Особенности метаболических нарушений у мужчин и женщин с неалкогольной жировой болезнью печени

Автор: Шаабани С.А., Пчелин И.Ю.

Статья в выпуске: 6 т.6, 2020 года.

Бесплатный доступ

В настоящее время неалкогольная жировая болезнь печени (НАЖБП) рассматривается как мультисистемное заболевание, ассоциированное с метаболическим синдромом. Половые различия прослеживаются как в распределении заболеваемости НАЖБП в популяции, так и в преобладании тех или иных метаболических нарушений у пациентов со стеатозом печени. В статье проанализированы современные научные данные об эпидемиологии и патогенезе заболевания, в том числе о роли половых гормонов в развитии стеатоза. Суммированы данные об основных метаболических нарушениях у пациентов с НАЖБП, обсуждаются потенциальные механизмы их взаимосвязи с гормональным статусом. Рассмотрены особенности взаимосвязи НАЖБП с синдромом поликистозных яичников у женщин. Результаты проведенного анализа данных литературы свидетельствуют о целесообразности разработки стратегий диагностики метаболических нарушений у пациентов с НАЖБП, а также рекомендаций по персонализированной терапии с учетом пола и гормонального статуса пациентов.

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Неалкогольная жировая болезнь печени, метаболический синдром, инсулинорезистентность, синдром поликистозных яичников, эстрогены, половые различия, гомоцистеин, лептин, мочевая кислота

Короткий адрес: https://sciup.org/14121385

IDR: 14121385

Список литературы Особенности метаболических нарушений у мужчин и женщин с неалкогольной жировой болезнью печени

Younossi ZM. Non-alcoholic fatty liver disease – A global public health perspective. J Hepatol. 2019;70(3):531-544. DOI: 10.1016/j.jhep.2018.10.033
Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):S47-S64. DOI: 10.1016/j.jhep.2014.12.012
LaBrecque DR, Abbas Z, Anania F, et al. World Gastroenterology Organisation global guidelines: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014;48(6):467-473. DOI: 10.1097/MCG.0000000000000116
Younossi ZM, Stepanova M, Afendy M, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011;9(6):524-e60. DOI: 10.1016/j.cgh.2011.03.020
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. 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
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274-285. DOI: 10.1111/j.1365-2036.2011.04724.x
Ивашкин В.Т., Драпкина О.М., Маев И.В., и др. Распространенность неалкогольной жировой болезнипечени у пациентов амбулаторно-поликлинической практики в Российской Федерации: результаты исследования DIREG 2 // Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2015. Т. 25. № 6. С. 31-41. [Ivashkin VT, Drapkina OM, Mayev IV, et al. Prevalence of non-alcoholic fatty liver disease in out-patients of the Russian Federation: DIREG 2 study results. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(6):31-41. (in Russ)]
Пальгова Л.К., Барановский А.Ю., Ушакова Т.И., и др. Эпидемиологические особенности неалкогольной жировой болезни печени в Северо-Западном регионе России (результаты открытого многоцентрового проспективного исследования DIREG 2) // Вестник Санкт-Петербургского университета. Медицина. 2017. Т. 12. № 2. С. 118-135. [Palgova LK, Baranovsky AY, Ushakova TI, et al. Epidemiological features of non-alcoholic fatty liver disease in the North-West region of Russia (Results of an open multicenter prospective study DIREG 2). Vestnik of St Petersburg University. Medicine. 2017;12(2):118-135. (in Russ)]. DOI: 10.21638/11701/spbu11.2017.201.
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 // Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016. Т. 26. № 2. С. 24-42. [Ivashkin VT, Mayevskaya MV, Pavlov CS, et al. Diagnostics and treatment of non-alcoholic fatty liver disease: clinical guidelines of the Russian Scientific Liver Society and the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;26(2):24-42. (In Russ)]. DOI: 10.22416/1382-4376-2016-26-2-24-42
Li Z, Xue J, Chen P, et al. Prevalence of nonalcoholic fatty liver disease in mainland of China: a meta-analysis of published studies. J Gastroenterol Hepatol. 2014;29(1):42-51. DOI: 10.1111/jgh.12428
van den Berg EH, Amini M, Schreuder TC, et al. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort. PLoS One. 2017;12(2):e0171502. DOI: 10.1371/journal.pone.0171502
Lazo M, Hernaez R, Eberhardt MS, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol. 2013;178(1):38-45. DOI: 10.1093/aje/kws448
Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol. 2008;49(4):608-612. DOI: 10.1016/j.jhep.2008.06.018
Papatheodoridis GV, Goulis J, Christodoulou D, et al. High prevalence of elevated liver enzymes in blood donors: associations with male gender and central adiposity. Eur J Gastroenterol Hepatol. 2007;19(4):281-287. DOI: 10.1097/MEG.0b013e328011438b
Kallwitz ER, Kumar M, Aggarwal R, et al. Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: the impact of triglycerides. Dig Dis Sci. 2008;53(5):1358-1363. DOI: 10.1007/s10620-008-0234-x
Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology. 2007;132(6):2087-2102. DOI: 10.1053/j.gastro.2007.03.052
Wang Z, Xu M, Peng J, et al. Prevalence and associated metabolic factors of fatty liver disease in the elderly. Exp Gerontol. 2013;48(8):705-709. DOI: 10.1016/j.exger.2013.05.059
Wang Z, Xu M, Hu Z, Shrestha UK. Prevalence of nonalcoholic fatty liver disease and its metabolic risk factors in women of different ages and body mass index. Menopause. 2015;22(6):667-673. DOI: 10.1097/GME.0000000000000352
Eguchi Y, Hyogo H, Ono M, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol. 2012;47(5):586-595. DOI: 10.1007/s00535-012-0533-z
Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65(8):1038-1048. DOI: 10.1016/j.metabol.2015.12.012
Маршалко Д.В., Пчелин И.Ю., Шишкин А.Н. Неалкогольная жировая болезнь печени: коморбидность, клиническое значение и методы диагностики фиброза печени // Juvenis scientia. 2018. №. 2. С. 14-17. [Marshalko DV, Pchelin IY, Shishkin AN. Nonalcoholic fatty liver disease: comorbidities, clinical significance and evaluation of liver fibrosis. Juvenis scientia. 2018;(2):14-17. (in Russ)]
Cusi K. Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis. Clin Liver Dis. 2009;13(4):545-563. DOI: 10.1016/j.cld.2009.07.009
Loomba R, Schork N, Chen CH, et al. Heritability of Hepatic Fibrosis and Steatosis Based on a Prospective Twin Study. Gastroenterology. 2015;149(7):1784-1793. DOI: 10.1053/j.gastro.2015.08.011
Eslam M, Valenti L, Romeo S. Genetics and epigenetics of NAFLD and NASH: Clinical impact. J Hepatol. 2018;68(2):268-279. DOI: 10.1016/j.jhep.2017.09.003
Dongiovanni P, Romeo S, Valenti L. Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis. Biomed Res Int. 2015;2015:460190. DOI: 10.1155/2015/460190
Yang JD, Abdelmalek MF, Pang H, et al. Gender and menopause impact severity of fibrosis among patientswith nonalcoholic steatohepatitis. Hepatology. 2014;59(4):1406-1414. DOI: 10.1002/hep.26761
Palmisano BT, Zhu L, Stafford JM. Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017;1043:227-256. DOI: 10.1007/978-3-319-70178-3_12
Lee C, Kim J, Jung Y. Potential Therapeutic Application of Estrogen in Gender Disparity of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis. Cells. 2019;8(10):1259. DOI: 10.3390/cells8101259
Hart-Unger S, Arao Y, Hamilton KJ, et al. Hormone signaling and fatty liver in females: analysis of estrogen receptor α mutant mice. Int J Obes (Lond). 2017;41(6):945-954. DOI: 10.1038/ijo.2017.50
Ohlsson C, Hellberg N, Parini P, et al. Obesity and disturbed lipoprotein profile in estrogen receptoralpha-deficient male mice (published correction appears in Biochem Biophys Res Commun. 2006 Sep 15;348(1):326. Bohlooly, M (corrected to Bohlooly-Y, M)). Biochem Biophys Res Commun. 2000;278(3):640-645. DOI: 10.1006/bbrc.2000.3827
Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man (published correction appears in N Engl J Med 1995 Jan 12;332(2):131). N Engl J Med. 1994;331(16):1056-1061. DOI: 10.1056/NEJM199410203311604
Nemoto Y, Toda K, Ono M, et al. Altered expression of fatty acid-metabolizing enzymes in aromatasedeficient mice. J Clin Invest. 2000;105(12):1819-1825. DOI: 10.1172/JCI9575
Pighon A, Gutkowska J, Jankowski M, et al. Exercise training in ovariectomized rats stimulates estrogeniclike effects on expression of genes involved in lipid accumulation and subclinical inflammation in liver. Metabolism. 2011;60(5):629-639. DOI: 10.1016/j.metabol.2010.06.012
Magkos F, Patterson BW, Mohammed BS, et al. Women produce fewer but triglyceride-richer very lowdensity lipoproteins than men. J Clin Endocrinol Metab. 2007;92(4):1311-1318. DOI: 10.1210/jc.2006-2215
Paquette A, Wang D, Jankowski M, et al. Effects of ovariectomy on PPAR alpha, SREBP-1c, and SCD-1 gene expression in the rat liver. Menopause. 2008;15(6):1169-1175. DOI: 10.1097/gme.0b013e31817b8159
Lee B, Jung EA, Yoo JJ, et al. Prevalence, incidence and risk factors of tamoxifen-related non-alcoholic fatty liver disease: A systematic review and meta-analysis. Liver Int. 2020;40(6):1344-1355. DOI: 10.1111/ liv.14434
Florio AA, Graubard BI, Yang B, et al. Oophorectomy and risk of non-alcoholic fatty liver disease and primary liver cancer in the Clinical Practice Research Datalink. Eur J Epidemiol. 2019;34(9):871-878. DOI: 10.1007/s10654-019-00526-1
McKenzie J, Fisher BM, Jaap AJ, et al. Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial. Clin Endocrinol (Oxf). 2006;65(1):40-44. DOI: 10.1111/j.1365-2265.2006.02543.x
Cole LK, Jacobs RL, Vance DE. Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology. 2010;52(4):1258-1265. DOI: 10.1002/hep.23813
Hong N, Yoon HG, Seo DH, et al. Different patterns in the risk of newly developed fatty liver and lipid changes with tamoxifen versus aromatase inhibitors in postmenopausal women with early breast cancer: A propensity score-matched cohort study. Eur J Cancer. 2017;82:103-114. DOI: 10.1016/j.ejca.2017.05.002
Yoo JJ, Lim YS, Kim MS, et al. Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer. PLoS One. 2020;15(7):e0236506. DOI: 10.1371/journal.pone.0236506
Godsland IF. Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from 1974-2000. Fertil Steril. 2001;75(5):898-915. DOI: 10.1016/s0015-0282(01)01699-5
Wolfe BM, Plunkett ER. Early effects of continuous low-dosage all-norgestrel administered alone or with estrogen. Maturitas. 1994;18(3):207-219. DOI: 10.1016/0378-5122(94)90127-9
Smith GI, Reeds DN, Okunade AL, et al. Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women. J Clin Endocrinol Metab. 2014;99(7):E1306-E1310. DOI: 10.1210/jc.2013-4470
Haukeland JW, Damås JK, Konopski Z, et al. Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2. J Hepatol. 2006;44(6):1167-1174. DOI: 10.1016/j.jhep.2006.02.011
Naugler WE, Sakurai T, Kim S, et al. Gender disparity in liver cancer due to sex differences in MyD88- dependent IL-6 production (published correction appears in Science. 2009 Dec 4;326(5958):1346). Science. 2007;317(5834):121-124. DOI: 10.1126/science.1140485
Benedusi V, Martini E, Kallikourdis M, et al. Ovariectomy shortens the life span of female mice. Oncotarget. 2015;6(13):10801-10811. DOI: 10.18632/oncotarget.2984
Mody A, White D, Kanwal F, Garcia JM. Relevance of low testosterone to non-alcoholic fatty liver disease. Cardiovasc Endocrinol. 2015;4(3):83-89. DOI: 10.1097/XCE.0000000000000057
Jaruvongvanich V, Sanguankeo A, Riangwiwat T, Upala S. Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis. Ann Hepatol. 2017;16(3):382-394. DOI: 10.5604/16652681.1235481
Janssen I, Powell LH, Kazlauskaite R, Dugan SA. Testosterone and visceral fat in midlife women: the Study of Women's Health Across the Nation (SWAN) fat patterning study. Obesity (Silver Spring). 2010;18(3):604-610. DOI: 10.1038/oby.2009.251
Rosenbaum M, Nicolson M, Hirsch J, et al. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab. 1996;81(9):3424-3427. DOI: 10.1210/jcem.81.9.8784109
Hossain IA, Akter S, Rahman MK, Ali L. Gender Specific Association of Serum Leptin and Insulinemic Indices with Nonalcoholic Fatty Liver Disease in Prediabetic Subjects. PLoS One. 2015;10(11):e0142165. DOI: 10.1371/journal.pone.0142165
Tsochatzis E, Papatheodoridis GV, Archimandritis AJ. The evolving role of leptin and adiponectin in chronic liver diseases (published correction appears in Am J Gastroenterol. 2006 Dec;101(12):2915). Am J Gastroenterol. 2006;101(11):2629-2640. DOI: 10.1111/j.1572-0241.2006.00848.x
Chitturi S, Farrell G, Frost L, et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? (published correction appears in Hepatology 2002 Nov;36(5):1307) (published correction appears in Hepatology 2002 Oct;36(4 Pt 1):1034). Hepatology. 2002;36(2):403-409. DOI: 10.1053/jhep.2002.34738
Bugianesi E, Gastaldelli A, Vanni E, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia. 2005;48(4):634-642. DOI: 10.1007/s00125-005-1682-x
Woods SC, Gotoh K, Clegg DJ. Gender differences in the control of energy homeostasis. Exp Biol Med (Maywood). 2003;228(10):1175-1180. DOI: 10.1177/153537020322801012
Couillard C, Mauriège P, Prud'homme D, et al. Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease. Diabetologia. 1997;40(10):1178-1184. DOI: 10.1007/s001250050804
Kang SS, Wong PW, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr. 1992;12:279-298. DOI: 10.1146/annurev.nu.12.070192.001431
Luo X, Xiao L, Yang H, et al. Homocysteine downregulates gene expression of heme oxygenase-1 in hepatocytes. Nutr Metab (Lond). 2014;11(1):55. DOI: 10.1186/1743-7075-11-55
Gambacciani M, Mannella P. Homocysteine, menopause and cardiovascular disease. Menopause Int. 2007;13(1):23-26. DOI: 10.1258/175404507780456728
Озолиня Л.А., Лапина И.А., Игнатченко О.Ю., и др. Гипергомоцистеинемия и репродуктивная функция // Вестник Российского государственного медицинского университета. 2010. № 4. С. 46-49. [Ozolinya LA, Lapina IA, Ignatchenko OY, et al. Hyperhomocysteinemia and reproductive function. Bulletin of Russian State Medical University. 2010;(4):46-49. (in Russ)]
Huang RF, Hsu YC, Lin HL, Yang FL. Folate depletion and elevated plasma homocysteine promote oxidative stress in rat livers. J Nutr. 2001;131(1):33-38. DOI: 10.1093/jn/131.1.33
Takahashi T, Morita K, Akagi R, Sassa S. Heme oxygenase-1: a novel therapeutic target in oxidative tissue injuries. Curr Med Chem. 2004;11(12):1545-1561. DOI: 10.2174/0929867043365080
Xu K, Zhao X, Fu X, et al. Gender effect of hyperuricemia on the development of nonalcoholic fatty liver disease (NAFLD): A clinical analysis and mechanistic study. Biomed Pharmacother. 2019;117:109158. DOI: 10.1016/j.biopha.2019.109158
Hak AE, Curhan GC, Grodstein F, et al. Menopause, postmenopausal hormone use and risk of incident gout. Ann Rheum Dis. 2010;69(7):1305-1309. DOI: 10.1136/ard.2009.109884
Lonardo A, Mantovani A, Lugari S, et al. NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management. Int J Mol Sci. 2019;20(11):2841. DOI: 10.3390/ijms20112841
Bozdag G, Mumusoglu S, Zengin D, et al. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841-2855. DOI: 10.1093/humrep/dew218
Anagnostis P, Tarlatzis BC, Kauffman RP. Polycystic ovarian syndrome (PCOS): Long-term metabolic consequences. Metabolism. 2018;86:33-43. DOI: 10.1016/j.metabol.2017.09.016
Broekmans FJ, Knauff EA, Valkenburg O, et al. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG. 2006;113(10):1210-1217. DOI: 10.1111/j.1471-0528.2006.01008.x
Targher G, Rossini M, Lonardo A. Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis? Endocrine. 2016;51(2):211-221. DOI: 10.1007/s12020-015-0640-8
Wu J, Yao XY, Shi RX, et al. A potential link between polycystic ovary syndrome and non-alcoholic fatty liver disease: an update meta-analysis. Reprod Health. 2018;15(1):77. DOI: 10.1186/s12978-018-0519-2
Kumarendran B, O'Reilly MW, Manolopoulos KN, et al. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med. 2018;15(3):e1002542. DOI: 10.1371/journal.pmed.1002542
Sarkar M, Terrault N, Chan W, et al. Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis. Liver Int. 2020;40(2):355-359. DOI: 10.1111/liv.14279
Sarkar M, Wellons M, Cedars MI, et al. Testosterone Levels in Pre-Menopausal Women are Associated With Nonalcoholic Fatty Liver Disease in Midlife. Am J Gastroenterol. 2017;112(5):755-762. DOI: 10.1038/ajg.2017.44
Baptiste CG, Battista MC, Trottier A, Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2010;122(1-3):42-52. DOI: 10.1016/j.jsbmb.2009.12.010
Baranova A, Tran TP, Afendy A, et al. Molecular signature of adipose tissue in patients with both nonalcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS). J Transl Med. 2013;11:133. DOI: 10.1186/1479-5876-11-133
Schiffer L, Kempegowda P, Arlt W, O'Reilly MW. MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease. Eur J Endocrinol. 2017;177(3):R125-R143. DOI: 10.1530/EJE-17-0124
Yuan L, Kardashian A, Sarkar M. NAFLD in women: Unique pathways, biomarkers and therapeutic opportunities. Curr Hepatol Rep. 2019;18(4):425-432. DOI: 10.1007/s11901-019-00495-9.

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