endofocusFOCUS ЭндокринологияFOCUS. Endocrinology2713-01772713-0185ООО "Издательство "Перо"10.62751/2713-0177-2025-6-2-09endofocus-154Research ArticleОБЗОР ЛИТЕРАТУРЫLITERATURE REVIEWНеалкогольная жировая болезнь печени как звено кардиометаболического континуума: фокус на гипертриглицеридемиюNon-alcoholic fatty liver disease as a link in the cardiometabolic continuum: Focus on hypertriglyceridemiahttps://orcid.org/0000-0001-6385-540XДемидоваТ. Ю.DemidovaT. Yu.

Демидова Татьяна Юльевна – д.м.н., профессор, заведующая кафедрой эндокринологии ИКМ

г. Москва

Tatiana Yu. Demidova – D. Sci. (Med.), Professor of the Department of endocrinology, Institute of Clinical Medicine

Moscow

t.y.demidova@gmail.comhttps://orcid.org/0009-0004-5022-5790БагиловаА. Р.BagilovaA. R.

Багилова Амина Расуловна – клинический ординатор кафедры эндокринологии ИКМ

г. Москва

Amina R. Bagilova – clinical resident of the Department of endocrinology, Institute of Clinical Medicine

Moscow

amina.190199@mail.ruhttps://orcid.org/0000-0001-5512-6899УшановаФ. О.UshanovaF. O.

Ушанова Фатима Омариевна – к.м.н., доцент кафедры эндокринологии ИКМ

г. Москва

Fatima O. Ushanova – C. Sci. (Med.), Associate Professor of the Department of endocrinology, Institute of Clinical Medicine

Moscow

fati_2526@mail.ruФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииPirogov Russian National Research Medical University20252506202562Кардиоэндокринология68–75Copyright © Демидова Т.Ю., Багилова А.Р., Ушанова Ф.О., 20252025Демидова Т.Ю., Багилова А.Р., Ушанова Ф.О.Demidova T.Y., Bagilova A.R., Ushanova F.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://endofocus.elpub.ru/jour/article/view/154

Неалкогольная жировая болезнь печени (НАЖБП) – хроническое заболевание метаболического генеза у лиц с отсутствием экзогенных факторов токсического поражения печени, обусловленное накоплением липидов в составляющих печеночную дольку клеточных элементах. НАЖБП представляет собой стремительно растущую глобальную проблему здравоохранения, ассоциированную с увеличением заболеваемости и смертности. В последние годы подчеркивается тесная связь НАЖБП и кардиометаболических заболеваний, что связано с общим патогенетическими механизмами их развития. Снижение массы тела и изменение образа жизни являются основой лечения НАЖБП, но в большинстве случаев имеется потребность во внедрении фармакологических стратегий терапии. В данном обзоре представлены актуальные данные об эпидемиологии, патофизиологических аспектах развития и возможностях терапии НАЖБП, рассмотрена роль гипертриглицеридемии в развитии НАЖБП и потенциале комплексной гиполипидемической терапии в улучшении течения печеночной дисфункции.

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic disease in individuals with no exogenous factors of toxic liver damage caused by the accumulation of lipids in the cellular elements that make up the liver lobule. NAFLD is a rapidly growing global health problem associated with increased morbidity and mortality. In recent years, the close relationship between NAFLD and cardiometabolic diseases has been emphasized, which is related to the common pathogenetic mechanisms of their development. Weight loss and lifestyle changes are the mainstay of treatment, but in most cases there is a need to introduce pharmacological therapy strategies. This review presents current data on epidemiology, pathophysiological aspects of the development and treatment of NAFLD, examines the relationship of hypertriglyceridemia in the development of NAFLD and the possibility of complex lipid-lowering therapy in improving the course of liver dysfunction.

неалкогольная жировая болезнь печенисахарный диабетожирениеметаболический синдроминсулинорезистентностьгипертриглицеридемияомега-3-полиненасыщенные жирные кислотыnon-alcoholic fatty liver diseasediabetes mellitusobesitymetabolic syndromeinsulin resistancehypertriglyceridemiaomega-3 polyunsaturated fatty acidsReferencesGBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020; 5(3): 245–66. doi: 10.1016/S2468-1253(19)30349-8.GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020; 5(3): 245–66. doi: 10.1016/S2468-1253(19)30349-8.Ciardullo S, Pizzi M, Pizzi P et al. Prevalence of elevated liver stiffness among potential candidates for bariatric surgery in the United States. Obes Surg. 2022; 32(3): 712–19. doi: 10.1007/s11695-021-05885-x.Ciardullo S, Pizzi M, Pizzi P et al. Prevalence of elevated liver stiffness among potential candidates for bariatric surgery in the United States. Obes Surg. 2022; 32(3): 712–19. doi: 10.1007/s11695-021-05885-x.Евстифеева С.Е., Шальнова С.А., Куценко В.А. с соавт. Распространенность неалкогольной жировой болезни печени среди населения трудоспособного возраста: ассоциации с социально-демографическими показателями и поведенческими факторами риска (данные ЭССЕ-РФ-2). Кардиоваскулярная терапия и профилактика. 2022; 21(9): 3356. doi: 10.15829/1728-8800-2022-33564.Евстифеева С.Е., Шальнова С.А., Куценко В.А. с соавт. Распространенность неалкогольной жировой болезни печени среди населения трудоспособного возраста: ассоциации с социально-демографическими показателями и поведенческими факторами риска (данные ЭССЕ-РФ-2). Кардиоваскулярная терапия и профилактика. 2022; 21(9): 3356. doi: 10.15829/1728-8800-2022-33564.Lallukka S, Yki-Jarvinen H. Non-alcoholic fatty liver disease and risk of type 2 diabetes. Best Pract Res Clin Endocrinol Metab. 2016; 30(3): 385–95. doi: 10.1016/j.beem.2016.06.006.Lallukka S, Yki-Jarvinen H. Non-alcoholic fatty liver disease and risk of type 2 diabetes. Best Pract Res Clin Endocrinol Metab. 2016; 30(3): 385–95. doi: 10.1016/j.beem.2016.06.006.Baharvand-Ahmadi B, Sharifi K, Namdari M. Prevalence of non-alcoholic fatty liver disease in patients with coronary artery disease. ARYA Atheroscler. 2016; 12(4): 201–5.Baharvand-Ahmadi B, Sharifi K, Namdari M. Prevalence of non-alcoholic fatty liver disease in patients with coronary artery disease. ARYA Atheroscler. 2016; 12(4): 201–5.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.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.Younossi ZM, Koenig AB, Abdelatif D et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64(1): 73–84. doi: 10.1002/hep.28431.Younossi ZM, Koenig AB, Abdelatif D et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64(1): 73–84. doi: 10.1002/hep.28431.Martin A, Lang S, Goeser T et al. Management of dyslipidemia in patients with non-alcoholic fatty liver disease. Curr Atheroscler Rep. 2022; 24(7): 533–46. doi: 10.1007/s11883-022-01028-4.Martin A, Lang S, Goeser T et al. Management of dyslipidemia in patients with non-alcoholic fatty liver disease. Curr Atheroscler Rep. 2022; 24(7): 533–46. doi: 10.1007/s11883-022-01028-4.Eslam M, Newsome PN, Sarin SK et al. A new definition for metabolic dysfunctionassociated fatty liver disease: An international expert consensus statement. J Hepatol. 2020; 73(1): 202–9. doi: 10.1016/j.jhep.2020.03.039.Eslam M, Newsome PN, Sarin SK et al. A new definition for metabolic dysfunctionassociated fatty liver disease: An international expert consensus statement. J Hepatol. 2020; 73(1): 202–9. doi: 10.1016/j.jhep.2020.03.039.Rinella ME, Lazarus JV, Ratziu V et al.; NAFLD Nomenclature consensus group. A Multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023; 79(6): 1542–56. doi: 10.1016/j.jhep.2023.06.003.Rinella ME, Lazarus JV, Ratziu V et al.; NAFLD Nomenclature consensus group. A Multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023; 79(6): 1542–56. doi: 10.1016/j.jhep.2023.06.003.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 on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024; 81(3): 492–542. doi: 10.1016/j.jhep.2024.04.031.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 on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024; 81(3): 492–542. doi: 10.1016/j.jhep.2024.04.031.Gagnon E, Gobeil E, Bourgault J, Arsenault B. Abstract 15687: Triglyceride levels and non-alcoholic fatty liver disease: A multivariable Mendelian randomization study. Circulation. 2022; 146 (Suppl_1). doi: 10.1161/circ.146.suppl_1.15687.Gagnon E, Gobeil E, Bourgault J, Arsenault B. Abstract 15687: Triglyceride levels and non-alcoholic fatty liver disease: A multivariable Mendelian randomization study. Circulation. 2022; 146 (Suppl_1). doi: 10.1161/circ.146.suppl_1.15687.Boren J, Chapman MJ, Krauss RM et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2020; 41(24): 2313–30. doi: 10.1093/eurheartj/ehz962.Boren J, Chapman MJ, Krauss RM et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2020; 41(24): 2313–30. doi: 10.1093/eurheartj/ehz962.Musso G, Cassader M, Paschetta E, Gambino R. Bioactive lipid species and metabolic pathways in progression and resolution of nonalcoholic steatohepatitis. Gastroenterology. 2018; 155(2): 282–302.e8. doi: 10.1053/j.gastro.2018.06.031.Musso G, Cassader M, Paschetta E, Gambino R. Bioactive lipid species and metabolic pathways in progression and resolution of nonalcoholic steatohepatitis. Gastroenterology. 2018; 155(2): 282–302.e8. doi: 10.1053/j.gastro.2018.06.031.Semova I, Biddinger SB. Triglycerides in nonalcoholic fatty liver disease: Guilty until proven innocent. Trends Pharmacol Sci. 2021; 42(3): 183–90. doi: 10.1016/j.tips.2020.12.001.Semova I, Biddinger SB. Triglycerides in nonalcoholic fatty liver disease: Guilty until proven innocent. Trends Pharmacol Sci. 2021; 42(3): 183–90. doi: 10.1016/j.tips.2020.12.001.Xiao G, Zhu S, Xiao X et al. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology. 2017; 66(5): 1486–501. doi: 10.1002/hep.29302.Xiao G, Zhu S, Xiao X et al. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology. 2017; 66(5): 1486–501. doi: 10.1002/hep.29302.Kanwal F, Shubrook JH, Adams LA et al. Clinical care pathway for the risk stratification and management of patients with nonalcoholic fatty liver disease. Gastroenterology 2021; 161(5): 1657–69. doi: 10.1053/j.gastro.2021.07.049.Kanwal F, Shubrook JH, Adams LA et al. Clinical care pathway for the risk stratification and management of patients with nonalcoholic fatty liver disease. Gastroenterology 2021; 161(5): 1657–69. doi: 10.1053/j.gastro.2021.07.049.Клинические рекомендации. Неалкогольная жировая болезнь печени. Российская ассоциация эндокринологов, Российская гастроэнтерологическая ассоциация, Общероссийская общественная организация «Российское научное медицинское общество терапевтов», общероссийская общественная организация «Российская ассоциация геронтологов и гериатров», Российское общество по изучению печени, Российское общество профилактики неинфекционных заболеваний, Национальное общество профилактической кардиологии. Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 748_2. Доступ: https://cr.minzdrav.gov.ru/preview-cr/748_2 (дата обращения – 02.04.2025).Клинические рекомендации. Неалкогольная жировая болезнь печени. Российская ассоциация эндокринологов, Российская гастроэнтерологическая ассоциация, Общероссийская общественная организация «Российское научное медицинское общество терапевтов», общероссийская общественная организация «Российская ассоциация геронтологов и гериатров», Российское общество по изучению печени, Российское общество профилактики неинфекционных заболеваний, Национальное общество профилактической кардиологии. Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 748_2. Доступ: https://cr.minzdrav.gov.ru/preview-cr/748_2 (дата обращения – 02.04.2025).Ayada I, van Kleef LA, Zhang H et al. Dissecting the multifaceted impact of statin use on fatty liver disease: A multidimensional study. EBioMedicine. 2023; 87: 104392. doi: 10.1016/j.ebiom.2022.104392.Ayada I, van Kleef LA, Zhang H et al. Dissecting the multifaceted impact of statin use on fatty liver disease: A multidimensional study. EBioMedicine. 2023; 87: 104392. doi: 10.1016/j.ebiom.2022.104392.Choi JH, Kim SK, Lim DL, Song KH. 8697 effects of fibrate combination therapy on the prevention and progression of non-alcoholic fatty liver disease in patients with dyslipidemia undergoing statin treatment: A retrospective cohort study using Dada from the Korean National Health Insurance Service. J Endocr Soc. 2024; 8(Suppl_1): bvae163.577. doi: 10.1210/jendso/bvae163.577.Choi JH, Kim SK, Lim DL, Song KH. 8697 effects of fibrate combination therapy on the prevention and progression of non-alcoholic fatty liver disease in patients with dyslipidemia undergoing statin treatment: A retrospective cohort study using Dada from the Korean National Health Insurance Service. J Endocr Soc. 2024; 8(Suppl_1): bvae163.577. doi: 10.1210/jendso/bvae163.577.Younis IR, Weber EJ, Nelson C et al. Pharmacokinetics and safety of fenofibrate in participants with mild hepatic impairment or with advanced fibrosis due to metabolic-associated fatty liver disease. J Clin Pharmacol. 2025. Online ahead of print. doi: 10.1002/jcph.70005.Younis IR, Weber EJ, Nelson C et al. Pharmacokinetics and safety of fenofibrate in participants with mild hepatic impairment or with advanced fibrosis due to metabolic-associated fatty liver disease. J Clin Pharmacol. 2025. Online ahead of print. doi: 10.1002/jcph.70005.Francque SM, Bedossa P, Ratziu V et al.; NATIVE Study Group. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH. N Engl J Med. 2021; 385(17): 1547–58. doi: 10.1056/NEJMoa2036205.Francque SM, Bedossa P, Ratziu V et al.; NATIVE Study Group. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH. N Engl J Med. 2021; 385(17): 1547–58. doi: 10.1056/NEJMoa2036205.Aziz T, Niraj MK, Kumar S et al. Effectiveness of omega-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Cureus. 2024; 16(8): e68002. doi: 10.7759/cureus.68002.Aziz T, Niraj MK, Kumar S et al. Effectiveness of omega-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Cureus. 2024; 16(8): e68002. doi: 10.7759/cureus.68002.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): 834–38. doi: 10.1016/j.bbrc.2020.05.128.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): 834–38. doi: 10.1016/j.bbrc.2020.05.128.Grander C, Grabherr F, Tilg H. Non-alcoholic fatty liver disease: Pathophysiological concepts and treatment options. Cardiovasc Res. 2023; 119(9): 1787–98. doi: 10.1093/cvr/cvad095.Grander C, Grabherr F, Tilg H. Non-alcoholic fatty liver disease: Pathophysiological concepts and treatment options. Cardiovasc Res. 2023; 119(9): 1787–98. doi: 10.1093/cvr/cvad095.Newsome PN, Ambery P. Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver. J Hepatol. 2023; 79(6): 1557–65. doi: 10.1016/j.jhep.2023.07.033.Newsome PN, Ambery P. Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver. J Hepatol. 2023; 79(6): 1557–65. doi: 10.1016/j.jhep.2023.07.033.Gastaldelli A, Cusi K, Fernández Landó L, Bray R, Brouwers B, Rodríguez Á. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):393-406. doi: 10.1016/S2213-8587(22)00070-5.Gastaldelli A, Cusi K, Fernández Landó L, Bray R, Brouwers B, Rodríguez Á. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):393-406. doi: 10.1016/S2213-8587(22)00070-5.Jastreboff AM, Kaplan LM, Frías JP et al.; Retatrutide Phase 2 Obesity Trial Investigators. Triple-hormone-receptor agonist retatrutide for obesity – A phase 2 trial. N Engl J Med. 2023; 389(6): 514–26. doi: 10.1056/NEJMoa2301972.Jastreboff AM, Kaplan LM, Frías JP et al.; Retatrutide Phase 2 Obesity Trial Investigators. Triple-hormone-receptor agonist retatrutide for obesity – A phase 2 trial. N Engl J Med. 2023; 389(6): 514–26. doi: 10.1056/NEJMoa2301972.Kuchay MS, Krishan S, Mishra SK et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: A randomized controlled trial (E-LIFT trial). Diabetes Care. 2018; 41(8): 1801–8. doi: 10.2337/dc18-0165.Kuchay MS, Krishan S, Mishra SK et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: A randomized controlled trial (E-LIFT trial). Diabetes Care. 2018; 41(8): 1801–8. doi: 10.2337/dc18-0165.Cusi K, Orsak B, Bril F 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.Cusi K, Orsak B, Bril F 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.

The authors declare that there are no conflicts of interest present.