1. The First Moscow State Medical University (Moscow, Russian Federation)

Abstract:The purpose of the review is to analyze modern data on pathogenesis, principles of treatment and future prospects treatment of nonalcoholic fatty liver disease (NAFLD). Modern ideas about the role of insulin resistance, oxidative stress gene polymorphisms in the pathogenesis of disease progression. This has led in recent years to a new strategy of treatment of the disease. Examines the role of physical load, modified diet, the weight loss. Substantiates the primary role of the use of insulin sensitizers, and agents with cytoprotective and antioxidant effect. The lack of the only effective drug for the treatment of NAFLD justifies the appropriateness of the appointment of combination therapy with exposure to various aspects of the pathogenesis. Elaborates on new drugs under clinical study.

• References total 45 ⇓ :: .
  1. Драпкина О. М., Гацолаева Д. С., Ивашкин В. Т. Неалкогольная жировая болезнь печени как компонент метаболического синдрома. //Российские медицинские вести, 2010, том 15, 2. с. 72 - 78
  2. Драпкина О. М., Ивашкин В. Т. Эпидемиологические особенности неалкогольной жировой болезни печени в России. //Российский журнал гастроэнтерологии гепатологии, колопроктологии. 2014, том 24, 4. с. 32 - 38
  3. Ивашкин В. Т., Драпкина О. М. Маев И. В. и др. Рапространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлинической практики в Российской Федерации: результаты исследования DIREG2. //Российский журнал гастроэнтерологии гепатологии, колопроктологии. 2015, том 6, с. 31 - 41
  4. McCullough A. J: Update on nonalcoholic fatty liver disease. J. Clin. Gastroenterol, 2002; 34: 255 - 262
  5. Ludwig J. Viggiano RT., McGill DB., Oh BJ. Nonalcoholic steatohepatitis: Mayo experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980; 55: 434 - 438
  6. Browning JD, et al: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology, 2004; 40:1387 - 1395
  7. Kotronen A. Johansson L. E., Johansson L. M. et. al. A common variant in PNPLA3, which encodes adiponutrin is associated with liver fat content in humans. Diabetologia. 2009; 52 (6): 1056 - 60
  8. Лазебник Л. Б., Звенигородская Л. А. Метаболический синдром и органы пищеварения. - М. Анахарсис, 2009. 184с
  9. de Marco R, Locatelli F, Zoppini G, et. al. Causespecific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care, 1999; 22:756 - 761
  10. Adams LA, Harmsen S, St Sauver JL, et al. Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study. Am. J. Gastroenterol. 2010;105:1567 - 1573.
  11. Zoppini G, Fedeli U, Gennaro N, et al. Mortality from chronic liver diseases in diabetes. Am. J. Gastroenterol. 2014;109:1020 - 1025.
  12. Dixon JB, Bhathal PS, Hughes NR, O’Brien PE. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology 2004;39:1647 - 1654.
  13. Lassailly G, Caiazzo R, Buob D, et al. Effects of bariatric surgery on severe liver injury in morbid obese patients with proven NASH: a prospective study. Hepatology, 2014;60:305A.
  14. Moschen AR, Molnar C, Geiger S, et al. Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor expression. Gut, 2010; 59:1259 - 1264.
  15. Kistler KD, Brunt EM, Clark JM, et al. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am. J. Gastroenterol. 2011;106:460 - 468.
  16. Fealy CE, Haus JM, Solomon TP, et al. Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease. J. Appl. Physiol. 1985;2012:1 - 6.
  17. Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 2002;51:2968 - 2974.
  18. Neuschwander-Teri B. A., et. al. Improved alcoholic steatohepatitis after 48 weeks of treatment the PPAR_γ- ligand rosiglitazone. Hepatology, 2003;38: 1008 - 1017
  19. Ratziu V, Charlotte F, Bernhardt C, et al. Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial. Hepatology, 2010;51:445 - 453.
  20. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 2010;362:1675 - 1685.
  21. Sanyal AJ, Brunt EM, Kleiner DE, et al. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology, 2011;54:344 - 353.
  22. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N. Engl. J. Med. 2006;355:2297 - 2307
  23. Aithal GP, Thomas JA, Kaye PV, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology, 2008;135:1176 - 1184.
  24. Uygun A., Kadayifci A., Isik At. et. al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 2004:19:537 - 544
  25. Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA, 2011;305:1659 - 1668
  26. Bhalla K, Hwang BJ, Dewi RE, et al. Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis. Cancer Prev. Res. (Phila) 2012;5:544 - 552.
  27. Chen HP, Shieh JJ, Chang CC, et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut, 2012;62:606 - 615
  28. Watanabe M, Houten SM, Wang L, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest 2004;113:1408 - 1418
  29. Wagner M, Zollner G, Trauner M. Nuclear bile acid receptor farnesoid X receptor meets nuclear factor-kappaB: new insights into hepatic inflammation. Hepatology, 2008;48:1383 - 1386.
  30. Wang YD, Chen WD, Wang M, et al. Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response. Hepatology 2008; 48:1632 - 1643
  31. Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology, 2013; 145:574 - 582
  32. Staels B, Rubenstrunk A, Noel B, et al. Hepato-protective effects of the dual PPARalpha/delta agonist GFT505 in rodent models of NAFLD/NASH. Hepatology, 2013;58:1941 - 1952.
  33. Cariou B, Hanf R, Lambert-Porcheron S, et al. Dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care, 2013;36:2923 - 2930
  34. Armstrong MJ, Houlihan DD, Rowe IA, et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment. Pharmacol. Ther. 2013;37:234 - 242.
  35. Armstrong MJ, Hull D, Guo K, et al. Effect of liraglutide on adipose insulin resistance and hepatic de-novo lipogenesis in non-alcoholic steatohepatitis: substudy of a phase 2, randomised placebocontrolled trial. Lancet, 2014;383: S21.
  36. Lieber C. S. Alcoholic liver diseas: new in sigths in pathogenesis lead to new treatment//Hepatology. - 2000. - Vol. 32, suppl. 1. - P. 113 - 128.
  37. Sun Cunxu, Zheng Xianling, Tan Zenghuan, Clinical Observation on Polyene Phosphatidyl Choline and Metformin in the Treatment of Type 2 Diabetes and Non-alcoholic Fatty Liver Disease. Clinical Focus, September 5, 2008, Vol. 23, No. 17
  38. Подымова С. Д., Довлетшина И. В. Эффективность применения α-липоевой кислоты (берлитиона) у больных неалкогольным стеатогепатитом Ж. «Экспериментальная и клиническая гастроэнтерология» 2008, N5
  39. Soden JS, Devereaux MW, Haas JE, et al. Subcutaneous vitamin E ameliorates liver injury in anin vivo model of steatocholestasis. Hepatology 2007;46:485 - 495
  40. Daryani N. E., Mirmomen S., Farahvash M. J. et al. Vitamin E the treatment of Patients with NASH: Placebo-controlled Double - Blindstady//GUT, International Journal of Gastroenterology and Hepatology. - 10th UEGW. - Geneva, 2002. - A (15).
  41. Ratzui V., De Ledinghen V., Oberti F. et. al. A randomized controlled trial of higy-dosei ursodeoxycholic asid for nonalcoholic steatohepatitis. J. Hepatol. 2011; 54 (5); 1011 - 19
  42. Leuschner U. F., Lindenthal B., Herrmann G., et. al. Higy-dose ursodeoxycholic asid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. J. Hepatol. 2010; 52 (2); 472 - 79
  43. Haedrich M.,Dufour JF. UDCA for End of the story. J. Hepatol. 2011; 54 (5); 856 - 58.
  44. Adams LA, et al: A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. Am. J. Gastroenterol, 2004; 99:2365 - 2368.
  45. Satapathy SK, et al: Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am. J. Gastroenterol. 2004; 99:1946 - 1952.

Full text is published :
Podymova S.D. THE MODERN VIEW ON PATHOGENESIS AND TREATMENT OF NONALCOHOLIC FATTY LIVER DISEASE. Experimental and Clinical Gastroenterology Journal. 2016;129(05):74-82
Read & Download full text