskaya M., Martsevich S., Kutishenko N., Balashov I., Lerman O. P0624 Ursodeoxycholic acid influence on efficacy and safety of statin therapy in patients with high risk of cardiovascular events and nonalcoholic fatty liver disease: The RACURS study (post-hoc analysis). United European Gastroenterol J. 2015;3(Suppl. 5):P0624. DOI: 10.1177/2050640615601623

270. Cabezas Gelabert R. Effect of ursodeoxycholic acid combined with statins in hypercholesterolemia treatment: A prospective clinical trial. Rev Clin Esp. 2004;204(12):632–5. (In Spanish). DOI: 10.1016/s0014-2565(04)71566-0

271. Seo S.H., Lee D.H., Lee Y.S., Cho K.J., Park H.J., Lee H.W., et al. Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model. Gastroenterol Rep (Oxf). 2022;10:goac037. DOI: 10.1093/gastro/goac037

272. Nakade Y., Murotani K., Inoue T., Kobayashi Y., Yamamoto T., Ishii N., et al. Ezetimibe for the treatment of non-alcoholic fatty liver disease: A meta-analysis. Hepatol Res. 2017;47(13):1417–28. DOI: 10.1111/hepr.12887

273. Lee H.Y., Jun D.W., Kim H.J., Oh H., Saeed W.K., Ahn H., et al. Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis. Korean J Intern Med. 2019;34(2):296–304. DOI: 10.3904/kjim.2017.194

274. Cho Y., Rhee H., Kim Y.E., Lee M., Lee B.W., Kang E.S., et al. Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: An open-label randomized controlled trial (ESSENTIAL study). BMC Med. 2022;20(1):93. DOI: 10.1186/s12916-022-02288-2

275. Scorletti E., Bhatia L., McCormick K.G., Clough G.F., Nash K., Hodson L., et al. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: Results from the Welcome* study. Hepatology. 2014;60(4):1211–21. DOI: 10.1002/hep.27289

276. Maciejewska-Markiewicz D., Stachowska E., Hawryłkowicz V., Stachowska L., Prowans P. The role of resolvins, protectins and marensins in non-alcoholic fatty liver disease (NAFLD). Biomolecules. 2021;11(7):937. DOI: 10.3390/biom11070937

277. Bhatt D.L., Steg P.G., Miller M., Brinton E.A., Jacobson T.A., Ketchum S.B., et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22. DOI: 10.1056/NEJMoa1812792

278. Sanyal A.J., Abdelmalek M.F., Suzuki A., Cummings O.W., Chojkier M. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology. 2014;147(2):377–84.e1. DOI: 10.1053/j.gastro.2014.04.046

279. Lee C.H., Fu Y., Yang S.J., Chi C.C. Effects of omega-3 polyunsaturated fatty acid supplementation on non-alcoholic fatty liver: A systematic review and meta-analysis. Nutrients. 2020;12(9):2769. DOI: 10.3390/nu12092769

280. Musazadeh V., Karimi A., Malekahmadi M., Ahrabi S.S., Dehghan P. Omega-3 polyunsaturated fatty acids in the treatment of non-alcoholic fatty liver disease: An umbrella systematic review and meta-analysis. Clin Exp Pharmacol Physiol. 2023;50(5):327–34. DOI: 10.1111/1440-1681.13750

281. Yan J.H., Guan B.J., Gao H.Y., Peng X.E. Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018;97(37):e12271. DOI: 10.1097/MD.0000000000012271

282. Hilleman D.E., Wiggins B.S., Bottorff M.B. Critical differences between dietary supplement and prescription omega-3 fatty acids: A narrative review. Adv Ther. 2020;37(2):656–70. DOI: 10.1007/s12325-019-01211-1

283. Fernández-Miranda C., Pérez-Carreras M., Colina F., López-Alonso G., Vargas C., Solís-Herruzo J.A. A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis. 2008;40(3):200–5. DOI: 10.1016/j.dld.2007.10.002

284. Mahmoudi A., Moallem S.A., Johnston T.P., Sahebkar A. Liver protective effect of fenofibrate in NASH/NAFLD animal models. PPAR Res. 2022;2022:5805398. DOI: 10.1155/2022/5805398

285. Lawitz E.J., Bhandari B.R., Ruane P.J., Kohli A., Harting E., Ding D., et al. Fenofibrate mitigates hypertriglyceridemia in nonalcoholic steatohepatitis patients treated with cilofexor/firsocostat. Clin Gastroenterol Hepatol. 2023;21(1):143–52.e3. DOI: 10.1016/j.cgh.2021.12.044

286. Maev I.V., Samsonov A.A., Palgova L.K., Pavlov C.S., Shirokova E.N., Vovk E.I., et al. Effectiveness of phosphatidylcholine as adjunctive therapy in improving liver function tests in patients with non-alcoholic fatty liver disease and metabolic comorbidities: Real-life observational study from Russia. BMJ Open Gastroenterol. 2020;7(1):e000368. DOI: 10.1136/bmjgast-2019-000368

287. Dajani A.I, Popovic B. Essential phospholipids for nonalcoholic fatty liver disease associated with metabolic syndrome: A systematic review and network meta-analysis. World J Clin Cases. 2020;8(21):5235–49. DOI: 10.12998/wjcc.v8.i21.5235

288. Kuche K., Bhargavi N., Dora C.P., Jain S. Drug-phospholipid complex — a go through strategy for enhanced oral bioavailability. AAPS PharmSciTech. 2019;20(2):43. DOI: 10.1208/s12249-018-1252-4

289. Okovityi S.V., Bolotova V.Ts., Anisimova N.A., Ivkin D.Yu., Titovich I.A., Sysoev Yu.I., et al. Prospects for using plant extracts to correct fat and carbohydrate metabolism disorders. Pharmacy. 2020;69(2):17–22. (In Russ.). DOI: 10.29296/25419218-2020-02-03

290. Dimakopoulou A., Sfikas G., Athyros V. PCSK9 administration ameliorates non alcoholic fatty disease in patients with heterozygous familial hyperlipidemia. Hell J Atheroscler. 2018;9(2):12. DOI: 10.23803/HJA.V9I2.175.G150

291. Rimbert A., Smati S., Dijk W., Le May C., Cariou B. Genetic inhibition of PCSK9 and liver function. JAMA Cardiol. 2021;6(3):353–4. DOI: 10.1001/jamacardio.2020.5341

292. Jang H.R., Kang D., Sinn D.H., Gu S., Cho S.J., Lee J.E., et al. Nonalcoholic fatty liver disease accelerates kidney function decline in patients with chronic kidney disease: A cohort study. Sci Rep. 2018;8(1):4718. DOI: 10.1038/s41598-018-23014-0

293. Musso G., Gambino R., Tabibian J.H., Ekstedt M., Kechagias S., Hamaguchi M., et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: A systematic review and meta-analysis. PLoS Med. 2014;11(7):e1001680. DOI: 10.1371/journal.pmed.1001680

294. Targher G., Chonchol M., Bertolini L., Rodella S., Zenari L., Lippi G., et al. Increased risk of CKD among type 2 diabetics with nonalcoholic fatty liver disease. J Am Soc Nephrol. 2008;19(8):1564–70. DOI: 10.1681/ASN.2007101155

295. Heda R., Yazawa M., Shi M., Bhaskaran M., Aloor F.Z., Thuluvath P.J., et al. Non-alcoholic fatty liver and chronic kidney disease: Retrospect, introspect, and prospect. World J Gastroenterol. 2021;27(17):1864–82. DOI: 10.3748/wjg.v27.i17.1864

296. Monteillet L., Gjorgjieva M., Silva M., Verzieux V., Imikirene L., Duchampt A., et al. Intracellular lipids are an independent cause of liver injury and chronic kidney disease in non alcoholic fatty liver disease-like context. Mol Metab. 2018;16:100–15. DOI: 10.1016/j.molmet.2018.07.006

297. Shimano H., Sato R. SREBP-regulated lipid metabolism: Convergent physiology — divergent pathophysiology. Nat Rev Endocrinol. 2017;13(12):710–30. DOI: 10.1038/nrendo.2017.91

298. Marcuccilli M., Chonchol M. NAFLD and chronic kidney disease. Int J Mol Sci. 2016;17(4):562. DOI: 10.3390/ijms17040562

299. Kwon S.Y., Park J., Park S.H., Lee Y.B., Kim G., Hur K.Y., et al. MAFLD and NAFLD in the prediction of incident chronic kidney disease. Sci Rep. 2023;13(1):1796. DOI: 10.1038/s41598-023-27762-6

300. Zhang X., Wong G.L., Yip T.C., Tse Y.K., Liang L.Y., Hui V.W., et al. Angiotensin-converting enzyme inhibitors prevent liver-related events in nonalcoholic fatty liver disease. Hepatology. 2022;76(2):469–82. DOI: 10.1002/hep.32294

301. Hirata T., Tomita K., Kawai T., Yokoyama H., Shimada A., Kikuchi M., et al. Effect of telmisartan or losartan for treatment of nonalcoholic fatty liver disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY). Int J Endocrinol. 2013:587140. DOI: 10.1155/2013/587140

302. Georgescu E.F., Georgescu M. Therapeutic options in non-alcoholic steatohepatitis (NASH). Are all agents alike? Results of a preliminary study. J Gastrointestin Liver Dis. 2007;16(1):39–46.

303. Georgescu E.F., Ionescu R., Niculescu M., Mogoanta L., Vancica L. Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis. World J Gastroenterol. 2009;15(8):942–54. DOI: 10.3748/wjg.15.942

304. Yokohama S., Yoneda M., Haneda M., Okamoto S., Okada M., Aso K., et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004;40(5):1222–5. DOI: 10.1002/hep.20420

305. Osterreicher C.H., Taura K., De Minicis S., Seki E., Penz-Osterreicher M., Kodama Y., et al. Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice. Hepatology. 2009;50(3):929–38. DOI: 10.1002/hep.23104

306. Ala M. SGLT2 inhibition for cardiovascular diseases, chronic kidney disease, and NAFLD. Endocrinology. 2021;162(12):bqab157. DOI: 10.1210/endocr/bqab157

307. Toyama T., Neuen B.L., Jun M., Ohkuma T., Neal B., Jardine M.J., et al. Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta-analysis. Diabetes Obes Metab. 2019;21(5):1237–50. DOI: 10.1111/dom.13648

308. Sarafidis P., Ferro C.J., Morales E., Ortiz A., Malyszko J., Hojs R., et al. SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease. A consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA. Nephrol Dial Transplant. 2019;34(2):208–30. DOI: 10.1093/ndt/gfy407

309. Musso G., Cassader M., Cohney S., De Michieli F., Pinach S., Saba F., et al. Fatty liver and chronic kidney disease: Novel mechanistic insights and therapeutic opportunities. Diabetes Care. 2016;39(10):1830–45. DOI: 10.2337/dc15-1182

310. Heerspink H.J.L., Stefánsson B.V., Correa-Rotter R., Chertow G.M., Greene T., Hou F.F., et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46. DOI: 10.1056/NEJMoa2024816

311. Herrington W.G., Staplin N., Wanner C., Green J.B., Hauske S.J., Emberson J.R., et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117–27. DOI: 10.1056/NEJMoa2204233

312. Palmer S.C., Tendal B., Mustafa R.A., Vandvik P.O., Li S., Hao Q., et al. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: Systematic review and network meta-analysis of randomised controlled trials. BMJ. 2021;372:m4573. DOI: 10.1136/bmj.m4573

313. Greco E.V., Russo G., Giandalia A., Viazzi F., Pontremoli R., De Cosmo S. GLP-1 receptor agonists and kidney protection. Medicina (Kaunas). 2019;55(6):233. DOI: 10.3390/medicina55060233

314. Marso S.P., Daniels G.H., Brown-Frandsen K., Kristensen P., Mann J.F., Nauck M.A., et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. DOI: 10.1056/NEJMoa1603827

315. Marso S.P., Bain S.C., Consoli A., Eliaschewitz F.G., Jódar E., Leiter L.A., et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44. DOI: 10.1056/NEJMoa1607141

316. Gerstein H.C., Colhoun H.M., Dagenais G.R., Diaz R., Lakshmanan M., Pais P., et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121–30. DOI: 10.1016/S0140-6736(19)31149-3

317. Zhang Y., Jiang L., Wang J., Wang T., Chien C., Huang W., et al. Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease. Cardiovasc Diabetol. 2022;21(1):232. DOI: 10.1186/s12933-022-01676-5

318. Ludwig J., Viggiano T.R., McGill D.B., Oh B.J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55(7):434–8.

319. Powell E.E., Cooksley W.G., Hanson R., Searle J., Halliday J.W., Powell L.W. The natural history of nonalcoholic steatohepatitis: A follow-up study of forty-two patients for up to 21 years. Hepatology. 1990;11(1):74–80. DOI: 10.1002/hep.1840110114

320. Ajmera V., Belt P., Wilson L.A., Gill R.M., Loomba R., Kleiner D.E., et al. Among patients with nonalcoholic fatty liver disease, modest alcohol use is associated with less improvement in histologic steatosis and steatohepatitis. Clin Gastroenterol Hepatol. 2018;16(9):1511–20.e5. DOI: 10.1016/j.cgh.2018.01.026

321. Kimura T., Tanaka N., Fujimori N., Sugiura A., Yamazaki T., Joshita S., et al. Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis. World J Gastroenterol. 2018;24(13):1440–50. DOI: 10.3748/wjg.v24.i13.1440

322. Younossi Z.M., Stepanova M., Ong J., Yilmaz Y., Duseja A., Eguchi Y., et al. Effects of alcohol consumption and metabolic syndrome on mortality in patients with nonalcoholic and alcohol-related fatty liver disease. Clin Gastroenterol Hepatol. 2019;17(8):1625–33.e1. DOI: 10.1016/j.cgh.2018.11.033

323. Ekstedt M., Franzén L.E., Holmqvist M., Bendtsen P., Mathiesen U.L., Bodemar G., et al. Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease. Scand J Gastroenterol. 2009;44(3):366–74. DOI: 10.1080/00365520802555991

324. Sookoian S., Castaño G.O., Pirola C.J. Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: A meta-analysis of 43,175 individuals. Gut. 2014;63(3):530–2. DOI: 10.1136/gutjnl-2013-305718

325. Cao G., Yi T., Liu Q., Wang M., Tang S. Alcohol consumption and risk of fatty liver disease: A meta-analysis. PeerJ. 2016;4:e2633. DOI: 10.7717/peerj.2633

326. Chang Y., Cho Y.K., Kim Y., Sung E., Ahn J., Jung H.S., et al. Nonheavy drinking and worsening of noninvasive fibrosis markers in nonalcoholic fatty liver disease: A cohort study. Hepatology. 2019;69(1):64–75. DOI: 10.1002/hep.30170

327. Blomdahl J., Nasr P., Ekstedt M., Kechagias S. Moderate alcohol consumption is associated with significant fibrosis progression in NAFLD. Hepatol Commun. 2023;7(1):e0003. DOI: 10.1097/HC9.0000000000000003

328. Ivashkin V.T., Zharkova M.S., Korochanskaya N.V., Khlynov I.B., Uspensky Yu.P. Phenotypes of non-alcoholic fatty liver disease in different regions of the Russian Federation, diagnostic and therapeutic approach in clinical practice. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2023;33(2):7–18. (In Russ.). DOI: 10.22416/1382-4376-2023-33-2-7-18

329. Mato J.M., Cámara J., Fernández de Paz J., Caballería L., Coll S., Caballero A., et al. S-adenosylmethionine in alcoholic liver cirrhosis: A randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30(6):1081–9. DOI: 10.1016/s0168-8278(99)80263-3

330. Rambaldi A., Gluud C. S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Syst Rev. 2006;2:CD002235. DOI: 10.1002/14651858.CD002235.pub2

331. Lassailly G., Caiazzo R., Buob D., Pigeyre M., Verkindt H., Labreuche J., et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379–88. DOI: 10.1053/j.gastro.2015.04.014

332. Bower G., Toma T., Harling L., Jiao L.R., Efthimiou E., Darzi A., et al. Bariatric surgery and non-alcoholic fatty liver disease: A systematic review of liver biochemistry and histology. Obes Surg. 2015;25(12):2280–9. DOI: 10.1007/s11695-015-1691-x

333. Lee Y., Doumouras A.G., Yu J., Brar K., Banfield L., Gmora S., et al. Complete resolution of nonalcoholic fatty liver disease after bariatric surgery: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17(6):1040–60.e11. DOI: 10.1016/j.cgh.2018.10.017

334. Fakhry T.K., Mhaskar R., Schwitalla T., Muradova E., Gonzalvo J.P., Murr M.M. Bariatric surgery improves nonalcoholic fatty liver disease: A contemporary systematic review and meta-analysis. Surg Obes Relat Dis. 2019;15(3):502–11. DOI: 10.1016/j.soard.2018.12.002

335. Zhou H., Luo P., Li P., Wang G., Yi X., Fu Z., et al. Bariatric surgery improves nonalcoholic fatty liver disease: Systematic review and meta-analysis. Obes Surg. 2022;32(6):1872–83. DOI: 10.1007/s11695-022-06011-1

336. Lazarus J.V., Mark H.E., Anstee Q.M., Arab J.P., Batterham R.L., Castera L., et al. Advancing the global public health agenda for NAFLD: A consensus statement. Nat Rev Gastroenterol Hepatol. 2022;19(1):60–78. DOI: 10.1038/s41575-021-00523-4

337. 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 for the management of non-alcoholic fatty liver disease. Obes Facts. 2016;9(2):65–90. DOI: 10.1159/000443344

338. Fernández T., Viñuela M., Vidal C., Barrera F. Lifestyle changes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. PLoS One. 2022;17(2):e0263931. DOI: 10.1371/journal.pone.0263931

339. Glass L.M., Hunt C.M., Fuchs M., Su G.L. Comorbidities and nonalcoholic fatty liver disease: The chicken, the egg, or both? Fed Pract. 2019;36(2):64–71.

340. Singh S., Singh P.P., Singh A.G., Murad M.H., Sanchez W. Anti-diabetic medications and the risk of hepatocellular cancer: A systematic review and meta-analysis. Am J Gastroenterol. 2013;108(6):881–91. DOI: 10.1038/ajg.2013.5

341. Ma S., Zheng Y., Xiao Y., Zhou P., Tan H. Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients. Medicine (Baltimore). 2017;96(19):e6888. DOI: 10.1097/MD.0000000000006888

342. Zhou Y.Y., Zhu G.Q., Liu T., Zheng J.N., Cheng Z., Zou T.T., et al. Systematic review with network meta-analysis: Antidiabetic medication and risk of hepatocellular carcinoma. Sci Rep. 2016;6:33743. DOI: 10.1038/srep33743

343. Singh S., Singh P.P., Singh A.G., Murad M.H., Sanchez W. Statins are associated with a reduced risk of hepatocellular cancer: A systematic review and meta-analysis. Gastroenterology. 2013;144(2):323–32. DOI: 10.1053/j.gastro.2012.10.005

344. Singal A., Volk M.L., Waljee A., Salgia R., Higgins P., Rogers M.A., et al. Meta-analysis: Surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30(1):37–47. DOI: 10.1111/j.1365-2036.2009.04014.x

345. European Association for the Study of the Liver. EASL clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. DOI: 10.1016/j.jhep.2018.03.019

346. Machado M.V. The growing landscape of NAFLD-associated hepatocellular carcinoma and its impact in surveillance. GE Port J Gastroenterol. 2023;31(1):14–23. DOI: 10.1159/000531397

347. Younossi Z., Stepanova M., Ong J.P., Jacobson I.M., Bugianesi E., Duseja A., et al. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol. 2019;17(4):748–55.e3. DOI: 10.1016/j.cgh.2018.05.057

348. Ducreux M., Abou-Alfa G.K., Bekaii-Saab T., Berlin J., Cervantes A., de Baere T., et al. The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022. ESMO Open. 2023;8(3):101567. DOI: 10.1016/j.esmoop.2023.101567

349. Adams L.A., Lymp J.F., St Sauver J., Sanderson S.O., Lindor K.D., Feldstein A., et al. The natural history of nonalcoholic fatty liver disease: A population-based cohort study. Gastroenterology. 2005;129(1):113–21. DOI: 10.1053/j.gastro.2005.04.014

350. Hashimoto E., Yatsuji S., Tobari M., Taniai M., Torii N., Tokushige K., et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol. 2009;44(Suppl. 19):89–95. DOI: 10.1007/s00535-008-2262-x

351. Ascha M.S., Hanouneh I.A., Lopez R., Tamimi T.A., Feldstein A.F., Zein N.N. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51(6):1972–8. DOI: 10.1002/hep.23527

352. Bertot L.C., Jeffrey G.P., Wallace M., MacQuillan G., Garas G., Ching H.L., et al. Nonalcoholic fatty liver disease-related cirrhosis is commonly unrecognized and associated with hepatocellular carcinoma. Hepatol Commun. 2017;1(1):53–60. DOI: 10.1002/hep4.1018

353. Than N.N., Ghazanfar A., Hodson J., Tehami N., Coldham C., Mergental H., et al. Comparing clinical presentations, treatments and outcomes of hepatocellular carcinoma due to hepatitis C and non-alcoholic fatty liver disease. QJM. 2017;110(2):73–81. DOI: 10.1093/qjmed/hcw151

354. Yoo J.J., Park M.Y., Cho E.J., Yu S.J., Kim S.G., Kim Y.J., et al. Smoking increases the risk of hepatocellular carcinoma and cardiovascular disease in patients with metabolic-associated fatty liver disease. J Clin Med. 2023;12(9):3336. DOI: 10.3390/jcm12093336

355. Caussy C., Soni M., Cui J., Bettencourt R., Schork N., Chen C.H., et al. Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis. J Clin Invest. 2017;127(7):2697–704. DOI: 10.1172/JCI93465

356. Wijarnpreecha K., Thongprayoon C., Ungprasert P. Coffee consumption and risk of nonalcoholic fatty liver disease: A systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2017;29(2):e8–12. DOI: 10.1097/MEG.0000000000000776

357. Hayat U., Siddiqui A.A., Okut H., Afroz S., Tasleem S., Haris A. The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: A meta-analysis of 11 epidemiological studies. Ann Hepatol. 2021;20:100254. DOI: 10.1016/j.aohep.2020.08.071

358. Kennedy O.J., Roderick P., Buchanan R., Fallowfield J.A., Hayes P.C., Parkes J. Coffee, including caffeinated and decaffeinated coffee, and the risk of hepatocellular carcinoma: A systematic review and dose-response meta-analysis. BMJ Open. 2017;7(5):e013739. DOI: 10.1136/bmjopen-2016-013739

359. Shen H., Rodriguez A.C., Shiani A., Lipka S., Shahzad G., Kumar A., et al. Association between caffeine consumption and nonalcoholic fatty liver disease: A systemic review and meta-analysis. Therap Adv Gastroenterol. 2016;9(1):113–20. DOI: 10.1177/1756283X15593700

360. Chen Y.P., Lu F.B., Hu Y.B., Xu L.M., Zheng M.H., Hu E.D. A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease. Clin Nutr. 2019;38(6):2552–7. DOI: 10.1016/j.clnu.2018.11.030

361. Marventano S., Salomone F., Godos J., Pluchinotta F., Del Rio D., Mistretta A., et al. Coffee and tea consumption in relation with non-alcoholic fatty liver and metabolic syndrome: A systematic review and meta-analysis of observational studies. Clin Nutr. 2016;35(6):1269–81. DOI: 10.1016/j.clnu.2016.03.012

362. Ebadi M., Ip S., Bhanji R.A., Montano-Loza A.J. Effect of coffee consumption on non-alcoholic fatty liver disease incidence, prevalence and risk of significant liver fibrosis: Systematic review with meta-analysis of observational studies. Nutrients. 2021;13(9):3042. DOI: 10.3390/nu13093042

363. Birerdinc A., Stepanova M., Pawloski L., Younossi Z.M. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2012;35(1):76–82. DOI: 10.1111/j.1365-2036.2011.04916.x

364. Inoue M., Yoshimi I., Sobue T., Tsugane S. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: A prospective study in Japan. J Natl Cancer Inst. 2005;97(4):293–300. DOI: 10.1093/jnci/dji040

365. Johnson S., Koh W.P., Wang R., Govindarajan S., Yu M.C., Yuan J.M. Coffee consumption and reduced risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study. Cancer Causes Control. 2011;22(3):503–10. DOI: 10.1007/s10552-010-9725-0

366. Hu G., Tuomilehto J., Pukkala E., Hakulinen T., Antikainen R., Vartiainen E., et al. Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer. Hepatology. 2008;48(1):129–36. DOI: 10.1002/hep.22320

367. Tanaka K., Hara M., Sakamoto T., Higaki Y., Mizuta T., Eguchi Y., et al. Inverse association between coffee drinking and the risk of hepatocellular carcinoma: A case-control study in Japan. Cancer Sci. 2007;98(2):214–8. DOI: 10.1111/j.1349-7006.2006.00368.x