Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)6910.18786/2072-0505-2015-1-60-66THE PROBLEM OF OBESITYПРОБЛЕМЫ ОЖИРЕНИЯOBESITY AS A RISK FACTOR FOR NON-ALCOHOLIC FATTY LIVER DISEASEОЖИРЕНИЕ КАК ФАКТОР РИСКА НЕАЛКОГОЛЬНОЙ ЖИРОВОЙ БОЛЕЗНИ ПЕЧЕНИPavlenkoO. A.ПавленкоО. А.
Russian Federation

Pavlenko Olga Alekseevna – MD, PhD, Professor, Department of Endocrinology and Diabetology

* 81–7 Tverskaya ul.,Tomsk, 634041,Russian Federation. E-mail: pavlenko.51@mail.ru

Павленко Ольга Алексеевна – доктор медицинских наук, профессор кафедры эндокринологии и диабетологии

* 634041, г. Томск, ул. Тверская, 81–7, Российская Федерация. E-mail: pavlenko.51@mail.ru

pavlenko.51@mail.ruSiberian State Medical University, TomskСибирский государственный медицинский университет, Томск2012201511Supplement 1Спецвыпуск 160661202201612022016Copyright ©; 2015, Pavlenko O.A.Copyright ©; 2015, Павленко О.А.2015Pavlenko O.A.Павленко О.А.https://creativecommons.org/licenses/by/4.0https://almclinmed.ru/jour/article/view/69

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disorder associated with obesity and metabolic syndrome. The main pathophysiological factor of liver steatosis is insulin resistance that may lead to development of type 2 diabetes mellitus. Overcoming of insulin resistance by means of body weight reduction and administration of insulin sensitizers is considered to be a promising approach to NAFLD treatment. In accordance with the Russian guidelines on diagnostics and treatment of NAFLD, sibutramine is the drug of choice for medical treatment of obesity. As for insulin sensitizers, metformin (biguanide class) is widely used for treatment of NAFLD in everyday clinical practice. Treatment of NAFLD as a component of metabolic syndrome should be multifactorial and aimed at different aspects of the disease pathophysiology. 

Неалкогольная жировая болезнь печени (НАЖБП)  – широко распространенное заболевание, ассоциированное с  ожирением и  метаболическим синдромом. Основным патогенетическим фактором развития стеатоза печени служит инсулинорезистентность, которая может привести к  развитию сахарного диабета 2-го типа. Преодоление инсулинорезистентности путем снижения массы тела и назначения инсулиносенситайзеров считается перспективным направлением лечения НАЖБП. Согласно российским методическим рекомендациям по лечению и  диагностике НАЖБП, препаратом выбора для фармакотерапии ожирения является сибутрамин. В  качестве инсулиносенситайзеров при лечении НАЖБП в  широкой клинической практике применяется препарат из группы бигуанидов метформин. Лечение НАЖБП, рассматриваемой в  рамках метаболического синдрома, должно быть комплексным, затрагивающим различные звенья формирования болезни. 

non-alcoholic fatty liver disease, obesity, metabolic syndrome, diabetes mellitus, blood lipids, steatosis, glycaemia, sibutramine, metforminнеалкогольная жировая болезнь печени, ожирение, метаболический синдром, сахарный диабет, липиды крови, стеатоз, гликемия, сибутрамин, метформин1. Charlton M. Nonalcoholic fatty liver disease: a review of current understanding and future impact. Clin Gastroenterol Hepatol. 2004;2(12):1048–58.2.De Alwis NM, Day CP. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008;48 Suppl 1:S104–12.3. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology. 2009;49(1): 306–17.4. Brea A, Mosquera D, Martín E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study. Arterioscler Thromb Vasc Biol. 2005;25(5):1045–50.5.Драпкина О, Смирин В, Ивашкин В. Сахарный диабет как фактор риска неалкогольной жировой болезни печени. Врач. 2010;(3):2–4. (Drapkina O, Smirin V, Ivashkin V. [Diabetes mellitus as a risk factor of non-alcoholic fatty liver disease]. Vrach. 2010;(3):2–4. Russian).6. Маев ИВ, Цуканов ВВ, Лукичева ЭВ, Самсонов АА, Васютин АВ, Никушкина ИН. Распространенность, патогенез и принципы лечения неалкогольной жировой болезни печени. Фарматека. 2011;(12):12–5. (Maev IV, Tsukanov VV, Lukicheva EV, Samsonov AA, Vasyutin AV, Nikushkina IN. [Prevalence, pathogenesis and principles of treatment of nonalcoholic fatty liver disease]. Farmateka. 2011;(12):12–5. Russian).7.Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–21.8.Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346(16):1221–31.9. Lee RG. Nonalcoholic steatohepatitis: a study of 49 patients. Hum Pathol. 1989;20(6):594–8. 10. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55(7):434–8.11. Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology. 1990;11(1):74–80.12.Драпкина ОМ, Корнеева ОН, Ивашкин ВТ. Терапия неалкогольного стеатогепатита при метаболическом синдроме: фокус на эссенциальные фосфолипиды. Лечащий врач. 2010;(2). Доступно на: http://www.lvrach. ru/2010/02/12157759/ (Drapkina OM, Korneeva ON, Ivashkin VT. [Treatment of non-alcoholic steatohepatitis in metabolic syndrome: focus on essential phospholipids]. Lechashchiy vrach. 2010;(2). Available at: http://www.lvrach. ru/2010/02/12157759/ Russian).13. Корнеева ОН, Драпкина ОМ. Неалкогольная жировая болезнь печени у пациентов с метаболическим синдромом. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2007; 17(1 Прилож. 29):65. (Korneeva ON, Drapkina OM. [Non-alcoholic fatty liver disease in patients with metabolic syndrome]. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii. 2007; 17(1 Suppl 29):65. Russian).14.Ding X, Saxena NK, Lin S, Gupta NA, Anania FA. Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology. 2006;43(1):173–81.15. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med. 1999;107(5):450–5.16.Драпкина OM, Тутнов ДА. Особенности лечения артериальной гипертензии у больных с заболеваниями печени. Российские медицинские вести. 2008;(3):43–8. (Drapkina OM, Tutnov DA. [Treatment particulars in arterial hypertension in patients with liver disorders]. Rossiyskie meditsinskie vesti. 2008;(3):43–8. Russian).17. You M, Crabb DW. Recent advances in alcoholic liver disease II. Minireview: molecular mechanisms of alcoholic fatty liver. Am J Physiol Gastrointest Liver Physiol. 2004;287(1):G1–6.18.Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 2003;38(4):1008–17.19. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology. 2002;122(6):1649–57.20. Zheng S, Hoos L, Cook J, Tetzloff G, Davis H Jr, van Heek M, Hwa JJ. Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice. Eur J Pharmacol. 2008;584(1):118–24. 21.Adams LA, Angulo P, Lindor KD. Nonalcoholic fatty liver disease. CMAJ. 2005;172(7):899–905.22. de Marco R, Locatelli F, Zoppini G, Verlato G, Bonora E, Muggeo M. Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care. 1999;22(5):756–61.23. Tolman KG, Dalpiaz AS. Treatment of nonalcoholic fatty liver disease. Ther Clin Risk Manag. 2007;3(6):1153–63.24. Petta S, Muratore C, Craxì A. Non-alcoholic fatty liver disease pathogenesis: the present and the future. Dig Liver Dis. 2009;41(9): 615–25.25. Zivkovic AM, German JB, Sanyal AJ. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr. 2007;86(2): 285–300.26.Драпкина OM, Буеверова ЕЛ, Ивашкин ВТ. Атерогенная дислипидемия и печень. Российские медицинские вести. 2008;(1): 17–23. (Drapkina OM, Bueverova EL, Ivashkin VT. [Atherogenic dyslipidemia and liver]. Rossiyskie meditsinskie vesti. 2008;(1):17–23. Russian).27.Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–21.28.Ивашкин ВТ, Драпкина ОМ. Рекомендации по диагностике и лечению неалкогольной жировой болезни печени (НАЖБП). М.; 2012. 12 c. (Ivashkin VT, Drapkina OM. Guidelines on diagnostics and treatment of non-alcoholic fatty liver disease (NAFLD). Moscow; 2012. 12 p. Russian).29. Мехтиев СН, Гриневич ВБ, Кравчук ЮА, Бращенкова АВ. Неалкогольная жировая болезнь печени: клиника, диагностика и лечение. Лечащий врач. 2008;(2). Доступно на: http://www.lvrach.ru/2008/02/4829117/ (Mekhtiev SN, Grinevich VB, Kravchuk YuA, Brashchenkova AV. [Non-alcoholic fatty liver disease: clinical manifestation, diagnostics and treatment]. Lechashchiy vrach. 2008;(2). Available at: http://www.lvrach. ru/2008/02/4829117/ Russian).30.Adams LA, Angulo P. Treatment of nonalcoholic fatty liver disease. Postgrad Med J. 2006;82(967):315–22.31.Драпкина ОМ, Клименков АВ, Ивашкин ВТ. Можно ли назначать статины пациентам с патологией печени? Русский медицинский журнал. 2007;15(2):74–9. (Drapkina OM, Klimenkov AV, Ivashkin VT. [Can statins be administered to patients with liver diseases?]. Russkiy meditsinskiy zhurnal. 2007;15(2):74–9. Russian).32. Lee SS, Park SH, Kim HJ, Kim SY, Kim MY, Kim DY, Suh DJ, Kim KM, Bae MH, Lee JY, Lee SG, Yu ES. Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol. 2010;52(4):579–85.33. Beaugrand M, de Ledinghen V, Douvin C, Marcellin P, Poupon R, Fournier C, Sandrin L, Miette V, Sasso M. Validation of Controlled Attenuation Parameter (CAP) as a non-invasive marker of steatosis in 228 patients with chronic liver disease from various causes. J Hepatol. 2010;52(Suppl 1):S35–6.34. Корнеева ОН, Драпкина ОМ, Павлов ЧС, Бакулин ИГ, Ивашкин ВТ. Неалкогольный стеатогепатит при метаболическом синдроме. Consilium medicum (Прилож. Гастроэнтерология). 2007;(2):18–21. (Korneeva ON, Drapkina OM, Pavlov ChS, Bakulin IG, Ivashkin VT. [Non-alcoholic steatohepatitis in metabolic syndrome]. Consilium medicum (Suppl. Gastroenterology). 2007;(2):18–21. Russian).35. Задионченко ВС, Адашева ТВ, Демичева ОЮ, Ромашкин АВ, Заседателева ЛВ. Метаболический синдром и ожирение. Артериальная гипертония при метаболическом синдроме: патогенез, основы терапии. Consilium medicum. 2004;6(9):663–8. (Zadionchenko VS, Adasheva TV, Demicheva OYu, Romashkin AV, Zasedateleva LV. [Metabolic syndrome and obesity. Arterial hypertension in metabolic syndrome: pathophysiology and basics of treatment]. Consilium medicum. 2004;6(9):663–8. Russian).36. Lowyck I, Fevery J. Statins in hepatobiliary diseases: effects, indications and risks. Acta Gastroenterol Belg. 2007;70(4):381–8.37. Spadaro L, Magliocco O, Spampinato D, Piro S, Oliveri C, Alagona C, Papa G, Rabuazzo AM, Purrello F. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig Liver Dis. 2008;40(3): 194–9.38. Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol. 2008;42(4):413–8.39.Andersen T, Gluud C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol. 1991;12(2):224–9.40. Cave M, Deaciuc I, Mendez C, Song Z, JoshiBarve S, Barve S, McClain C. Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem. 2007;18(3):184–95.41.Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, Emick D, Lok AS, Conjeevaram HS. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol. 2005;100(5):1072–81.42. Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes. 2005;54(3):603–8.43.Dixon JB, Bhathal PS, Hughes NR, O'Brien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology. 2004;39(6):1647–54.44.Harrison SA, Fincke C, Helinski D, Torgerson S, Hayashi P. A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther. 2004;20(6):623–8.45. Ishibashi E, Eguchi Y, MizutaT, Kitajima Y, Oza N, Nakashita S, Matsunobu A, Takahashi H, Kawaguchi Y, Ozaki I, Iwakiri R, Eguchi T, Ono N, Fujimoto K. The change in serum aminotransferase level achieved by weight reduction predicts the improvement of liver steatosis in patients with nonalcoholic fatty liver disease. 44th Annual Meeting of the European Association for the Study of the Liver 2009. 4.22–26 Copenhagen, Denmark. J Hepatol. 2009;50 Suppl 1:S360.46. Sabuncu T, Nazligul Y, Karaoglanoglu M, Ucar E, Kilic FB. The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis. Rom J Gastroenterol. 2003;12(3): 189–92.47. Tambascia MA, Geloneze B, Repetto EM, Geloneze SR, Picolo M, Magro DO. Sibutramine enhances insulin sensitivity ameliorating metabolic parameters in a double-blind, randomized, placebo-controlled trial. Diabetes Obes Metab. 2003;5(5):338–44.48. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N. Metformin in non-alcoholic steatohepatitis. Lancet. 2001;358(9285):893–4.49. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005;100(5):1082–90.50.Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A, Yesilova Z, Gulsen M, Dagalp K. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2004;19(5):537–44.51.Nair S, Diehl AM, Wiseman M, Farr GH Jr, Perrillo RP. Metformin in the treatment of nonalcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004;20(1):23–8.52. Schwimmer JB, Middleton MS, Deutsch R, Lavine JE. A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2005;21(7):871–9.53.Ивашкин ВТ, Драпкина ОМ, Шульпекова ЮО. Диагностика и лечение неалкогольной жировой болезни печени. Методические рекомендации. Российские медицинские вести. 2009;(3):70. (Ivashkin VT, Drapkina OM, Shul'pekova YuO. [Diagnostics and treatment of non-alcoholic fatty liver disease. Methodical recommendations]. Rossiyskie meditsinskie vesti. 2009;(3):70. Russian).54. Lutchman G, Modi A, Kleiner DE, Promrat K, Heller T, Ghany M, Borg B, Loomba R, Liang TJ, Premkumar A, Hoofnagle JH. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology. 2007;46(2):424–9.55.De Lusong MA, Labio E, Daez L. Metformin in the treatment of non-alcoholic fatty liver disease: a meta-analysis. Phil J Gastroenterology. 2006;(2):53–63.