Клинические рекомендации Российского общества по изучению печени, Российской гастроэнтерологической ассоциации, Российской ассоциации эндокринологов, Российской ассоциации геронтологов и гериатров и Национального общества профилактической кардиологии по диагностике и лечению неалкогольной жировой болезни печени
https://doi.org/10.22416/1382-4376-2022-32-4-104-140
Аннотация
Цель: в клинических рекомендациях, предназначенных для врачей общей практики, врачей-терапевтов, врачей-гастроэнтерологов, врачей-кардиологов, врачей-эндокринологов, представлены современные методы диагностики и лечения неалкогольной жировой болезни печени.
Основное содержание. Неалкогольная жировая болезнь печени — самое частое хроническое заболевание печени, при котором более 5 % гепатоцитов аккумулирует жир, представлено двумя гистологическими формами: стеатоз и неалкогольный стеатогепатит. В клинических рекомендациях описаны современные представления о патогенезе неалкогольной жировой болезни печени как мультисистемного заболевания, методы инвазивной и неинвазивной диагностики стеатоза и фиброза печени, принципы немедикаментозного лечения и фармакотерапии неалкогольной жировой болезни печени и ассоциированных с ней состояний. Представлены осложнения неалкогольной жировой болезни печени, такие как усугубление кардиометаболических рисков, развитие гепатоцеллюлярного рака, прогрессия фиброза печени до стадии цирроза.
Заключение. При своевременной диагностике неалкогольной жировой болезни печени и ассоциированных коморбидных состояний, грамотном междисциплинарном ведении этих пациентов можно избежать прогрессии заболевания печени и уменьшить кардиометаболические риски, улучшить жизненный прогноз пациентов.
Об авторах
В. Т. ИвашкинРоссия
Ивашкин Владимир Трофимович — доктор медицинских наук, академик РАН, профессор, заведующий кафедрой пропедевтики внутренних болезней, гастроэнтерологии и гепатологии
119435, г. Москва, ул. Погодинская, д. 1, стр. 1
М. В. Маевская
Россия
Маевская Марина Викторовна — доктор медицинских наук, профессор
119435, г. Москва, ул. Погодинская, д. 1, стр. 1
М. С. Жаркова
Россия
Жаркова Мария Сергеевна — кандидат медицинских наук, заведующая отделением гепатологии Клиники пропедевтики внутренних болезней, гастроэнтерологии, гепатологии им. В.Х. Василенко
119435, г. Москва, ул. Погодинская, д. 1, стр. 1
Ю. В. Котовская
Россия
Котовская Юлия Викторовна — доктор медицинских наук, профессор, заместитель директора по научной работе
129226, г. Москва, ул. 1-я Леонова, д. 16
О. Н. Ткачева
Россия
Ткачева Ольга Николаевна — доктор медицинских наук,
профессор, директор
129226, г. Москва, ул. 1-я Леонова, д. 16
Е. А. Трошина
Россия
Трошина Екатерина Анатольевна — доктор медицинских
наук, профессор, член-корреспондент РАН, заместитель
директора, директор Института клинической эндокринологии
117292, г. Москва, ул. Дмитрия Ульянова, д. 11
М. В. Шестакова
Россия
Шестакова Марина Владимировна — академик РАН, доктор медицинских наук, профессор, заместитель директора, директор Института диабета
117292, г. Москва, ул. Дмитрия Ульянова, д. 11
И. В. Маев
Россия
Маев Игорь Вениаминович — доктор медицинских наук, академик РАН, профессор, заведующий кафедрой пропедевтики внутренних болезней и гастроэнтерологии
127473, г. Москва, ул. Делегатская, д. 20, стр. 1
В. В. Бредер
Россия
Бредер Валерий Владимирович — доктор медицинских наук, ведущий научный сотрудник, онкологическое отделение лекарственных методов лечения (химиотерапевтическое отделение № 17)
115478, г. Москва, Каширское шоссе, д. 23
Н. И. Гейвандова
Россия
Гейвандова Наталья Иогановна — доктор медицинских наук, профессор кафедры госпитальной терапии
355017, г. Ставрополь, ул. Мира, д. 310
В. Л. Дощицин
Россия
Дощицин Владимир Леонидович — доктор медицинских наук, профессор кафедры кардиологии ФДПО
117997, г. Москва, ул. Островитянова, д. 1
Е. Н. Дудинская
Россия
Дудинская Екатерина Наильевна — кандидат медицинских наук, заведующая лабораторией возрастных метаболических эндокринных нарушений
129226, г. Москва, ул. 1-я Леонова, д. 16
Е. В. Ершова
Россия
Ершова Екатерина Владимировна — кандидат медицинских наук, ведущий научный сотрудник отделения терапевтической эндокринологии
117292, г. Москва, ул. Дмитрия Ульянова, д. 11
Х. Б. Кодзоева
Россия
Кодзоева Хава Багаудиновна — аспирант кафедры пропедевтики внутренних болезней, гастроэнтерологии и гепатологии Института клинической медицины им. Н.В. Склифосовского
119435, г. Москва, ул. Погодинская, д. 1, стр. 1
К. А. Комшилова
Россия
Комшилова Ксения Андреевна — кандидат медицинских наук, врач-эндокринолог отделения терапевтической эндокринологии
117292, г. Москва, ул. Дмитрия Ульянова, д. 11
Н. В. Корочанская
Россия
Корочанская Наталья Всеволодовна — доктор медицинских наук, профессор кафедры хирургии № 3 ФПК и ППС
350063, г. Краснодар, ул. Митрофана Седина, д. 4
А. Ю. Майоров
Россия
Майоров Александр Юрьевич — доктор медицинских наук,
заведующий отделением прогнозирования и инноваций диабета, профессор кафедры диабетологии и диетологии
117292, г. Москва, ул. Дмитрия Ульянова, д. 11
Е. Е. Мишина
Россия
Мишина Екатерина Евгеньевна — научный сотрудник отделения прогнозирования и инноваций диабета
117292, г. Москва, ул. Дмитрия Ульянова, д. 11
М. Ю. Надинская
Россия
Надинская Мария Юрьевна — кандидат медицинских наук,
доцент кафедры пропедевтики внутренних болезней, гастроэнтерологии и гепатологии Института клинической медицины им. Н.В. Склифосовского
119435, г. Москва, ул. Погодинская, д. 1, стр. 1
И. Г. Никитин
Россия
Никитин Игорь Геннадьевич — доктор медицинских наук, профессор, заведующий кафедрой госпитальной терапии № 2 лечебного факультета; директор ФГАУ НМИЦ «Лечебно-реабилитационный центр»
117997, г. Москва, ул. Островитянова, д. 1
Н. В. Погосова
Россия
Погосова Нана Вачиковна — доктор медицинских наук, профессор, заместитель генерального директора по научно-аналитической работе и профилактической кардиологии
121552, г. Москва, ул. 3-я Черепковская, д. 15а, стр. 1
А. И. Тарзиманова
Россия
Тарзиманова Аида Ильгизовна — доктор медицинских наук,
профессор кафедры факультетской терапии № 2
119048, г. Москва, ул. Ефремова, д. 24
М. Ш. Шамхалова
Россия
Шахмалова Минара Шахмаловна — доктор медицинских наук, заведующая отделением диабетической болезни почек и посттрансплантационной реабилитации
117292, г. Москва, ул. Дмитрия Ульянова, д. 11
Список литературы
1. Kleiner D.E., Makhlouf H.R. Histology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in Adults and Children. Clin Liver Dis. 2016;20(2):293–312. DOI: 10.1016/j.cld.2015.10.011
2. Day C.P., James O.F. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–5. DOI: 10.1016/s0016-5085(98)70599-2
3. Byrne C.D., Targher G. NAFLD: A multisystem disease. J Hepatol. 2015;62(1S):S47–S64. DOI: 10.1016/j.jhep.2014.12.012
4. 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;24:2974–83. DOI: 10.3748/wjg.v24.i27.2974
5. Xian Y.X., Weng J.P., Xu F. MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy. Chin Med J. 2020;134:8–19. DOI: 10.1097/CM9.0000000000001263
6. Parthasarathy G., Revelo X., Malhi H. Pathogenesis of Nonalcoholic Steatohepatitis: An Overview. Hepatology Communications. 2020;4(4):478–92. DOI: 10.1002/hep4.1479
7. 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
8. Friedman J. Leptin at 20: an overview. J Endocrinol. 2014;223:1–T8. DOI: 10.1530/JOE-14-0405
9. Samuel V.T., Shulman G.I. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016;126:12–22. DOI: 10.1172/JCI77812
10. 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;75:3313–27. DOI: 10.1007/s00018-018-2860-6
11. 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;146:726–35. DOI: 10.1053/j.gastro.2013.11.049
12. 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
13. Basaranoglu M., Basaranoglu G., Bugianesi E. Carbohydrate intake and nonalcoholic fatty liver disease: Fructose as a weapon of mass destruction. Hepatobiliary Surg Nutr. 2015;4:109–16. DOI: 10.3978/j.issn.2304-3881.2014.11.05
14. Jensen T., Abdelmalek M.F., Sullivan S., Kristen J Nadeau K.J., Green M., Roncal C., et al. Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. J Hepatol. 2018;68:1063–75. DOI: 10.1016/j.jhep.2018.01.019
15. Birkenfeld A.L., Shulman G.I. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology. 2014;59:713–23. DOI: 10.1002/hep.26672
16. Ghorpade D.S., Ozcan L., Zheng Z., NicoloroS.M., ShenY., Chenet E.,et al. Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature. 2018;555:673–77. DOI: 10.1038/nature26138
17. Ferramosca A., Zara V. Modulation of hepatic steatosis by dietary fatty acids. World J Gastroenterol. 2014;20:1746–55. DOI: 10.3748/wjg.v20.i7.1746
18. Malhi H., Gores G.J. Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:360–9. DOI: 10.1055/s-0028-1091980
19. Musso G., Cassader M., Paschetta E., Gambino R. Bioactive lipid species and metabolic pathways in progression and resolution of nonalcoholic steatohepatitis. Gastroenterology. 2018;155:282–302.e288. DOI: 10.1053/j.gastro.2018.06.031
20. Parry S.A., Rosqvist F., Mozes F.E., CornfieldT., Hutchinson M., Pichee M.-E., et al. Intrahepatic fat and postprandial glycemia increase after consumption of a diet enriched in saturated fat compared with free sugars. Diabetes Care. 2020;43:1134–41. DOI: 10.2337/dc19-2331
21. Драпкина О.М., Буеверов А.О. Неалкогольная жировая болезнь как мультидисциплинарная патология. М.: Видокс. 2019.
22. Buzzetti E., Pinzani M., Tsochatzis E.A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65:1038–48. DOI: 10.1016/j.metabol.2015.12.012
23. Шифф Ю.Р., Соррел М.Ф., Мэддрей У.С. Алкогольные, лекарственные, генетические и метаболические заболевания; пер. с англ. М.: ГЭОТАР-Медиа, 2011.
24. 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
25. 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
26. Utzschneider K., Kahn S. The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab. 2006;91(12):4753–61. DOI: 10.1210/jc.2006-0587
27. Targher G., Bertolini L., Scala L., Zoppini G., Zenari L., Falezza G. Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue. Diabet Med. 2005;22(10):1354–8. DOI: 10.1111/j.1464-5491.2005.01646.x
28. Diehl A.M., Li Z.P., Lin H.Z., Yang S.Q. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut. 2005;54(2):303–6. DOI: 10.1136/gut.2003.024935
29. Marchesini G., Bugianesi E., Forlani G., Cerrelli F., Lenzi M., Manini R., et al. Nonalcoholic fatty liver, steatohepatitis and the metabolic syndrome. Hepatology. 2003;37:917–23. DOI: 10.1053/jhep.2003.50161
30. Sasaki A., Nitta H., Otsuka K., Umemura A., Baba S., Obuchi T., et al. Vilstric surgery and non-alcoholic fatty liver disease: current and potential future treatments. Front Endocrinol. 2014;5:164. DOI: 10.3389/fendo.2014.00164
31. 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;77:1502–15. DOI: 10.1016/j.lfs.2005.04.004
32. 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;11:137–41. DOI: 10.1016/j.soard.2014.06.015
33. Stanton M.C., Chen S.-C., Jackson J.V., Rojas-Triana A., Kinsley D., Cui L.,et al. Inflammatory signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice. J Inflamm. 2011;8:8. DOI: 10.1186/1476-9255-8-8
34. Virtue S., Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the metabolic syndrome — an allostatic perspective. Biochim Biophys Acta. 2010;1801:338–49. DOI: 10.1016/j.bbalip.2009.12.006
35. Stojsavljevic S., Gomercic Palcic M., Virovic Jukic L., Duvnjak L.S., Duvnjak M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:18070–91. DOI: 10.3748/wjg.v20.i48.18070
36. Osborn O., Olefsky J.M. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18:363–74. DOI: 10.1038/nm.2627
37. Marra F., Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol. 2018;68:280–95. DOI: 10.1016/j.jhep.2017.11.014
38. Di Maira G., Pastore M., Marra F. Liver fibrosis in the context of nonalcoholic steatohepatitis: the role of adipokines. Minerva Gastroenterol Dietol. 2018;64:39–50. DOI: 10.23736/S1121-421X.17.02427-8
39. Remmerie A., Martens L., Scott C.L. Macrophage subsets in obesity, aligning the liver and adipose tissue. Front Endocrinol. 2020;11:259. DOI: 10.3389/fendo.2020.00259
40. Machado M.V., Cortez-Pinto H. Gut microbiota and nonalcoholic fatty liver disease. Ann Hepatol. 2012;11(4): 440–9. DOI: 10.1016/S1665-2681(19)31457-7
41. Anstee Q.M., Targher G., Day C.P. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10:330–44. DOI: 10.1038/nrgastro.2013.41
42. Thomson A.W., Knolle P.A. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol. 2010;10:753–66. DOI: 10.1038/nri2858
43. 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
44. Szabo G., Csak T. Inflammasomes in liver diseases. J Hepatol. 2012;57:642–54. DOI: 10.1016/j.jhep.2012.03.035
45. Luedde T., Schwabe R.F. NF-κB in the liver — linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2011;8:108–18. DOI: 10.1038/nrgastro.2010.213
46. 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;110:4077–85. DOI: 10.1182/blood-2007-02-073841
47. Tomita K., Tamiya G., Ando S., Chiyo T., Mizutani A., Kitamura N., 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;55:415–24. DOI: 10.1136/gut.2005.071118
48. 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;44:216–27. DOI: 10.1002/hep.21221
49. Ghazarian M., Revelo X.S., Nohr 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):7616. DOI: 10.1126/sciimmunol.aai7616
50. Плотникова Е.Ю., Грачева Т.Ю., Ержанова Е.А. Роль кишечной микрофлоры в формировании неалкогольной жировой болезни печени. Лечащий врач. 2017;2:32–8.
51. Poeta M., Pierri L., Vajro P. Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease. Children (Basel). 2017;4:66. DOI: 10.3390/children4080066
52. 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
53. 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
54. Zhang Y., Lee F.Y., Barrera G., Lee H., Vales C., Gonzalez F.J., et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci USA. 2006;103(4):1006–11. DOI: 10.1073/pnas.0506982103
55. Watanabe M., Houten S.M., Wang L., Moschetta A., Mangelsdorf D.J., Heyman R.A., et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest. 2004;113(10):1408–18. DOI: 10.1172/JCI21025
56. Parseus A., Sommer N., Sommer F., Caesar R., Molinaro A., Stahlman M., et al. Microbiota-induced obesity requires farnesoid X receptor. Gut. 2017;66(3):429–37. DOI: 10.1136/gutjnl-2015-310283
57. Van Nierop F.S., Scheltema M.J., Eggink H.M., Pols T.W., Sonne D.P., Knop F.K., et al. Clinical relevance of the bile acid receptor TGR5 in metabolism. Lancet Diabetes Endocrinol. 2017;5(3):224–33. DOI: 10.1016/S2213-8587(16)30155-3
58. Amir M., Czaja M.J. Autophagy in nonalcoholic steatohepatitis. Expert Rev Gastroenterol Hepatol. 2011;5(2):159–66. DOI: 10.1586/egh.11.4
59. Wu P., Zhao J., Guo Y., Yu Y., Wu X., Xiao H. Ursodeoxycholic acid alleviates nonalcoholic fatty liver disease by inhibiting apoptosis and improving autophagy via activating AMPK. Biochem Biophys Res Commun. 2020;27;529(3):834–8. DOI: 10.1016/j.bbrc.2020.05.128
60. Kurashima Y., Kiyono H. Mucosal ecological network of epithelium and immune cells for gut homeostasis and tissue healing. Annu Rev Immunol. 2017;35:119–47. DOI: 10.1146/annurev-immunol-051116-052424
61. Nevo S., Kadouri N., Abramson J. Tuft cells: From the mucosa to the thymus. Immunol Lett. 2019;210:1–9. DOI: 10.1016/j.imlet.2019.02.003
62. Turner J.R. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009;9:799–809. DOI: 10.1038/nri2653
63. Van Itallie C.M., Holmes J., Bridges A., Gookin J.L., Coccaro M.R., Proctor W., et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci. 2008;121:298–305. DOI: 10.1242/jcs.021485
64. 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;22:8078–93. DOI: 10.3748/wjg.v22.i36.8078
65. 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
66. Kapil S., Duseja A., Sharma B.K., Singla B., Chakraborti A., Das A., et al. Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2016;31(1):213–21. DOI: 10.1111/jgh.13058
67. Aхмедов В.А., Меликов Т.И. Генетические аспекты формирования неалкогольной жировой болезни печени. Лечащий врач. 2019;8:28–31.
68. Al-Serri A., Anstee Q.M., Valenti L., Nobili V., Leathart J.B.S., Dongiovanni P., et al. The sod2 c47t polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studie. J Hepatol. 2011;56(2):448–54. DOI: 10.1016/j.jhep.2011.05.029
69. Dongiovanni P., Romeo S., Valenti L. Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis. BioMed Research International. 2015;460190:10. DOI: 10.1155/2015/460190
70. Petersen K.F., Dufour S., Hariri A., Nelson-Williams C., Foo J.N., Zhang X.-M., et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med. 2010;362(12):1082–89. DOI: 10.1056/NEJMoa0907295
71. Sazci A., Akpinar G., Aygun C., Ergul E., Senturk O., Hulagu S. Association of apolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis. Dig Dis Sci. 2008;53(12):3218–24. DOI: 10.1007/s10620-008-0271-5
72. BasuRay S., Wang Y., Smagris E., Cohen J.C., Hobbs H.H. Accumulation of PNPLA3 on lipid droplets is the basis of associated hepatic steatosis. Proc Natl Acad Sci USA. 2019;116:9521–26. DOI: 10.1073/pnas.1901974116
73. Kotronen A., Johansson L.E., Johansson L.M., Westerbacka J., Hamsten A., Bergholm R., et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia. 2009;52(6):1056–60. DOI: 10.1007/s00125-009-1285-z
74. Kawaguchi T., Sumida Y., Umemura A., Matsuo K., Takahashi M., Takamura T., et al. Japan Study Group of Nonalcoholic Fatty Liver, Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese. PLoS One. 2012;7(6):e38322. DOI:10.1371/journal.pone.0038322
75. Zain S.M., Mohamed R., Mahadeva S., Cheah P.L., Rampal S., Basu R.C., et al. A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Hum Genet. 2012;131(7):1145–52. DOI: 10.1007/s00439-012-1141-y
76. Takeuchi Y., Ikeda F., Moritou Y., Hagihara H., Yasunaka T., Kuwaki K., et al. The impact of patatin-like phospholipase domaincontaining protein 3 polymorphism on hepatocellular carcinoma prognosis. J Gastroenterol. 2012;48(3):405–12. DOI: 0.1007/s00535-012-0647-3.
77. Musso G., Gambino R., De Michiel F., Durazzo M., Pagano G., Cassader M. Adiponectin gene polymorphisms modulate acute adiponectin response to dietary fat: possible pathogenetic role in NASH. Hepatology. 2008;47(4):1167–77. DOI: 10.1002/hep.22142
78. Li X.-L., Sui J.-Q., Lu L.-L., Zhang N.-N., Xu X., Dong Q.-Y., et al. Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease: a concise review. Lipids Health Dis. 2016;15:53. DOI: 10.1186/s12944-016-0221-8
79. Zhang C., Guo L., Guo X. Interaction of polymorphisms of Leptin receptor gene Gln223Arg, MnSOD9Ala/Val genes and smoking in nonalcoholic fatty liver disease. Wei Sheng Yan Jiu. 2014;43(5):724–31.
80. Jichitu A., Bungau S., Stanescu A.M.A., Vesca 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
81. Ивашкин В.Т., Маевская М.В., Павлов Ч.С., Тихонов И.Н., Широкова Е.Н., Буеверов А.О., и др. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016;26(2):24-42 DOI:10.22416/1382-4376-2016-26-2-24-42
82. Шархун О.О. Формирование кардиометаболических нарушений при НАЖБП, ассоциированной с инсулинорезистентностью: автореф. … дис. д-ра мед. наук. М., 2019
83. Комова А.Г., Маевская М.В., Ивашкин В.Т. Принципы эффективной диагностики диффузных заболеваний печени на амбулаторном этапе. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2014;24(5):36–41.
84. 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
85. 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
86. Lazo M., Clark J. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28(4):339–50. DOI: 10.1055/s-0028-1091978
87. Misra V., Khashab M., Chalasani N. Nonalcoholic Fatty Liver Disease and Cardiovascular Risk. Curr Gastroenterol Rep. 2009;11:50–5. DOI: 10.1007/s11894-009-0008-4
88. Stefan N., Kantartzis K., Haring H.-U. Causes and Metabolic Consequences of Fatty Liver. Endoc Rev. 2008;29(7):939–60. DOI: 10.1210/er.2008-0009
89. Musso G., Gambino R., Cassader M. Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obesity Reviews. 2010;11(6):430–45. DOI: 10.1111/j.1467-789X.2009.00657.x
90. Ong J.P., Younossi Z. M. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11:1–16. DOI: 10.1016/j.cld.2007.02.009
91. Leite N.C., Salles G.F., Araujo A.L.E., Villela-Nogueira C.A., Cardoso C.R.L. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009;29:113–9. DOI: 10.1111/j.1478-3231.2008.01718.x
92. Younossi Z. M., Koenig A.B., Abdelatif D., Fazel Y., Henry L., Wymer M. Global epidemiology of nonalcoholic fatty liver desease — Meta-analytic assessment of prevalence, incidence and outcomes. Hepatology. 2016;64(1):73–84. DOI: 10.1002/hep.28431
93. Corey K.E., Kartoun U., Zheng H., Shaw S.Y. Development and Validation of an Algorithm to Identify Nonalcoholic Fatty Liver Disease in the Electronic Medical Record. Dig Dis Sci. 2016;61:913–9. DOI: 10.1007/s10620-015-3952-x
94. Targher G., Byrne C.D. Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease. Nat Rev Nephrol. 2017;13:297–310. DOI: 10.1038/nrneph.2017.16
95. Musso G., Gambino R., Tabibian J.H., Eksedt 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
96. Mantovani A., Zaza G., Byrne C.D., Byrne C.D., Lonardo A., Zoppini G., et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and metaanalysis. Metabolism. 2018;79:64–76. DOI: 10.1016/j.metabol.2017.11.003
97. Park H., Dawwas G.K., Liu X., Nguyen M.H. Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: a propensity-matched cohort study. J Intern Med. 2019;286:711–22. DOI: 10.1111/joim.12964
98. Yeung M.W., Wong G.L., Choi K.C., Luk A. O.-Y., Kwok R., Shu S. S.-T., et al. Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes. J Hepatol. 2017 S0168-8278(17)32334-6. DOI: 10.1016/j.jhep.2017.09.020
99. Lombardi R., Airaghi L., Targher G., Serviddio G., Maffi G., Mantovani A., et al. Liver fibrosis by FibroScan® independently of established cardiovascular risk parameters associates with macrovascular and microvascular complications in patients with type 2 diabetes. Liver Int. 2020;40(2):347–54. DOI: 10.1111/liv.14274
100. Chon Y.E., Kim H.J., Choi Y.B., Hwang S.G., Rim K.S., Kim M.N., et al. Decrease in waist-to-hip ratio reduced the development of chronic kidney disease in non-obese non-alcoholic fatty liver disease. Sci Rep. 2020;10(1):8996. DOI: 10.1038/s41598-020-65940-y
101. 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.
102. 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
103. Bedossa P. FLIP Pathology Consortium. 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
104. 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
105. Павлов Ч.С., Коновалова О.Н., Глушенков Д.В., Ивашкин В.Т. Сфера клинического применения неинвазивных методов оценки фиброза печени: результаты собственных исследований в многопрофильном стационаре. Клин мед. 2009; 87(11): 40-44
106. 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
107. Basaranoglu M., Neuschwander-Tetri B.A. Nonalcoholic Fatty Liver Disease: Clinical Features and Pathogenesis. Gastroenterol Hepatol. 2006;2(4):282–91.
108. Mc Cullough A.J. The epidemiology and risk factors of NASH. Hepatology. 2013;58(5):1644–54.
109. Obika M., Noguchi H. Diagnosis and evaluation of nonalcoholic fatty liver disease. Exp Diabetes Res. 2012;2012:145754. DOI: 10.1155/2012/145754
110. Younossi Z.M., Golabi P., De Avila L., Paik J.M., Srishord M., Fukui N., et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol. 2019;71(4):793–801. DOI: 10.1016/j.jhep.2019.06.021
111. Дедов И.И., Шестакова М.В., Майоров А.Ю., Викулова О.К., Галстян Г.Р., Кураева Т.Л., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом: Клинические рекомендации. Сахарный диабет. 2019; 22(1): 1–144. DOI: 10.14341/DM221S1.
112. Fujii H., Kawada N. and Japan Study Group of NAFLD. The role of insulin resistance and diabetes in Nonalcoholic Fatty Liver Disease, Int J Mol Sci. 2020;21:3863. DOI: 10.3390/ijms21113863
113. Кутишенко Н.П., Марцевич С.Ю., Лерман О.В., Балашов И.С., Невзорова В.А., Резник И.И. и др. Повышение эффективности гиполипидемической терапии у пациентов высокого сердечно-сосудистого риска с сочетанной патологией печени (результаты дополнительного анализа Исследования РАКУРС). Рациональная Фармакотерапия в Кардиологии. 2015;11(3):300–6.
114. Targher G., Day C.P., Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363:1341–50. DOI: 10.1056/NEJMra0912063
115. 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
116. 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
117. 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
118. 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
119. 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
120. Kotronen A., Joutsi-Korhonen L., Sevastianova K., Bergholm R., Hakkarainen A., Pietilainen 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
121. Tripodi A., Fracanzani A.L., Primignani M., Chantarangkul V., Clerici M., Mannucci P.M., et al. Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol. 2014;61(1):148–54. DOI: 10.1016/j.jhep.2014.03.013
122. Ikura Y. Transitions of histopathologic criteria for diagnosis of nonalcoholic fatty liver disease during the last three decades. World J Hepatol. 2014;12(6):894–900. DOI: 10.4254/wjh.v6.i12.894
123. 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
124. Bril F., Ortiz-Lopez C., Lomonaco R., Orsak B., Freckleton M., Chintapalli K., et al. Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver Internat. 2015;35(9):2139–46.
125. Ratziu V., Charlotte F., Heurtier A., Gombert S., Giral P., Bruckert E., et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128(7):1898–906. DOI: 10.1053/j.gastro.2005.03.084
126. Brunt E.M., Kleiner D.E., Wilson L.A., Belt P., Neuschwander-Tetri B.A., Network NCR. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011; 53:810–820. DOI: 10.1002/hep.24127
127. 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
128. 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
129. Fedchuk L., Nascimbeni F., Pais R., Charlotte F., Housset C., Ratziu V., et al. Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2014;40(10):1209–22. DOI: 10.1111/apt.12963
130. Gu J., Liu S., Du S., Zhang Q., Xiao J., Dong Q., et al. Diagnostic value of MRIPDFF 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
131. 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
132. 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;16:837–61. DOI: 10.1016/j.cgh.2017.08.024
133. 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. Hepаtology. 2017;66(5):1486–501. DOI: 10.1002/hep.29302
134. Staufer K., Halilbasic E., Spindelboeck W., Eilenberg M., Prager G., Stadlbauer V., et al. Evaluation and comparison of six noninvasive tests for prediction of significant or advanced fibrosis in nonalcoholic fatty liver disease. United European Gastroenterol J. 2019;7(8):1113–23. DOI: 10.1177/2050640619865133
135. Papatheodoridi M., Hiriart .JB., 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
136. Jiang W., Huang S., Teng H., Wang P., Wu M., Zhou X., et al. Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis, BMJ Open. 2018;8(8):e021787. DOI: 10.1136/bmjopen-2018-021787
137. 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. DOI: 10.1053/j.gastro.2015.04.005
138. 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.
139. 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
140. 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
141. 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
142. 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
143. 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
144. 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
145. 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
146. 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
147. 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
148. Kontogianni M.D., Tileli N., Margariti A., Georgoulis M., Deutsch M., Tiniakos D., et al. Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clin Nutr. 2014;33(4):678–83. DOI: 10.1016/j.clnu.2013.08.014
149. Saeed N., Nadeau B., Shannon C., Tincopa M. Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review. Nutrients. 2019;11(12):3064. DOI: 10.3390/nu11123064
150. Moosavian S.P., Arab A., Paknahad Z. The effect of a Mediterranean diet on metabolic parameters in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials. Clin Nutr ESPEN. 2020;35:40–6. DOI: 10.1016/j.clnesp.2019.10.008
151. Tendler D., Lin S., Yancy W.S. Jr, Mavropousol J., Sylvestre P., Rockey D.C., et al. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci. 2007;52(2):589–93. DOI: 10.1007/s10620-006-9433-5
152. Wong V.W., Wong G.L., Chan R.S., Shu S.S.-T., Cheung B. H.-K., 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
153. 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
154. Xia Y., Zhang S., Zhang Q., Liu L, Meng G., Wu H., et al. Insoluble dietary fibre intake is associated with lower prevalence of newly-diagnosed non-alcoholic fatty liver disease in Chinese men: a large population-based cross-sectional study. Nutr Metab (Lond). 2020;17:4. DOI: 10.1186/s12986-019-0420-1
155. Zhao L., Zhang F., Ding X., Wu G., Lam Y.Y., Wang X., et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359(6380):1151–6. DOI: 10.1126/science.aao5774
156. Kenneally S., Sier J.H., Moore J.B. Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ Open Gastroenterol. 2017;4(1):e000139. DOI: 10.1136/bmjgast-2017-000139
157. Parry S.A., Hodson L. Managing NAFLD in Type 2 Diabetes: The Effect of Lifestyle Interventions, a Narrative Review. Adv Ther. 2020;37(4):1381–406. DOI: 10.1007/s12325-020-01281-6
158. 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
159. Scragg J., Hallsworth K., Taylor G., Cassidy S., Haigh L., 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:e000678. DOI: 10.1136/bmjgast-2021-000678
160. 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
161. Lizardi-Cervera J., Aguilar-Zapata D. Nonalcoholic fatty liver disease and its association with cardiovascular disease. Annals of Hepatology. 2009;8(1):S40–S43.
162. 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
163. Polyzos S.A., Kang E.S., Boutari C., Rhee E.-J., Mantzoros C.S. Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis. Metabolism. 2020;111S:154203. DOI: 10.1016/j.metabol.2020.154203
164. 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
165. 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
166. 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.e743. DOI: 10.1016/j.cgh.2018.05.057
167. Anstee Q.M., Reeves H.L., Kotsiliti E., Govaere O., Heikenwalder M. From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol. 2019;16(7):411–28.30. DOI: 10.1038/s41575-019-0145-7
168. Liu H., Xu H.W., Zhang Y.Z., Huang Y., Han G.-Q., Liang T.-J., et al. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice. World J Gastroenterol. 2015;21(36):10367-74. DOI:10.3748/wjg.v21.i36.10367
169. Zhang H., Xu H., Zhang C., Tang Q., Bi F. Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis. Cell Death Discov. 2021;7:207. DOI: 10.1038/s41420-021-00589-8
170. Alberts D.S., Martínez M.E., Hess L.M., Einspahr J.G., Green S.B., Bhattacharyya A.K., et al. Phoenix and Tucson Gastroenterologist Networks. Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. J Natl Cancer Inst. 2005;97(11):846–53. DOI: 10.1093/jnci/dji144
171. Simental-Mendía L.E., Simental-Mendía M., Sánchez-García A., Banach M., Serban M.-C., Cicero A.F.G., et al. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Lipids Health Dis. 2019;18(1):88. DOI: 10.1186/s12944-019-1041-4
172. Nadinskaia M., Maevskaya M., Ivashkin V., Kodzoeva Kh., 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
173. Маевская М.В., Надинская М.Ю., Луньков В.Д., Пирогова И.Ю., Чесноков Е.В., Кодзоева Х.Б. и др. Влияние урсодезоксихолевой кислоты на воспаление, стеатоз и фиброз печени и факторы атерогенеза у больных неалкогольной жировой болезнью печени: результаты исследования УСПЕХ. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2019;29(6):22–9. DOI: 10.22416/1382-4376-2019-29-6-22-29
174. 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
175. 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.
176. 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
177. 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
178. Abner E.L., Schmitt FA, Mendiondo MS, Marcum J.L., Kryscio R.J. Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci. 2011;4(2):158–70. DOI: 10.2174/1874609811104020158
179. 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 non-alcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4(12):1537–43. DOI: 10.1016/j.cgh.2006.09.025
180. 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 non-alcoholic steatohepatitis. Liver Int. 2009;29(8):1184–8. DOI: 10.1111/j.1478-3231.2009.02037.x
181. 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
182. Manzillo G., Piccinino F., Surrenti C., Frezza M., Giudici G.A., et al. Multicentre Double-Blind Placebo-Controlled Study of Intravenous and Oral S-Adenosyl-L-Methionine (SAMe) in Cholestatic Patients with Liver Disease. Drug Invest. 1994;24:90–100. DOI: 10.1007/BF03258369
183. Shankar R., Virukalpattigopalratham 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. Journal of Clinical and Experimental Hepatology. 2014;4(S2):s30–8.
184. 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, placebocontrolled phase 2 study. Lancet. 2016;387(10019):679–90. DOI: 10.1016/S0140-6736(15)00803-X
185. Newsome P.N., Buchholtz K., Cusi K., Linder M., Okanoue T., Ratziu V., et al. NN9931-4296 Investigators. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021;384(12):1113–24. DOI: 10.1056/NEJMoa2028395
186. 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
187. Musso G., Cassader M., Paschetta E., Gambino R. Thiazolidinediones and Advanced Liver Fibrosis in Nonalcoholic Steatohepatitis: A Meta-analysis. JAMA In tern Med. 2017;177(5):633–40. DOI: 10.1001/jamainternmed.2016.9607
188. 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.
189. 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
190. 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
191. Li Y., Liu L., Wang B., Wang J., Chen D. Metformin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Biomed Rep. 2013;1:57–64. DOI: 10.3892/br.2012.18
192. Musso G., Gambino R., Cassader M., Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholicfatty liver disease. Hepatology. 2010;52:79–104. DOI: 10.1002/hep.23623
193. 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
194. Haufe S., Engeil S., Kast P., Bohnke 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
195. 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
196. Houmard J.A., Tanner C.J., Slentz C.A., Duscha B.D., McCartney J.S., Kraus W.E. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol. 2004;96(1):101–6. DOI: 10.1152/japplphysiol.00707.2003
197. Kopp C.W., Kopp H.P., Steiner S., Kriwanek S., Krzyzanowska K., Bartok A., et al. Weight loss reduces tissue factor in morbidly obese patients. Obes Res. 2003;11(8):950–6. DOI: 10.1038/oby.2003.131.
198. Sanyal A.J., Friedman S.L., McCullough A.J., Dimick-Santos L.; American Association for the Study of Liver Diseases; United States Food and Drug Administration. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology. 2015;61(4):1392–405. DOI: 10.1002/hep.27678
199. 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
200. 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; quiz e15–6. DOI: 10.1053/j.gastro.2015.04.014
201. 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
202. Dongiovanni P., Petta S., Mannisto V., Mancina R.M., Pipitone R., Karja V., et al. Statin use and nonalcoholic steatohepatitis in at risk individuals. J Hepatol 2015;63(3):705–12. DOI: 10.1016/j.jhep.2015.05.006
203. Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., et al. ESC Scientific Document Group. 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
204. Simon T.G., Duberg A.S., Aleman S., Hagstrom H., Nguyen L.H., Khalili H., et al. Lipophilic statins and risk for hepatocellular carcinoma and death in patients with chronic viral hepatitis: results from a Nationwide Swedish Population. Ann Intern Med. 2019;171(5):318–27. DOI: 10.7326/M18-2753
205. 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
206. Марцевич С.Ю., Кутишенко Н.П., Дроздова Л.Ю., Лерман О.В., Невзорова В.А., Резник И.И. и др. Исследование РАКУРС: повышение эффективности и безопасности терапии статинами у больных с заболеваниями печени, желчного пузыря и/или желчевыводящих путей с помощью урсодезоксихолевой кислоты. Терапевтический архив. 2014;86(12):48–52. DOI: 10.17116 /terarkh2014861248-52
207. Cabezas G.R. Efecto del ácido ursodesoxicólico combinado con estatinas para el tratamiento de la hipercolesterolemia: ensayo clínico prospectivo [Effect of ursodeoxycholic acid combined with statins in hypercholesterolemia treatment: a prospective clinical trial]. Rev Clin Esp. 2004 Dec;204(12):632–5. Spanish. DOI: 10.1016/s0014-2565(04)71566-0
208. 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
209. 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
210. 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
211. 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
212. Shimano H., Sato R. SREBP-regulated lipid metabolism: convergent physiology — divergent pathophysiology. Nat Rev Endocrinol. 2017;13:710–30. DOI: 10.1038/nrendo.2017.91
213. Marcuccilli M., Chonchol M. NAFLD and Chronic Kidney Disease. Int J Mol Sci. 2016;17(4):562. DOI: 10.3390/ijms17040562
214. Yang J.D., Hainaut P., Gores G.J., Amadou A., Plymoth A., Roberts L.R. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16:589–604. DOI: 10.1038/s41575-019-0186-y
215. Piscaglia F., Svegliati-Baroni G., Barchetti A., Pecorelli A., Marinelli S., Tiribelli C., et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study. Hepatology. 2016;63(3):827–38. DOI: 10.1002/hep.28368.
216. Stine J.G., Wentworth B.J., Zimmet A., Rinella M.E., Loomba R., Caldwell S.H., et al. Systematic review with meta-analysis: risk of hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis compared to other liver diseases. Aliment Pharmacol Ther. 2018;48(7):696–703. DOI: 10.1111/apt.14937
217. Barchetta I., Angelico F., Del Ben M., Baroni M.G., Pozzilli P., Morini S., et al. Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med. 2011;9:85. DOI: 10.1186/1741-7015-9-85
218. El-Sayed M.S., El-Sayed A., Ahmadizad S. Exercise and training effects on blood haemostasis in health and disease: an update. Sports Med. 2004;34(3):181–200. DOI: 10.2165/00007256-200434030-00004
219. Womack C.J., Nagelkirk P.R., Coughlin A.M. Exercise-induced changes in coagulation and fibrinolysis in healthy populations and patients with cardiovascular disease. Sports Med. 2003;33(11):795–807. DOI: 10.2165/00007256-200333110-00002
220. Van Stralen K.J., Le Cessie S., Rosendaal F.R., Doggen C.J. Regular sports activities decrease the risk of venous thrombosis. J Thromb Haemost. 2007;5(11):2186–92. DOI: 10.1111/j.1538-7836.2007.02732.x
221. Huh J.H., Ahn S.V., Koh S.B., Choi E., Kim J.Y., Sung K.-C., et al. A Prospective Study of fatty liver index and incident hypertension: the KoGES-ARIRANG Study. PLoS One. 2015;10(11):e0143560. DOI: 10.1371/journal.pone.0143560
222. Lau K., Lorbeer R., Haring R., Schmidt C.O., Wallaschofski H., Nauck M., et al. The association between fatty liver disease and blood pressure in a population-based prospective longitudinal study. J Hypertens. 2010;28(9):1829-35. DOI:10.1097/HJH.0b013e32833c211b
223. Ryoo J.H., Ham W.T., Choi J.M., Kang M.A., An S.H., Lee J.-K., et al. Clinical significance of non-alcoholic fatty liver disease as a risk factor for prehypertension. J Korean Med Sci. 2014;29(7):973–9. DOI: 10.3346/jkms.2014.29.7.973
224. Ryoo J.H., Suh Y.J., Shin H.C., Cho Y.K., Choi J.M., Park S.K. Clinical association between non-alcoholic fatty liver disease and the development of hypertension. J Gastroenterol Hepatol. 2014;29(11):1926–31. DOI: 10.1111/jgh.12643
225. Sung K.C., Wild S.H., Byrne C.D. Development of new fatty liver, or resolution of existing fatty liver, over five years of follow-up, and risk of incident hypertension. J Hepatol. 2014;60:1040–45. DOI: 10.1016/j.jhep.2014.01.009
226. Kupchak B.R., Creighton B.C., Aristizabal J.C., Dunn-Lewis C., Volk B.M., Ballard K.D., et al. Beneficial effects of habitual resistance exercise training on coagulation and fibrinolytic responses. Thromb Res. 2013;131(6):e227–34. DOI: 10.1016/j.thromres.2013.02.014
227. 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; quiz e61. DOI: 10.1016/j.cgh.2013.11.031
228. Boerlage T.C.C., Haal S., Maurits de Brauw L., Acherman Y.I.Z., Bruin S., van de Laar A.W.J.M., et al.Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial). BMC Gastroenterol. 2017;17(1):164. DOI: 10.1186/s12876-017-0674-x
229. Geh D., Anstee Q.M., Reeves H.L. NAFLD-Associated HCC: Progress and Opportunities. J Hepatocell Carcinoma. 2021;8:223–39. DOI: 10.2147/JHC.S272213
230. Singal A., Volk M. L., Waljee A., Salgia R., Higgins P., Rogers M.A.M., 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
Рецензия
Для цитирования:
Ивашкин В.Т., Маевская М.В., Жаркова М.С., Котовская Ю.В., Ткачева О.Н., Трошина Е.А., Шестакова М.В., Маев И.В., Бредер В.В., Гейвандова Н.И., Дощицин В.Л., Дудинская Е.Н., Ершова Е.В., Кодзоева Х.Б., Комшилова К.А., Корочанская Н.В., Майоров А.Ю., Мишина Е.Е., Надинская М.Ю., Никитин И.Г., Погосова Н.В., Тарзиманова А.И., Шамхалова М.Ш. Клинические рекомендации Российского общества по изучению печени, Российской гастроэнтерологической ассоциации, Российской ассоциации эндокринологов, Российской ассоциации геронтологов и гериатров и Национального общества профилактической кардиологии по диагностике и лечению неалкогольной жировой болезни печени. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2022;32(4):104-140. https://doi.org/10.22416/1382-4376-2022-32-4-104-140
For citation:
Ivashkin V.T., Maevskaya M.V., Zharkova M.S., Kotovskaya Yu.V., Tkacheva O.N., Troshina E.A., Shestakova M.V., Maev I.V., Breder V.V., Gheivandova N.I., Doshchitsin V.L., Dudinskaya E.N., Ershova E.V., Kodzoeva Kh.B., Komshilova K.A., Korochanskaya N.V., Mayorov A.Yu., Mishina E.E., Nadinskaya M.Yu., Nikitin I.G., Pogosova N.V., Tarzimanova A.I., Shamkhalova M.Sh. Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(4):104-140. https://doi.org/10.22416/1382-4376-2022-32-4-104-140

Контент доступен под лицензией Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.