Options of dyslipidemia treatment at non-alcoholic fatty liver disease

Aim of review. To consider different treatment options for dyslipidemia in non-alcoholic fatty liver disease (NAFLD). Summary. NAFLD occurs in 20-30% of adult population. In the Russian Federation its rate is estimated as high as 37,1%. In the most of NAFLD cases severe disorder of lipid metabolism takes place. In large clinical trials it was demonstrated that the dyslipidemia significantly increases cardiovascular risks and worsens life expectancy in these patients. In the present overview treatment options of several therapeutic agents for dyslipidemia treatment at NAFLD are discussed: phenofibrate, omega-3 polyunsaturated fatty acids (omega-3-PUFAs) and S-adenosylmethionine (SAM). Results of numerous experiments and several clinical trials form the basis for phenofibrate administration for NAFLD patients. In animal experiments the positive role of phenofibrate as PPARα agonist was demonstrated (Peroxisome proliferator activated receptor alpha) for NAFLD prevention and treatment. Results of several studies published at the moment demonstrate that at NAFLD lipid metabolism markers, and serum transaminase levels normalize, sensitivity to insulin increases, the liver histology pattern improves at phenofibrate treatment. Specification of efficacy and safety of application of the drug requires more large-scale clinical studies. Omega-3-PUFAs is one more option in the lipid metabolism disorders treatment in this group of patients. These substances play important role in lipid metabolism regulating expression of the genes (including PPARα) involved in lipid and glucose metabolism. Available clinical trials demonstrate high therapeutical effect of these agents at NAFLD. In the review results of the experimental studies investigating the role of SAM in NAFLD pathogenesis and disorders of lipid metabolism is presented. Conclusion. Now data on a pathogenesis of lipid metabolism disorders at NAFLD are accumulated. The bulk of experimental data and series of clinical trials allow to assume positive affect of such drugs as phenofibrate, omega-3-PUFA and SAMe for treatment of dyslipidemia. Further high-grade studies in this area is necessary.

неалкогольная жировая болезнь печени, неалкогольный стеатогепатит, дислипидемия, фенофибрат, омега-3 полиненасыщенные жирные кислоты, S-аденозилметионин

1. Диагностика и лечение неалкогольной жировой болезни печени: Методические рекомендации для врачей / Под ред. В.Т. Ивашкина. М., 2015.

2. Драпкина О.М. Нарушения липидного обмена у больных с неалкогольной жировой болезнью печени. Справочник поликлинического врача 2009; 6:9-13.

3. Bril F., Lomonaco R., Cusi K. The challenge of managing dyslipidemia in patients with non-alcoholic fatty liver disease. Clin Lipidol 2012; 7(4):471-81.

4. Buldak L., Dulawa-Buldak A., et al. Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Int J Clin Pharmacol Ther 2012; 50:805-13.

5. Capanni M., Calella F., Biagini M.R., Genise S., Raimondi L., Bedogni G., et al. Prolonged n3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 2006; 23:1143-51.

6. Chalasani N., Jonnossi Z., Lavine I.E., Diehl A.M., et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American association for the study of liver diseases, American college of gastroenterology, and the American gastroenterological association. Hepatology 2012; 55(6):2005-23.

7. Cong W.N., Tao R.Y., Tian J.Y., Liu G.T., Ye F. The establishment of a novel non-alcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice. Life Sci 2008; 82(19-20):983-90.

8. Di Minno M.N., Russolillo A., et al. Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease. World J Gastroenterol 2012; 7; 18(41):5839-47.

9. El-Haggar S.M., Mostafa T.M. Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease. Hepatol Int 2015; 9(3):471-9.

10. Gandhi N., Lenton R., Bhartia M., Abbas A., Raju J., Ramachandran S. Effect of fibrate treatment on liver function tests in patients with the metabolic syndrome. Springerplus 2014; 3:14.

11. Koh K., Quon M., et al. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Atherosclerosis 2012; 220:537-44.

12. Kostapanos M., Kei A., Elisaf M. Current role of fenofibrate in the prevention and management of nonalcoholic fatty liver disease. World J Hepatol 2013; 5(9):470-8.

13. Li X.M., Li Y., et al. Combination therapy with metformin and fenofibrate for insulin resistance in obesity. J Int Med Res 2011; 39:1876-82.

14. Lin S., Xiao K., Liu Y., et al. Omega-3 polyunsaturated fatty acids for non-alcoholic fatty liver disease. Cochrane Database of Systematic Reviews 2013, Issue 11.

15. Mantena S., King A., Andringa K., et al. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol and obesity induced fatty liver diseases. Free Radic Biol Med 2008; 44(7):1259-72.

16. Martínez-Chantar M.L., Vázquez-Chantada M., Ariz U., Martínez N., Varela M., Luka Z., et al. Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 2008; 47(4):1191-9.

17. Martínez-Uña M., Varela-Rey M., Mestre D., et al. S-adenosylmethionine increases circulating very-low density lipoprotein clearance in non-alcoholic fatty liver disease. J Hepatol 2015; 62:673-81.

18. Mato J., et al. A metabolic difinition of NASH and its resolution by S-adenosylmetionin in MAT1A-Ko mice. J Hepatol 2015; 62:263-864.

19. Noureddin M., Mato J., Lu S. Non-alcoholic fatty liver disease: Update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine.. Exp Biol Med (Maywood) Exp Biol Med 2015:1-12.

20. Parker H., Johnson N., et al. Omega-3 supplementation and non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Hepatol 2012; 56:944-51.

21. Quentin M., Christopher P. S-adenosylmethionine (SAMe) therapy in liver disease: A review of current evidence and clinical utility. J Hepatol 2012; 57 (5):1097- 109.

22. Ratziu V., Bellentani S., Cortez-Pinto H., Day C., Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010; 53:372-3884.

23. Shin S.J., Lim J.H., et al. Peroxisome proliferatoractivated receptor-alpha activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats. Hypertens Res 2009; 32:835-45.

24. Shiri-Sverdlov R., Wouters K., et al. Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates. J Hepatol 2006; 44:732-41.

25. Spadaro L., Magliocco O., et al. Effects of n-3 polyunsaturated fatty acids in subjects with non-alcoholic fatty liver disease. Dig Liver Dis 2008; 40:194-9.

26. Tanaka N., Sano K., Horiuchi A., Tanaka E., Kiyosawa K., Aoyama T. Highly purified eicosapentaenoic acid treatment improves non-alcoholic steatohepatitis. J Clin Gastroenterol 2008; 42:413-8.

27. Targher G., Bertolini L., Rodella S., et al. Non-alcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 2007; 30(8):2119-21.

28. Vendemiale G., Altomare E., et al. Effects of oral S-adenosyl-l-methionine on hepatic/ Glutathione in patients with liver disease. Scand J Gastroenterol 1989; 24:407-15.

29. Zhu F.S., Liu S., Chen X.M., Huang Z.G., Zhang D.W. Effects of n-3 polyunsaturated fatty acids from seal oils on non-alcoholic fatty liver disease associated with hyperlipidemia. World J Gastroenterol 2008; 14:6395-400.