Неалкогольная жировая болезнь печени (НАЖБП) – основная причина заболеваемости и смертности, связанных с болезнями печени. Смертность больных НАЖБП обусловлена в основном смертностью от сердечно-сосудистых заболеваний, а не прогрессированием заболевания печени с развитием печеночно-клеточной недостаточности, осложнений портальной гипертензии и гепатоцеллюлярного рака. Большинство исследований указывает на то, что НАЖБП связана с увеличением сердечно-сосудистых заболеваний, а риск их развития увеличивается по мере прогрессирования заболевания печени.
Non-alcoholic fatty liver disease (NAFLD) is the main cause of morbidity and mortality associated with liver disease. The mortality of patients with NAFLD is due mainly to mortality from cardiovascular diseases, and not to the progression of liver disease with the development of liver failure, complications of portal hypertension and hepatocellular carcinoma. Most studies indicate that NAFLD is associated with an increase in cardiovascular disease, and the risk of their development increases with the progression of liver disease.
1. Ивашкин В.Т., Маевская М.В., Павлов Ч.С. и др. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2016; 26 (2): 24–42. / Ivashkin V.T., Maevskaia M.V., Pavlov Ch.S. i dr. Klinicheskie rekomendatsii po diagnostike i lecheniiu nealkogol'noi zhirovoi bolezni pecheni Rossiiskogo obshchestva po izucheniiu pecheni i Rossiiskoi gastroenterologicheskoi assotsiatsii. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2016; 26 (2): 24–42. [in Russian]
2. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10: 330–44.
3. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363: 1341–50.
4. Byrne CD, Targher G NAFLD: A multisystem disease. J Hepatol 2015; 62: S47–S64.
5. Francque SM, van der Graaf D, Kwanten WJ. Non-alcocholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol 2016; 65: 425–43.
6. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of noninvasive tests for liver disease severity. Ann Med 2011; 43: 617–49.
7. Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol 2012; 10: 646–50.
8. Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 2013; 57: 1357–65.
9. Wong VW, Wong GL, Yip GW et al. Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut 2011; 60: 1721–7.
10. Ekstedt M, Franzen LE, Mathiesen UL et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865–73.
11. Ekstedt M, Hagstrom H, Nasr P et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2014. http://dx.doi.org/10.1002/hep.27368
12. Zhou YJ, Li YY, Nie YQ et al. Natural course of nonalcoholic fatty liver disease in southern China: a prospective cohort study. J Dig Dis 2012; 13: 153–60.
13. Treeprasertsuk S, Leverage S, Adams LA et al. The Framingham risk score and heart disease in nonalcoholic fatty liver disease. Liver Int 2012; 32: 945–50.
14. Targher G, Bertolini L, Rodella S et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 2007; 30: 2119–21.
15. Soderberg C, Stal P, Askling J et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010; 51: 595–602.
16. Rafiq N, Bai C, Fang Y et al. Long term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol 2009; 7: 234–8.
17. Lazo M, Hernaez R, Bonekamp S et al. Nonalcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011; 343: d6891.
18. Jepsen P, Vilstrup H, Mellemkjaer L et al. Prognosis of patients with a diagnosis of fatty liver – a registry-based cohort study. Hepatogastroenterology 2003; 50: 2101–4.
19. Haring R, Wallaschofski H, Nauck M et al. Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels. Hepatology 2009; 50: 1403–11.
20. Hamaguchi M, Kojima T, Takeda N et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 2007; 13: 1579–84.
21. Adams LA, Lymp JF, Sanderson SO et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129: 113–21.
22. Ballestri S, Lonardo A, Bonapace S et al. Risk of cardiovascular, cardiac and arrhythmic complications in patients with nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20: 1724–45.
23. Oni ET, Agatston AS, Blaha MJ et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 2013; 230: 258–67.
24. Rijzewijk LJ, van der Meer RW, Smit JW et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008; 52: 1793–9.
25. Bonapace S, Perseghin G, Molon G et al. Nonalcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in patients with type 2 diabetes. Diabetes Care 2012; 35: 389–95.
26. Kim NH, Park J, Kim SH et al. Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart 2014; 100: 938–43.
27. Wannamethee SG, Whincup PH, Shaper AG et al. Gammaglutamyltransferase, hepatic enzymes, and risk of incident heart failure in older men. Arterioscler Thromb Vasc Biol 2012; 32: 830–5.
28. Sinner MF, Wang N, Fox CS et al. Relation of circulating liver transaminase concentrations to risk of new onset atrial fibrillation. Am J Cardiol 2013; 111: 219–24.
29. Alonso A, Misialek JR, Amiin MA et al. Circulating levels of liver enzymes and incidence of atrial fibrillation: the Atherosclerosis Risk in Communities cohort. Heart 2014; 100: 1151–6.
30. Targher G, Mantovani A, Pichiri I et al. Nonalcoholic fatty liver disease is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes. Clin Sci (Lond) 2013; 125: 301–9.
31. Targher G, Valbusa F, Bonapace S et al. Association of nonalcoholic fatty liver disease with QT interval in patients with type 2 diabetes. Nutr Metab Cardiovasc Dis 2014; 24: 663–9.
32. Targher G, Byrne C, Lonardo A et al. Nonalcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol 2016; 65: 589–600.
33. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64: 1388–402.
34. Широкова Е.Н. Неалкогольная жировая болезнь печени и кардиоваскулярный риск (обзор литературы). Фарматека. 2017; 2: 24–9. / Shirokova E.N. Nealkogol'naia zhirovaia bolezn' pecheni i kardiovaskuliarnyi risk (obzor literatury). Farmateka. 2017; 2: 24–9. [in Russian]
35. Бакулин И.Г., Сандлер Ю.Г. Гиполипидемическая терапия и печень. Рос. мед. вести. 2012; 17 (1): 43–51. / Bakulin I.G., Sandler Iu.G. Gipolipidemicheskaia terapiia i pechen'. Ros. med. vesti. 2012; 17 (1): 43–51. [in Russian]
36. Минушкин О.Н., Масловский Л.В. Лечение жировой болезни печени различной этиологии: современные рекомендации. Эффективная фармакотерапия. 2013; 41 (4): 38–46. / Minushkin O.N., Maslovskii L.V. Lechenie zhirovoi bolezni pecheni razlichnoi etiologii: sovremennye rekomendatsii. Effektivnaia farmakoterapiia. 2013; 41 (4): 38–46. [in Russian]
37. Мязин Р.Г. Неалкогольная болезнь печени: новые возможности терапии. Мед. совет. 2014; 13: 18–20. / Miazin R.G. Nealkogol'naia bolezn' pecheni: novye vozmozhnosti terapii. Med. sovet. 2014; 13: 18–20. [in Russian]
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1. Ivashkin V.T., Maevskaia M.V., Pavlov Ch.S. i dr. Klinicheskie rekomendatsii po diagnostike i lecheniiu nealkogol'noi zhirovoi bolezni pecheni Rossiiskogo obshchestva po izucheniiu pecheni i Rossiiskoi gastroenterologicheskoi assotsiatsii. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2016; 26 (2): 24–42. [in Russian]
2. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10: 330–44.
3. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363: 1341–50.
4. Byrne CD, Targher G NAFLD: A multisystem disease. J Hepatol 2015; 62: S47–S64.
5. Francque SM, van der Graaf D, Kwanten WJ. Non-alcocholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol 2016; 65: 425–43.
6. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of noninvasive tests for liver disease severity. Ann Med 2011; 43: 617–49.
7. Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol 2012; 10: 646–50.
8. Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 2013; 57: 1357–65.
9. Wong VW, Wong GL, Yip GW et al. Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut 2011; 60: 1721–7.
10. Ekstedt M, Franzen LE, Mathiesen UL et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865–73.
11. Ekstedt M, Hagstrom H, Nasr P et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2014. http://dx.doi.org/10.1002/hep.27368
12. Zhou YJ, Li YY, Nie YQ et al. Natural course of nonalcoholic fatty liver disease in southern China: a prospective cohort study. J Dig Dis 2012; 13: 153–60.
13. Treeprasertsuk S, Leverage S, Adams LA et al. The Framingham risk score and heart disease in nonalcoholic fatty liver disease. Liver Int 2012; 32: 945–50.
14. Targher G, Bertolini L, Rodella S et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 2007; 30: 2119–21.
15. Soderberg C, Stal P, Askling J et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010; 51: 595–602.
16. Rafiq N, Bai C, Fang Y et al. Long term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol 2009; 7: 234–8.
17. Lazo M, Hernaez R, Bonekamp S et al. Nonalcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011; 343: d6891.
18. Jepsen P, Vilstrup H, Mellemkjaer L et al. Prognosis of patients with a diagnosis of fatty liver – a registry-based cohort study. Hepatogastroenterology 2003; 50: 2101–4.
19. Haring R, Wallaschofski H, Nauck M et al. Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels. Hepatology 2009; 50: 1403–11.
20. Hamaguchi M, Kojima T, Takeda N et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 2007; 13: 1579–84.
21. Adams LA, Lymp JF, Sanderson SO et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129: 113–21.
22. Ballestri S, Lonardo A, Bonapace S et al. Risk of cardiovascular, cardiac and arrhythmic complications in patients with nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20: 1724–45.
23. Oni ET, Agatston AS, Blaha MJ et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 2013; 230: 258–67.
24. Rijzewijk LJ, van der Meer RW, Smit JW et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008; 52: 1793–9.
25. Bonapace S, Perseghin G, Molon G et al. Nonalcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in patients with type 2 diabetes. Diabetes Care 2012; 35: 389–95.
26. Kim NH, Park J, Kim SH et al. Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart 2014; 100: 938–43.
27. Wannamethee SG, Whincup PH, Shaper AG et al. Gammaglutamyltransferase, hepatic enzymes, and risk of incident heart failure in older men. Arterioscler Thromb Vasc Biol 2012; 32: 830–5.
28. Sinner MF, Wang N, Fox CS et al. Relation of circulating liver transaminase concentrations to risk of new onset atrial fibrillation. Am J Cardiol 2013; 111: 219–24.
29. Alonso A, Misialek JR, Amiin MA et al. Circulating levels of liver enzymes and incidence of atrial fibrillation: the Atherosclerosis Risk in Communities cohort. Heart 2014; 100: 1151–6.
30. Targher G, Mantovani A, Pichiri I et al. Nonalcoholic fatty liver disease is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes. Clin Sci (Lond) 2013; 125: 301–9.
31. Targher G, Valbusa F, Bonapace S et al. Association of nonalcoholic fatty liver disease with QT interval in patients with type 2 diabetes. Nutr Metab Cardiovasc Dis 2014; 24: 663–9.
32. Targher G, Byrne C, Lonardo A et al. Nonalcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol 2016; 65: 589–600.
33. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64: 1388–402.
34. Shirokova E.N. Nealkogol'naia zhirovaia bolezn' pecheni i kardiovaskuliarnyi risk (obzor literatury). Farmateka. 2017; 2: 24–9. [in Russian]
35. Bakulin I.G., Sandler Iu.G. Gipolipidemicheskaia terapiia i pechen'. Ros. med. vesti. 2012; 17 (1): 43–51. [in Russian]
36. Minushkin O.N., Maslovskii L.V. Lechenie zhirovoi bolezni pecheni razlichnoi etiologii: sovremennye rekomendatsii. Effektivnaia farmakoterapiia. 2013; 41 (4): 38–46. [in Russian]
37. Miazin R.G. Nealkogol'naia bolezn' pecheni: novye vozmozhnosti terapii. Med. sovet. 2014; 13: 18–20. [in Russian]
Авторы
Е.Н.Широкова*
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 1
*elshirokova@yandex.ru
________________________________________________
E.N.Shirokova*
I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 1
*elshirokova@yandex.ru