310 Mira Street, Stavropol, Russia, 355017
+7 8652 352524; +7 8652 353229.
+7 8652 352524.
The journal is included into The list of leading scientific periodicals.
The aim of the study was to determine the clinical significance of the blood levels of endothelin-1 (E-1) and nitric oxide (NO) as indicators of endothelial function, as well as serum endotoxin (ET) in patients with non-alcoholic fatty liver disease (NAFLD). The body of patients included 142 persons with NAFLD – 90 patients with hepatic steatosis (Group I), 52 patients with non-alcoholic steatohepatitis (NASH) (Group II). All the patients had their plasma content of E-1 determined by ELISA, as well as the level of NO (by colorimetric method). The level of ET in blood serum was determined employing the chromogenic method Hbt LAL. The values for endothelial dysfunction (ED) in the group of the patients with steatosis revealed no difference from the control values. The content of E-1 and NO in the blood of the patients with NASH exceeded those in healthy individuals and in Group I. The ET levels in the blood of the patients in Group II were higher compared to the healthy persons as well the patients with hepatic steatosis. There has been positive correlation identified between the E-1 and HOMA-index, E-1 and ET in case of NASH, yet not in Group I. The dynamics of 1 month into the therapy, which included dietary measures, Metformin and hepatoprotector, revealed a decrease in the blood levels of E-1 and no change in NO. The outcomes demonstrate a role of ED and endotoxinemia in the progress from steatosis to steatohepatitis. It has been shown that, in case of NASH, comprehensive therapy may exert positive effect on endothelial function.
1. Bookman I. D., Pham J., Guindi M., Heathcote E. J. Distinguishing nonalcoholic steatohepatitis from fatty liver: serum-free fatty acids, insulin resistance, and serum lipoproteins. Liver Int. 2006;26:566–571.
2. Chalasani N., Younossi Z., Lavine J. E., Diehl A. M. et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the american gastroenterological association, american association for the study of liver diseases, and american college of gastroenterology. Hepatology. 2012;55:2005–2023.
3. Day C. P., James O. F. Steatohepatitis: a tale of two «hits»? Gastroenterology. 1998;114:842-845.
4. Degertekin B., Ozenirler S., Elbeg S., Akyol G. The serum endothelin-1 level in steatosis and NASH, and its relation with severity of liver fibrosis. Dig. Dis. Sci. 2007;52(10):2622-2628.
5. Festi D., Colecchia A., Sacco T., Bondi M. et al. Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obes Rev. 2004;(5):27–42.
6. Fujita K., Nozaki Y., Yoneda M., Vada K. et al. Nitric oxide plays a crucial role in the development/progression of nonalcoholic steatohepatitis in the choline-deficient, l-amino acid-defined diet-fed rat model. Alcohol Clin Exp Res. 2010;34(Suppl 1):S18-24.
7. Harte A. L., da Silva N. F., Creely S. J., McGee K. C. et al. Elevated endotoxin levels in non-alcoholic fatty liver disease. J Inflamm. 2010;30:7-15.
8. Koruk M., Taysi S., Savas M. C., Yilmaz O. et al. Oxidative Stress and Enzymatic Antioxidant Status in Patients with Nonalcoholic Steatohepatitis. Ann Clin Lab Sci. 2004;34(1):57-62.
9. Lteif A., Vaishnava P., Baron A. D., Mather K. J. Endothelin limits insulin action in obese/insulin-resistant humans. Diabetes. 2007;56(3):728–734.
10. Machado M. V., Cortez-Pinto H. Gut microbiota and nonalcoholic fatty liver disease. Annals of Hepatology. 2012;11(4):440-449.
11. Malaguarnera M., Rosa, M. D., Nicoletti, F., Malaguarnera, L. Molecular mechanisms involved in NAFLD progression. J. Mol. Med. 2009;87:679–695.
12. Mather J. K., Steinberg O. H., Baron D. A. Insulin resistance in the vasculature. J Clin Invest. 2013;123(3):1003–1004.
13. Pradere J. P., Troeger J. S., Dapito D. H., Mencin A. A. et al. Toll-like receptor 4 and hepatic fibrogenesis. Semin Liver Dis. 2010;30:232–244.
14. Senturk O., Kosoman O., Hulagu S., Sahin T. et al. J. Endothelial dysfunction in Turkish patients with non-alcoholic fatty liver disease. Internal Medicine Journal. 2008;38:183–189.
15. Souza M. R., Diniz M. F., Medeiros-Filho J. E., Araújo M. S. Metabolic syndrome and risk factors for non-alcoholic fatty liver disease. Arq. Gastroenterol. 2012;49(1):89–96.
16. Steinberg H. O., Chaker H., Leaming R., Johnson A. et al. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996;97(11):2601–2610.
17. Su L., Wang J. H., Cong X., Wang L. H. et al. Intestinal immune barrier integrity in rats with nonalcoholic hepatic steatosis and steatohepatitis. Chin Med J. 2012;125(2):306-311.
18. Torer N., Ozenirler S., Yusel A., Bukan N. et al. Importance of cytokines, oxidative stress and expression of BLC-2 in the pathogenesis of nonalcoholic steatohepatitis. Scandinavian J. of Gastroenterol. 2007;42(9):1095–1101.
19. Villanova N., Moscatiello S., Ramilli S., Bugianesi E. et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005;42:473–480.
20. Yang Y. Y., Tsai T. H., Huang Y. T., Lee T. Y. et al. Hepatic endothelin-1 and endocannabinoids-dependent effects of hyperleptinemia in nonalcoholic steatohepatitis-cirrhotic rats. Hepatology. 2012;55(5):1540-1550.
21. Yildirim A., Soylu Ö., Aydin A., Güveli H. et al. The relationship between endothelial dysfunction and serum aminotransferase levels in nonalcoholic fatty liver disease. Türk Kardiyol Dern Arş – Arch Turk Soc Cardiol. 2007;35(6):354-359.
22. Zhao C. X., Xu X., Cui Y., Wang P. et al. Increased endothelial nitric-oxide syntase expression reduces hypertension and hyperinsulinemia in fructose-treated rats. J Pharmacol Exp Ther. 2009;328(2):610-620.
Keywords: non-alcoholic fatty liver disease, steatosis, nonalcoholic steatohepatitis, endothelial dysfunction, endotoxinemia