Pharmacotherapy of non-alcoholic fatty liver disease: focus on fibrosis
M.E. Statsenko, S.V. Turkina, N.N. Shilina, E.E. Gorbachev, A.A. Ermolenko
Volgograd State Medical University
Aim: to evaluate the effect of taurine on the severity of liver fibrosis, the structural and functional parameters of the liver in patients with non-alcoholic fatty liver disease (NAFLD).
Patients and Methods: 60 patients with NAFLD diagnosed according to the evaluation of liver ultrasound (using SIEMENS SONOLINE G50 device, Germany, with a Doppler sensor with an assessment of hepatic parenchymal echogenicity, vascular pattern, echo attenuation rate) and liver fibrosis index NFS>0, 675 (F3–4 fibrosis), underwent a prospective comparative randomized study. The patients were divided into 2 groups using the simple randomization method: group 1 (main) — patients with NAFLD who took taurine in a daily dose of 1000 mg (double intake of 500 mg/day) in addition to the basic treatment of concomitant diseases (type 2 diabetes mellitus, ischemic heart disease, hypertension); group 2 (control) — patients with NAFLD took only the drugs of basic therapy for concomitant diseases.
Initially and after 24 weeks of treatment, the content of type IV collagen in the blood was examined, the Fatty Liver Index (FLI) and the NAFLD Fibrosis Score (NFS) were calculated. The state of carbohydrate metabolism was controlled according to the level of fasting glucose, basal insulin was determined, and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. The levels of total cholesterol, triglycerides, low-density and high-density lipoproteins were determined to control the state of blood lipid metabolism. The activity of alanine and aspartic aminotransferase, g-glutamyl transpeptidase was studied to assess the damage markers and the functional state of the liver.
Results: at the end of 24-week treatment with taurine in patients with NAFLD and liver fibrosis, a statistically significant decrease in type IV collagen, a decrease in the NFS at all stages of fibrotic changes, and a statistically significant decrease in the early stages of fibrosis (NFS≤0.675) were noted. A pronounced metabolic activity of the drug was revealed manifested with hypoglycemic and lipid-lowering effects as well as significant reduction in the severity of insulin resistance.
Key words: non-alcoholic fatty liver disease, taurine, liver fibrosis score, type IV collagen, structural and functional characteristics.
For citation: Statsenko M.E., Turkina S.V., Shilina N.N. et al. Pharmacotherapy of non-alcoholic fatty liver disease: focus
on fibrosis // RMJ. Medical Review. 2018. № 7(II). P. 59–63.
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23. Стаценко М.Е., Туркина С.В., Шилина Н.Н. Поражение печени у больных с хронической сердечной недостаточностью ишемического генеза и сахарным диабетом типа 2 — коварный тандем: возможности дополнительной органопротективной терапии // Consilium Medicum. 2016. T.18 (5). C.103–109 [Stacenko M.E., Turkina S.V., Shilina N.N. Porazhenie pecheni u bolnyh s hronicheskoj serdechnoj nedostatochnostyu ishemicheskogo geneza i saharnym diabetom tipa 2 — kovarnyj tandem: vozmozhnosti dopolnitelnoj organoprotektivnoj terapii // Consilium Medicum. 2016. T.18(5). C.103–109 (in Russian)].
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25. Gentile C.L., Nivala A.M., Gonzales J.C. et al. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease // Am J. Regul Integr Comp Physiol. 2011. Vol. 301(6). P.1710–1722.
2. Ивашкин В.Т., Драпкина О.М., Маев И.В. и др. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлинической практики в Российской Федерации: результаты исследования DIREG 2 // РЖГГК. 2015. T.6. C.31–42 [Ivashkin V.T., Drapkina O.M., Maev I.V. i dr. Rasprostranennost nealkogolnoi zhirovoi bolezni pecheni u pacientov ambulatorno-poliklinicheskoi praktiki v Rossiiskoi Federacii: rezultaty issledovaniya DIREG 2 // RZhGGK. 2015. T.6. C.31–42 (in Russian)].
3. Patil R., Sood G.K. Non-alcoholic fatty liver disease and cardiovascular risk // World J. Gastrointest Pathophysiol 2017. Vol. 8(2). P.51–58.
4. Arulanandan A., Ang B., Bettencourt R. et al. Association Between Quantity of Liver Fat and Cardiovascular Risk in Patients With Nonalcoholic Fatty Liver Disease Independent of Non-alcoholic Steatohepatitis // Clin Gastroenterol Hepatol. 2015. Vol. 13. P.1513–1520.
5. Söderberg C., StDal P., Askling J. et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up // Hepatology. 2010. Vol. 51. P.595–602.
6. Sinn D.H., Kang D., Jang H.R. et al. Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: A cohort study // J. Hepatol. 2017. Vol. 67(6). P.1274–1280.
7. Lonardo A., Ballestri S., Guaraldi G. et al. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease — Evidence from three different disease models: NAFLD, HCV and HIV // World J. Gastroenterol. 2016. Vol. 22(44). P.9674–9693.
8. Ekstedt M., Hagstrom H., Nasr P. et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up // Hepatology. 2015. Vol. 61. Р.1547–1554.
9. Hagström H., Nasr P., Ekstedt M. et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD // J. Hepatol. 2017. Vol. 67(6). P.1265–1273.
10. EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. European Association for the Study of the Liver (EASL) and European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) // Diabetologia. 2016. Vol. 59. P.1121–1140.
11. Weiskirchen R. Hepatoprotective and Anti-fibrotic Agents: It’s Time to Take the Next Step // Front Pharmacol. 2015. Vol. 6. P.303–343.
12. Schaffer S.W., Azuma J., Mozaffari M. Role of antioxidant activity of taurine in diabetes // Can J Physiol Pharmacol. 2009. Vol. 87(2). P.91–99.
13. Barua M., Liu Y., Quinn M.R. Taurine chloramine inhibits inducible nitric oxide synthase and TNF-alpha gene expression in activated alveolar macrophages: decreased NF-kappaB activation and IkappaB kinase activity // J. Immunol. 2001. Vol. 167(4). P.2275–2281.
14. Li M., Reynolds C.M., Sloboda D.M. et al. Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity // PLoS One. 2013. Vol. 8(10). P.e769.
15. Abdel-Moneim A.M., Al-Kahtani M.A., El-Kersh M.A., Al-Omair M.A. Free Radical Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage // PLoS One. 2015. Vol. 10(12). P.e0144509.
16. De la Puerta C., Arrieta F.J., Balsa J.A. et al. Taurine and glucose metabolism: a review // Nutr Hosp. 2010. Vol. 25. P.910–919.
17. Militante J.D., Lombardini J.B. Dietary taurine supplementation: hypolipidemic and antiatherogenic effects // Nutr Res. 2004. Vol. 24. P.787–801.
18. Putnam K., Shoemaker R., Yiannikouris F., Cassis L.A. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome // Am J. Physiol Heart Circ Physiol. 2012. Vol. 30. P.H1219–1230.
19. Нano T., Kasano M., Tomari H., Iwane N. Taurine suppresses pressor response through the inhibition of sympathetic nerve activity and the improvement in baro-reflex sensitivity of spontaneously hypertensive rats // Adv. Exp. Med. Biol. 2009. Vol. 643. P.57–63.
20. Ergü n YDlmaz. The diagnostic role of ultrasonograhyy in liver streatosis // Turkish J. Gastroenterol. 1999. Vol. 2. P.96–100.
21. Angulo P., Hui J.M., Marchesini G. et al. The NAFLD Fibrosis Score: A Noninvasive System That Identifies Liver Fibrosis in Patients with NAFLD // Hеpatology. 2007. Vol. 45 (4). P.846–854.
22. Bedogni G., Bellentani S., Miglioli L. et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population // BMC Gastroenterology. 2006. Vol. 6. P.33–38.
23. Стаценко М.Е., Туркина С.В., Шилина Н.Н. Поражение печени у больных с хронической сердечной недостаточностью ишемического генеза и сахарным диабетом типа 2 — коварный тандем: возможности дополнительной органопротективной терапии // Consilium Medicum. 2016. T.18 (5). C.103–109 [Stacenko M.E., Turkina S.V., Shilina N.N. Porazhenie pecheni u bolnyh s hronicheskoj serdechnoj nedostatochnostyu ishemicheskogo geneza i saharnym diabetom tipa 2 — kovarnyj tandem: vozmozhnosti dopolnitelnoj organoprotektivnoj terapii // Consilium Medicum. 2016. T.18(5). C.103–109 (in Russian)].
24. Morling J.R., Fallowfield J.A., Williamson R.M. et al. y-Glutamyltransferase, but not markers of hepatic fibrosis, is associated with cardiovascular disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study // Diabetologia. 2015. Vol. 58. P.1484–1493.
25. Gentile C.L., Nivala A.M., Gonzales J.C. et al. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease // Am J. Regul Integr Comp Physiol. 2011. Vol. 301(6). P.1710–1722.
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