Неалкогольная жировая болезнь печени и сердечно-сосудистые риски

Котовская Ю.В. Неалкогольная жировая болезнь печени и сердечно-сосудистые риски. Consilium Medicum. 2023;25(4):253–258. DOI: 10.26442/20751753.2023.4.202275

© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.

________________________________________________

Kotovskaya YuV. Non-alcoholic fatty liver disease and cardiovascular risks: A review. Consilium Medicum. 2023;25(4):253–258. DOI: 10.26442/20751753.2023.4.202275

Читать PDF

Аннотация

Неалкогольная жировая болезнь печени (НАЖБП) – наиболее распространенное хроническое заболевание печени. НАЖБП часто ассоциируется с сопутствующими метаболическими нарушениями (ожирение, сахарный диабет 2-го типа, дислипидемия) и нередко рассматривается как печеночное проявление метаболического синдрома. Кроме печеночной заболеваемости и смертности НАЖБП тесно ассоциирована с субклиническими и явными сердечно-сосудистыми заболеваниями (ССЗ), что приводит к повышению сердечно-сосудистой заболеваемости и смертности, и чем более выражен печеночный процесс, тем выше риск. В этом обзоре описываются основные патофизиологические механизмы, связывающие НАЖБП и ССЗ, обсуждается роль НАЖБП как фактора риска ССЗ, а также немедикаментозные и медикаментозные методы лечения НАЖБП в контексте снижения сердечно-сосудистых рисков. Наличие НАЖБП позволяет рассматривать таких пациентов как кандидатов для более интенсивного терапевтического вмешательства для снижения печеночных и сердечно-сосудистых рисков. Модификация образа жизни, включая снижение массы тела, увеличение физической активности и коррекцию питания, составляет основу лечения НАЖБП. Коррекция сердечно-сосудистых факторов риска подразумевает использование статинов, антигипертензивных препаратов, предпочтительно блокаторов ренин-ангиотензиновой системы. Урсодезоксихолевая кислота обладает терапевтическим потенциалом для благоприятного воздействия на печеночный процесс и снижения сердечно-сосудистого риска.

Ключевые слова: неалкогольная жировая болезнь печени, сердечно-сосудистый риск, артериальная гипертония, сердечная недостаточность, урсодезоксихолевая кислота

________________________________________________

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. NAFLD may be associated with concomitant metabolic disorders (obesity, type 2 diabetes mellitus, dyslipidemia) and is often considered a hepatic manifestation of metabolic syndrome. In addition to hepatic morbidity and mortality, NAFLD is closely associated with asymptomatic and overt cardiovascular disease (CVD), leading to increased cardiovascular morbidity and mortality, and the more severe the hepatic disorder, the higher the risk. This review describes the main pathophysiological mechanisms linking NAFLD and CVD, discusses the role of NAFLD as a CVD risk factor, and addresses non-drug and drug therapies for NAFLD in the context of cardiovascular risk reduction. NAFLD makes patients candidates for more intensive therapeutic intervention to reduce hepatic and cardiovascular risks. Lifestyle modifications, including weight loss, increased physical activity, and nutritional adjustment, form the basis of NAFLD treatment. Correction of cardiovascular risk factors includes statins, antihypertensive agents, preferably renin-angiotensin system blockers. Ursodeoxycholic acid has therapeutic potential for beneficial effects on hepatic disorders and reducing cardiovascular risk.

Keywords: non-alcoholic fatty liver disease, cardiovascular risk, arterial hypertension, heart failure, ursodeoxycholic acid

Полный текст

Материалы доступны только для специалистов сферы здравоохранения.
Чтобы посмотреть материал полностью Авторизуйтесь или зарегистрируйтесь.

Список литературы

1. Маевская М.В., Котовская Ю.В., Ивашкин В.Т., и др. Национальный Консенсус для врачей по ведению взрослых пациентов с неалкогольной жировой болезнью печени и ее основными коморбидными состояниями. Терапевтический архив. 2022;94(2):216-53 [Maevskaya MV, Kotovskaya YuV, Ivashkin VT, et al. The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(2):216-53 (in Russian)]. DOI:10.26442/00403660.2022.02.201363
2. Younossi Z, Koenig A, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84. DOI:10.1002/hep.28431
3. Dulai P, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017;65:1557-65. DOI:10.1002/hep.29085
4. Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study. Gastroenterology. 2018;155:443-57. DOI:10.1053/j.gastro.2018.04.034
5. Janssen A, Grobbee D, Dendale P. Non-alcoholic fatty liver disease, a new and growing risk indicator for cardiovascular disease. Eur J Prev Cardiol. 2020;27:1059-63. DOI:10.1177/2047487319891783
6. Stahl E, Dhindsa D, Lee S, et al. Nonalcoholic fatty liver disease and the heart: JACC state of the art review. J Am Coll Cardiol. 2019;73:948-63. DOI:10.1016/j.jacc.2018.11.050.
7. Kasper P, Martin A, Lang S, et al. NAFLD and cardiovascular diseases: a clinical review. Clin Res Cardiol. 2021;110(7):921-37. DOI:10.1007/s00392-020-01709-7
8. Shulman G. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371:1131-41. DOI:10.1056/NEJMra1011035
9. Sánchez-García A, Sahebkar A, Simental-Mendía M, Simental-Mendía LE. 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
10. Shima KR, Ota T, Kato K, et al. Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study. BMJ Open Diabetes Research and Care. 2018;6:e000469. DOI:10.1136/bmjdrc-2017-000469
11. Després J. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126:1301-13. DOI:10.1161/CIRCULATIONAHA.111.067264
12. Packer M. Epicardial adipose tissue may mediate deleterious effects of obesity and inflammation on the myocardium. Cardiol J Am Coll. 2018;71:2360-72. DOI:10.1016/j.jacc.2018.03.509
13. Tang W, Bäckhed F, Landmesser U, Hazen S. Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73:2089-105.
14. Targher G, Byrne C, Lonardo A, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol. 2016;65:589-600.
15. Wu S, Wu F, Ding Y, et al. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: a systematic review and meta-analysis. Sci Rep. 2016;6:1-14. DOI:10.1038/srep33386
16. Hirata Y, Kurobe H, Akaike M, et al. Enhanced inflammation in epicardial fat in patients with coronary artery disease. Int Heart J. 2011;52:139-42. DOI:10.1536/ihj.52.139
17. Sinha S, Thakur R, Jha M, et al. Epicardial adipose tissue thickness and its association with the presence and severity of coronary artery disease in clinical setting: a cross-sectional observational study. J Clin Med Res. 2016;8:410-9. DOI:10.14740/jocmr2468w
18. Mahfood Haddad T, Hamdeh S, Kanmanthareddy A, Alla V. Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: a systematic review and meta-analysis. Diabetes Metab Syndr. 2017;11:S209-16. DOI:10.1016/j.dsx.2016.12.033
19. Mantovani A. Nonalcoholic fatty liver disease (NAFLD) and risk of cardiac arrhythmias: a new aspect of the liver-heart axis. J Clin Transl Hepatol. 2017;5:134-41. DOI:10.14218/JCTH.2017.00005
20. Mantovani A, Rigamonti A, Bonapace S, et al. Nonalcoholic fatty liver disease is associated with ventricular arrhythmias in patients with type 2 diabetes referred for clinically indicated 24-hour holter monitoring. Diabetes Care. 2016;39:1416-23. DOI:10.2337/dc16-0091
21. Targher G, Valbusa F, Bonapace S, et al. Non-alcoholic fatty liver disease is associated with an increased incidence of atrial fibrillation in patients with type 2 diabetes. PLoS ONE. 2013;8:e57183. DOI:10.1371/journal.pone.0057183
22. Capone F, Vettor R, Schiattarella GG. Cardiometabolic HFpEF: NASH of the Heart. Circulation. 2023;147:451-3. DOI:10.1161/CIRCULATIONAHA.122.062874
23. Mantovani A, Petracca G, Csermely A, et al. Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals. Gut. 2022:gutjnl-2022-327672. DOI:10.1136/gutjnl-2022-327672
24. Stefan N, Häring H, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019;7:313-24. DOI:10.1016/S2213-8587(18)30154-2
25. Wu P, Zhao J, Guo Y, et al. Ursodeoxycholic acid alleviates nonalcoholic fatty liver disease by inhibiting apoptosis and improving autophagy via activating AMPK. Biochem Biophys Res Commun. 2020;529(3):834-8.
26. Dufour JF, Oneta CM, Gonvers JJ, et al. Swiss Association for the Study of the Liver. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4(12):1537-43. DOI:10.1016/j.cgh.2006.09.025
27. Ratziu V, de Ledinghen V, Oberti F, et al. FRESGUN. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011;54(5):1011-9. DOI:10.1016/j.jhep.2010.08.030
28. Mappala H. The efficacy of ursodeoxycholic acid in the treatment of non-alcoholic steatohepatitis: A 15-year systematic review. Gut. 2019;68(Suppl. 1):A1-166.
29. Simental-Mendía LE, Simental-Mendía M, Sánchez-García A, 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
30. Марцевич С.Ю., Кутишенко Н.П., Дроздова Л.Ю., и др. Изучение влияния урсодезоксихолевой кислоты на эффективность и безопасность терапии статинами у больных с заболеваниями печени, желчного пузыря и/или желчевыводящих путей (исследование РАКУРС). Рациональная фармакотерапия в кардиологии. 2014;10(2):147-52 [Martsevich SYu, Kutishenko NP, Drozdova LYu, et al. Study of ursodeoxycholic acid influence on efficacy and safety of statin therapy in patients with diseases of the liver, gall bladder and/or biliary tract (the RAKURS study). Rational Pharmacotherapy in Cardiology. 2014;10(2):147-152 (in Russian)].
31. Nadinskaia M, Maevskaya M, Ivashkin V, 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
32. Пирогова И.Ю., Яковлева С.В., Неуймина Т.В., и др. Влияние препарата УрСосан на стеатоз и Фиброз печени, а также показатЕли метаболического синдРома у больных с неалкогольной жировой болезнью печени: сравнительное исследование «СФЕРА». Гастроэнтерология. Consilium Medicum. 2018;1:7-14 [Pirogova IYu, Yakovleva SV, Neujmina TV, et al. Pleiotropic effects of Ursosan in non-alcoholic fatty liver disease and metabolic syndrome. Gastroenterology (Suppl. Consilium Medicum). 2018;1:7-14 (in Russian)]. DOI:10.26442/2414-3529_2018.1.7-14

________________________________________________

1. Maevskaya MV, Kotovskaya YuV, Ivashkin VT, et al. The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(2):216-53 (in Russian). DOI:10.26442/00403660.2022.02.201363
2. Younossi Z, Koenig A, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84. DOI:10.1002/hep.28431
3. Dulai P, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017;65:1557-65. DOI:10.1002/hep.29085
4. Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study. Gastroenterology. 2018;155:443-57. DOI:10.1053/j.gastro.2018.04.034
5. Janssen A, Grobbee D, Dendale P. Non-alcoholic fatty liver disease, a new and growing risk indicator for cardiovascular disease. Eur J Prev Cardiol. 2020;27:1059-63. DOI:10.1177/2047487319891783
6. Stahl E, Dhindsa D, Lee S, et al. Nonalcoholic fatty liver disease and the heart: JACC state of the art review. J Am Coll Cardiol. 2019;73:948-63. DOI:10.1016/j.jacc.2018.11.050.
7. Kasper P, Martin A, Lang S, et al. NAFLD and cardiovascular diseases: a clinical review. Clin Res Cardiol. 2021;110(7):921-37. DOI:10.1007/s00392-020-01709-7
8. Shulman G. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371:1131-41. DOI:10.1056/NEJMra1011035
9. Sánchez-García A, Sahebkar A, Simental-Mendía M, Simental-Mendía LE. 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
10. Shima KR, Ota T, Kato K, et al. Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study. BMJ Open Diabetes Research and Care. 2018;6:e000469. DOI:10.1136/bmjdrc-2017-000469
11. Després J. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126:1301-13. DOI:10.1161/CIRCULATIONAHA.111.067264
12. Packer M. Epicardial adipose tissue may mediate deleterious effects of obesity and inflammation on the myocardium. Cardiol J Am Coll. 2018;71:2360-72. DOI:10.1016/j.jacc.2018.03.509
13. Tang W, Bäckhed F, Landmesser U, Hazen S. Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73:2089-105.
14. Targher G, Byrne C, Lonardo A, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol. 2016;65:589-600.
15. Wu S, Wu F, Ding Y, et al. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: a systematic review and meta-analysis. Sci Rep. 2016;6:1-14. DOI:10.1038/srep33386
16. Hirata Y, Kurobe H, Akaike M, et al. Enhanced inflammation in epicardial fat in patients with coronary artery disease. Int Heart J. 2011;52:139-42. DOI:10.1536/ihj.52.139
17. Sinha S, Thakur R, Jha M, et al. Epicardial adipose tissue thickness and its association with the presence and severity of coronary artery disease in clinical setting: a cross-sectional observational study. J Clin Med Res. 2016;8:410-9. DOI:10.14740/jocmr2468w
18. Mahfood Haddad T, Hamdeh S, Kanmanthareddy A, Alla V. Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: a systematic review and meta-analysis. Diabetes Metab Syndr. 2017;11:S209-16. DOI:10.1016/j.dsx.2016.12.033
19. Mantovani A. Nonalcoholic fatty liver disease (NAFLD) and risk of cardiac arrhythmias: a new aspect of the liver-heart axis. J Clin Transl Hepatol. 2017;5:134-41. DOI:10.14218/JCTH.2017.00005
20. Mantovani A, Rigamonti A, Bonapace S, et al. Nonalcoholic fatty liver disease is associated with ventricular arrhythmias in patients with type 2 diabetes referred for clinically indicated 24-hour holter monitoring. Diabetes Care. 2016;39:1416-23. DOI:10.2337/dc16-0091
21. Targher G, Valbusa F, Bonapace S, et al. Non-alcoholic fatty liver disease is associated with an increased incidence of atrial fibrillation in patients with type 2 diabetes. PLoS ONE. 2013;8:e57183. DOI:10.1371/journal.pone.0057183
22. Capone F, Vettor R, Schiattarella GG. Cardiometabolic HFpEF: NASH of the Heart. Circulation. 2023;147:451-3. DOI:10.1161/CIRCULATIONAHA.122.062874
23. Mantovani A, Petracca G, Csermely A, et al. Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals. Gut. 2022:gutjnl-2022-327672. DOI:10.1136/gutjnl-2022-327672
24. Stefan N, Häring H, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019;7:313-24. DOI:10.1016/S2213-8587(18)30154-2
25. Wu P, Zhao J, Guo Y, et al. Ursodeoxycholic acid alleviates nonalcoholic fatty liver disease by inhibiting apoptosis and improving autophagy via activating AMPK. Biochem Biophys Res Commun. 2020;529(3):834-8.
26. Dufour JF, Oneta CM, Gonvers JJ, et al. Swiss Association for the Study of the Liver. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4(12):1537-43. DOI:10.1016/j.cgh.2006.09.025
27. Ratziu V, de Ledinghen V, Oberti F, et al. FRESGUN. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011;54(5):1011-9. DOI:10.1016/j.jhep.2010.08.030
28. Mappala H. The efficacy of ursodeoxycholic acid in the treatment of non-alcoholic steatohepatitis: A 15-year systematic review. Gut. 2019;68(Suppl. 1):A1-166.
29. Simental-Mendía LE, Simental-Mendía M, Sánchez-García A, 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
30. Martsevich SYu, Kutishenko NP, Drozdova LYu, et al. Study of ursodeoxycholic acid influence on efficacy and safety of statin therapy in patients with diseases of the liver, gall bladder and/or biliary tract (the RAKURS study). Rational Pharmacotherapy in Cardiology. 2014;10(2):147-152 (in Russian).
31. Nadinskaia M, Maevskaya M, Ivashkin V, 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
32. Pirogova IYu, Yakovleva SV, Neujmina TV, et al. Pleiotropic effects of Ursosan in non-alcoholic fatty liver disease and metabolic syndrome. Gastroenterology (Suppl. Consilium Medicum). 2018;1:7-14 (in Russian). DOI:10.26442/2414-3529_2018.1.7-14

Авторы

Ю.В. Котовская*

ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*kotovskaya_yv@rgnkc.ru

________________________________________________

Yulia V. Kotovskaya*

Pirogov Russian National Research Medical University, Moscow, Russia
*kotovskaya_yv@rgnkc.ru

Назад к списку

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