Ожирение и неалкогольная жировая болезнь печени: кардиометаболические риски и их коррекция

Комшилова К.А., Мазурина Н.В., Ершова Е.В., Трошина Е.А. Ожирение и неалкогольная жировая болезнь печени: кардиометаболические риски и их коррекция. Consilium Medicum. 2021; 23 (4): 332–337.
DOI: 10.26442/20751753.2021.4.200887

________________________________________________

Komshilova KA, Mazurina NV, Ershova EV, Troshina EA. Obesity and non-alcoholic fatty liver disease: cardiometabolic risks and their correction. Consilium Medicum. 2021; 23 (4): 332–337.
DOI: 10.26442/20751753.2021.4.200887

Читать PDF

Аннотация

Неалкогольная жировая болезнь печени (НАЖБП) – распространенное хроническое заболевание печени, тесно ассоциированное с ожирением, особенно абдоминальным, и метаболическим синдромом, что значительно повышает кардиометаболический риск и отражается на заболеваемости, прогнозе и продолжительности жизни больных. НАЖБП на стадии стеатоза не повышает риск смертности в общей популяции, однако потенциально опасная стадия – неалкогольный стеатогепатит – во многих случаях остается своевременно не распознанной и в отсутствие адекватного лечения может прогрессировать и приводить к развитию цирроза, печеночной недостаточности и гепатоцеллюлярной карциномы. Вопросы лечения НАЖБП в настоящее время приобрели особую актуальность в связи с высокой распространенностью ожирения, сахарного диабета типа 2, кардиоваскулярных заболеваний и их осложнений. Терапия НАЖБП должна быть направлена в первую очередь на этиопатогенетические факторы, способствующие ее развитию и прогрессированию, а также коррекцию ассоциированных метаболических нарушений. Растущая распространенность ожирения, НАЖБП и связанных с ними факторов риска, трудности диагностики и отсутствие общепринятого алгоритма ведения таких больных еще раз подтверждают актуальность данной проблемы. В статье изложены основные механизмы патогенеза НАЖБП, ее роль при ожирении, прогноз заболевания, диагностика и лечение.

Ключевые слова: ожирение, неалкогольная жировая болезнь печени, метаболический синдром, кардиометаболические факторы риска

________________________________________________

Non-alcoholic fatty liver disease (NAFLD) is the common chronic disease, associated with obesity, especially abdominal obesity, and a metabolic syndrome, that considerably raises cardiometabolic risk and is reflected in morbidity, prognosis of the disease and life expectancy of patients. NAFLD at the stage of steatosis does not increase the risk of mortality in the general population, however, the potentially dangerous stage, non-alcoholic steatohepatitis, in many cases remains unrecognized in a timely manner and, in the absence of adequate treatment, can progress and lead to the development of cirrhosis, liver failure, and hepatocellular carcinoma. The issues of NAFLD treatment are relevant due to the high prevalence of obesity, diabetes mellitus type 2, cardiovascular diseases and their complications. NAFLD therapy should be aimed primarily at the etiopathogenetic factors that contribute to its development and progression, as well as the correction of associated metabolic disorders. The growing prevalence of obesity, NAFLD and associated risk factors, diagnostic difficulties and the lack of an algorithm for managing such patients confirm the urgency of this problem. In this article describes the basic mechanisms of pathogenesis NAFLD, its role in obesity, prognosis of the disease, diagnostics and treatment.

Keywords: obesity, non-alcoholic fatty liver disease, metabolic syndrome, cardiometabolic risk factors

Полный текст

Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.

Список литературы

1. Дедов И.И., Шестакова М.В., Мельниченко Г.А., и др. Междисциплинарные клинические рекомендации «Лечение ожирения и коморбидных заболеваний». Ожирение и метаболизм. 2021;18(1):5-99 [Dedov II, Shestakova MV, Mel’nichenko GA, et al. Mezhdistsiplinarnye klinicheskie rekomendatsii “Lechenie ozhireniia i komorbidnykh zabolevanii”. Ozhirenie i metabolizm. 2021;18(1):5-99 (in Russsian)].
2. Lazo M, Clark J. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28(4):339-50.
3. Misra V, Khashab M, Chalasani N. Nonalcoholic fatty liver disease and cardiovascular risk. Curr Gastroenterol Rep. 2009;11:50-5.
4. Stefan N, Kantartzis K, Häring HU. Causes and metabolic consequences of fatty liver. Endocr Rev. 2008;29(7):939-60.
5. Musso G, Gambino R, Cassader M. Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obes Rev. 2010;11(6):430-45.
6. Dowman J, Tomlinson J, Newsome P. Pathogenesis of non-alcoholic fatty liver disease. QJM. 2010;103(2):71-83.
7. Nafisa A, Gray SG, Cao Y, et al. Endotelial function and dysfunction: impact of metformin. Pharmacol Ther. 2018;192:150-62.
8. Ong J, Younossi Z. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11:1-16.
9. Leite N, Salles GF, Araujo AL, et al. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009;29:113-9.
10. Younossi Z, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver desease – Meta-analytic assessment of prevalence, incidence and outcomes. Hepatology. 2016;64:73-84.
11. EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO). J Hepatol. 2016;64(6):1388-402.
12. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811-26.
13. Chalasani N, Younossi Z, Lavine JE, 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;67:328-57.
14. Utzschneider K, Kahn S. The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2006;91(12):4753-61.
15. Targher G, Bertolini L, Scala L, et al. 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.
16. Diehl AM, et al. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut. 2005;54:303-6.
17. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis and the metabolic syndrome. Hepatology. 2003;37:917-23.
18. Haufe S, Engeli S, Kast P, et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology. 2011;53:1504-14.
19. Asrih M, Jornayvaz FR. Diets and nonalcoholic fatty liver disease: the good and the bad. Clin Nutr. 2014;33:186-90.
20. Houmard J, TannerCJ, Slentz CA, et al. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol. 2004;96:101-6.
21. Kopp C, Kopp HP, Steiner S, et al. Weight loss reduces tissue factor in morbidly obese patients. Obes Res. 2003;11(8):950-6.
22. 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;61:1392-405.
23. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52:79-104.
24. Vilsbøll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771.
25. Armstrong M, Gaunt P, Aithal GP, 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;387:679-90.
26. Li Y, Liu L, Wang B, et al. Metformin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Biomed Rep. 2013;1:57-64.
27. DPP Research Group. The Diabetes Prevention Program: Lifestyle modification and metformin reduce the incidence of type 2 diabetes mellitus. N Engl J Med. 2002;346:393-403.
28. Doycheva I, Loomba R. Effect of metformin on ballooning degeneration in nonalcoholic steatohepatitis (NASH): when to use metformin in nonalcoholic fatty liver disease (NAFLD). Adv Ther. 2014;31:30-43.
29. Garinis G, Fruci B, Mazza A, et al. Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study. Int J Obes (Lond). 2010;34:1255-64.
30. Nair S, Diehl AM, Wiseman M, et al. Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004;20:23-8.
31. Loomba R, Lutchman G, Kleiner DE, et al. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2009;29:172-82.
32. de Oliveira C, Stefano JT, de Siqueira ER, et al. Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis. Hepatol Res. 2008;38:159-65.
33. Shields W, Thompson KE, Grice GA, et al. The effect of metformin and standard therapy versus standard therapy alone in nondiabetic patients with insulin resistance and nonalcoholic steatohepatitis (NASH): A pilot trial. Therap Adv Gastroenterol. 2009;2:157-63.
34. Uygun A, Kadayifci A, Isiket AT, et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2004;19:537-44.
35. Haukeland J, Konopski Z, Eggesbø HB, et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009;44:853-60.
36. Sanyal A, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-85.
37. Sato K, Gosho M, Yamamoto T, et al. Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition. 2015;31:923-30.
38. Xu R, Tao A, Zhang S, et al. Association between vitamin E and non-alcoholic steatohepatitis: a meta-analysis. Int J Clin Exp Med. 2015;8:3924-34.
39. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379-88.
40. Miller E, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46.
41. Abner E, Schmitt FA, Mendiondo MS, et al. Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci. 2011;4:158-70.
42. Bower G, Toma T, Harling L, et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg. 2015;25:2280-9.

________________________________________________

1. Dedov II, Shestakova MV, Mel’nichenko GA, et al. Mezhdistsiplinarnye klinicheskie rekomendatsii “Lechenie ozhireniia i komorbidnykh zabolevanii”. Ozhirenie i metabolizm. 2021;18(1):5-99 (in Russsian)
2. Lazo M, Clark J. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28(4):339-50.
3. Misra V, Khashab M, Chalasani N. Nonalcoholic fatty liver disease and cardiovascular risk. Curr Gastroenterol Rep. 2009;11:50-5.
4. Stefan N, Kantartzis K, Häring HU. Causes and metabolic consequences of fatty liver. Endocr Rev. 2008;29(7):939-60.
5. Musso G, Gambino R, Cassader M. Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obes Rev. 2010;11(6):430-45.
6. Dowman J, Tomlinson J, Newsome P. Pathogenesis of non-alcoholic fatty liver disease. QJM. 2010;103(2):71-83.
7. Nafisa A, Gray SG, Cao Y, et al. Endotelial function and dysfunction: impact of metformin. Pharmacol Ther. 2018;192:150-62.
8. Ong J, Younossi Z. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11:1-16.
9. Leite N, Salles GF, Araujo AL, et al. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009;29:113-9.
10. Younossi Z, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver desease – Meta-analytic assessment of prevalence, incidence and outcomes. Hepatology. 2016;64:73-84.
11. EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO). J Hepatol. 2016;64(6):1388-402.
12. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811-26.
13. Chalasani N, Younossi Z, Lavine JE, 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;67:328-57.
14. Utzschneider K, Kahn S. The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2006;91(12):4753-61.
15. Targher G, Bertolini L, Scala L, et al. 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.
16. Diehl AM, et al. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut. 2005;54:303-6.
17. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis and the metabolic syndrome. Hepatology. 2003;37:917-23.
18. Haufe S, Engeli S, Kast P, et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology. 2011;53:1504-14.
19. Asrih M, Jornayvaz FR. Diets and nonalcoholic fatty liver disease: the good and the bad. Clin Nutr. 2014;33:186-90.
20. Houmard J, TannerCJ, Slentz CA, et al. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol. 2004;96:101-6.
21. Kopp C, Kopp HP, Steiner S, et al. Weight loss reduces tissue factor in morbidly obese patients. Obes Res. 2003;11(8):950-6.
22. 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;61:1392-405.
23. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52:79-104.
24. Vilsbøll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771.
25. Armstrong M, Gaunt P, Aithal GP, 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;387:679-90.
26. Li Y, Liu L, Wang B, et al. Metformin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Biomed Rep. 2013;1:57-64.
27. DPP Research Group. The Diabetes Prevention Program: Lifestyle modification and metformin reduce the incidence of type 2 diabetes mellitus. N Engl J Med. 2002;346:393-403.
28. Doycheva I, Loomba R. Effect of metformin on ballooning degeneration in nonalcoholic steatohepatitis (NASH): when to use metformin in nonalcoholic fatty liver disease (NAFLD). Adv Ther. 2014;31:30-43.
29. Garinis G, Fruci B, Mazza A, et al. Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study. Int J Obes (Lond). 2010;34:1255-64.
30. Nair S, Diehl AM, Wiseman M, et al. Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004;20:23-8.
31. Loomba R, Lutchman G, Kleiner DE, et al. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2009;29:172-82.
32. de Oliveira C, Stefano JT, de Siqueira ER, et al. Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis. Hepatol Res. 2008;38:159-65.
33. Shields W, Thompson KE, Grice GA, et al. The effect of metformin and standard therapy versus standard therapy alone in nondiabetic patients with insulin resistance and nonalcoholic steatohepatitis (NASH): A pilot trial. Therap Adv Gastroenterol. 2009;2:157-63.
34. Uygun A, Kadayifci A, Isiket AT, et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2004;19:537-44.
35. Haukeland J, Konopski Z, Eggesbø HB, et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009;44:853-60.
36. Sanyal A, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-85.
37. Sato K, Gosho M, Yamamoto T, et al. Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition. 2015;31:923-30.
38. Xu R, Tao A, Zhang S, et al. Association between vitamin E and non-alcoholic steatohepatitis: a meta-analysis. Int J Clin Exp Med. 2015;8:3924-34.
39. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379-88.
40. Miller E, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46.
41. Abner E, Schmitt FA, Mendiondo MS, et al. Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci. 2011;4:158-70.
42. Bower G, Toma T, Harling L, et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg. 2015;25:2280-9.

Авторы

К.А. Комшилова*, Н.В. Мазурина, Е.В. Ершова, Е.А. Трошина

ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
*kom-ksusha@rambler.ru

________________________________________________

Kseniya A. Komshilova*, Natalya V. Mazurina, Ekaterina V. Ershova, Ekaterina A. Troshina

Endocrinology Research Centre, Moscow, Russia
*kom-ksusha@rambler.ru

Назад к списку

Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.