DOI: https://doi.org/10.22141/2224-0721.14.7.2018.148777

Non-alcoholic fatty liver disease: prevalence, etiology, pathogenesis, approaches to the dіagnosis and therapy (literature review and own data)

O.V. Zemlіanіtsyna, І.P. Dunaeva, V.І. Savenkov, V.M. Sinaіko, Yu.V. Maltseva, N.O. Kravchun

Abstract


The article presents the modern literature data about the prevalence, etiology, pathogenesis of non-alcoholic fatty liver disease in type 2 diabetes mellitus, approaches to the diagnosis and therapy of these patients. The analysis of literature on the risk factors for cardiovascular diseases and cognitive impairment in patients with type 2 diabetes mellitus in non-alcoholic fatty liver disease has been carried out. The role of invasive, minimally invasive and non-invasive methods for assessing the degree of liver fibrosis is shown. The results of own researches, namely determining the features of melatonin excretion in urine and its correlation with the degree of liver fibrosis in patients with type 2 diabetes mellitus in the presence of non-alcoholic fatty liver disease, are given. The results of studying the level of adiponectin in these patients and the role of nutrient therapy to reduce the risk of cardiovascular disorders are presented.


Keywords


type 2 diabetes mellitus; non-alcoholic fatty liver disease; cytokines; adiponectin; leptin; resistin; fibrosis mar­kers; melatonin; review

References


World Health Organization. Global report on diabetes. Geneva: WHO Press; 2016. 88 p.

Mankovsky BN. Actual issues of diabetology in Ukraine. Diabetologija, Tyreoi'dologija, Metabolichni rozlady. Zdorov’ja Ukrai'ny. 2011;(15):6-7. (in Russian).

Biryukova EV, Rodionova SV. Type 2 diabetes and non-alcoholic fatty liver disease are modern diseases. Medical Almanac. 2017;(51):130-135. doi: 10.21145/2499-9954-2017-6-130-135. (in Russian).

Shipovskaia AA, Laryna NA, Kurbatova YV, Dudanova OP. Non-alcoholic fatty liver disease in patients with type 2 diabetes. Gastroenterologia Sankt-Peterburga 2016;(3-4):M23-M24. (in Russian).

LaBrecque D, Abbas Z, Anania F, et al. World Gastroenterology Organization Global Guidelines: Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. J Clin Gastroenterol. 2014 Jul;48(6):467-73. doi: 10.1097/MCG.0000000000000116.

Bakulin IG, Sandler YG, Vinnitskaya EV, Keiyan VA, Rodionova SV, Rotin DL. Diabetes mellitus and non-alcoholic fatty liver disease: the verges of contingency. Ter Arkh. 2017;89(2):59-65. doi: 10.17116/terarkh201789259-65. (in Russian).

Drapkina OM, Smirin VI, Ivashkin VT. Non-alcoholic fatty liver disease – a modern look at the problem. Lechaschii Vrach. 2010;5(5):57-61. (in Russian).

Hall AR, Dhillon AP, Green AC, et al. Hepatic steatosis estimated microscopically versus digital image analysis. Liver Int. 2013 Jul;33(6):926-35. doi: 10.1111/liv.12162.

Larter CZ, Chitturi S, Heydet D, Farell G. A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol. 2010 Apr;25(4):672-90. doi: 10.1111/j.1440-1746.2010.06253.x.

Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010 May;51(5):1820-32. doi: 10.1002/hep.23594.

European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004.

Ratziu V, Bellentani S, Cortes-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol. 2010 Aug;53(2):372-84. doi: 10.1016/j.jhep.2010.04.008.

Bellentani S, Saccoccio G, Masutti F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000 Jan 18;132(2):112-7.

 World Health Organization. Obesity and overweight. Available from: http://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight. Accessed: February 16, 2018.

Yan E, Durazo F, Tong M, Hong K. Nonalcoholic fatty liver disease: pathogenesis, identification, progression, and management. Nutr Rev. 2007 Aug;65(8 Pt 1):376-84.

Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x.

Lazo M, Clark J. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008 Nov;28(4):339-50. doi: 10.1055/s-0028-1091978.

Musso G, Gambino R, Cassader M. Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obes Rev. 2010 Jun;11(6):430-45. doi: 10.1111/j.1467-789X.2009.00657.x.

Younossi ZM, Stepanova M, Negro F, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore). 2012 Nov;91(6):319-27. doi: 10.1097/MD.0b013e3182779d49.

Barrera F, George J. The role of diet and nutritional intervention for the management of patient with NAFLD. Clin Liver Dis. 2014 Feb;18(1):91-112. doi: 10.1016/j.cld.2013.09.009.

Chiu S, Sievenpiper IL, de Souza RJ, et al. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr. 2014 Apr;68(4):416-23. doi: 10.1038/ejcn.2014.8.

Filippova AYu. Changes of direct markers of liver fibrosis in patients with steatohepatitis nonalcoholic and alcoholic genesis on the background of obesity and pathology of the biliary tract. Zaporozskij medicinskij zurnal. 2017;(101):168-171. doi: 10.14739/2310-1210.2017.2.95682. (in Ukrainian).

Didenko VI. Modern methods for determining liver fibrosis. Gastroenterologìa. 2013;(48):28-35. doi: 10.22141/2308-2097.2.48.2013.86150. (in Russian).

Bobronnikova LR, Belovol AN. The metabolic effects and the influence of adipocikines in patients with associated clinical variants of nonalcoholic fatty liver disease and diabetes type 2. Evrazijskij souz ucenyh. 2016;(28-1):15-17. (in Russian).

Kodama Y, Brenner DA. c-Jun N-terminal kinase signaling in the pathogenesis of nonalcoholic fatty liver disease: Multiple roles in multiple steps. Hepatology. 2009 Jan;49(1):6-8. doi: 10.1002/hep.22710.

Park KG, Min AK, Koh EH, et al. Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Hepatology. 2008 Nov;48(5):1477-86. doi: 10.1002/hep.22496.

Aleman G, Torres N, Tovar AR. Peroxisome proliferator-activated receptors (PPARs) in obesity and insulin resistance development. Rev Invest Clin. 2004 May-Jun;56(3):351-67. (in Spanish).

Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002 May 31;296(5573):1655-7. doi: 10.1126/science.296.5573.1655.

Kosobyan EP, Smyrnova OM. Current concepts of the pathogenesis of non-alcoholic fatty liver disease. Sakharni Diabet. 2010;(31):55-64. (in Russian).

Guenther B. Obesity and Free Fatty Acids (FFA). Endocrinol Metab Clin North Am. 2008 Sep;37(3):635-46, viii-ix. doi: 10.1016/j.ecl.2008.06.007.

Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016 Aug;65(8):1038-48. doi: 10.1016/j.metabol.2015.12.012.

Altinbas A, Sowa JP, Hasenberg T, Canbay A. The diagnosis and treatment of non-alcoholic fatty liver disease. Minerva Gastroenterol Dietol. 2015 Sep;61(3):159-69.

Topchieva LV, Kurbatova IV, Dudanova OP, Sokolovskaya AA, Shipovskaya AA. Gene polymorphism of proinflammatory cytokines (TNF, IL6) and their receptors (TNFRSF1A, TNFRSF1B, IL6R): implications for non-alcoholic fatty liver disease. Trudy Karelʹskogo naucnogo centra Rossijskoj akademii nauk. 2017;(5):3-22. doi: 10.17076/eb568. (in Russian).

Tyzhnenko TV, Gorshunska MJu, Cherniaieva AO, et al. Single-nucleotide polymorphism -308G/A tumor necrosis factor-α (TNF) gene in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease. Problemi endokrinnoi patologii. 2015;(4):44-52. (in Ukrainian).

Karachentsev Y, Gorshunska M, Kravchun N, et al. Association between +276 G>T polymorphism of the adiponectin gene (ADIPOQ) and insulin resistance in Ukrainian patients with type 2 diabetes mellitus (T2DM). Endocrine Abstracts. 2015;(37):EP346. doi: 10.1530/endoabs.37.EP346.

Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive monitoring of nonalcoholic steatohepatitis: present and future. Hepatology. 2007 Aug;46(2):582-9. doi: 10.1002/hep.21768.

Shvartz V. Adipose tissue inflammation. Part 1. Morphological and functional manifestations. Problemi Endocrinologii. 2009;55(4):44-9. (in Russian).

Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005 May;115(5):911-9; quiz 920. doi: 10.1016/j.jaci.2005.02.023.

Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE. Diabetes and apoptosis: lipotoxicity. Apoptosis. 2009 Dec;14(12):1484-95. doi: 10.1007/s10495-009-0352-8.

Clemente-Postigo M, Queipo-Ortuño MI, Fernandez-Garcia D, Gomez-Huelgas R, Tinahones FJ, Cardona F. Adipose tissue gene expression of factors related to lipid processing in obesity. PLoS One. 2011;6(9):e24783. doi: 10.1371/journal.pone.0024783.

Klop B, Jukema JW, Rabelink TJ, Castro Cabezas M. Physician’s guide for the management of hypertriglyceridemia: The etiology of hypertriglyceridemia determines treatment strategy. Panminerva Med. 2012 Jun;54(2):91-103.

Asrih M, Jornayvaz R. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance. J Endocrinol. 2013 Aug 28;218(3):R25-36. doi: 10.1530/JOE-13-0201.

Abiru S, Migita K, Maeda Y, et al. Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis. Liver Int. 2006 Feb;26(1):39-45. doi: 10.1111/j.1478-3231.2005.01191.x.

Myers MG, Cowley MA, Münzberg H. Mechanisms of leptin action and leptine resistance. Annu Rev Physiol. 2008;70:537-56. doi: 10.1146/annurev.physiol.70.113006.100707.

Skrypnyk NV. The role of resistin in the formation of diabetic steatohepatitis in patients with type 2 diabetes with metabolic syndrome. Clinical Endocrinology and Endocrine Surgery. 2007;3(20):61-63. (in Ukrainian).

Gorshuns'ka MJu, Karachencev JuI, Krasova NS, et al. Resistin levels in the circulation of type 2 diabetic patients: relation to the components of metabolic syndrome. Problemi endokrinnoi patologii. 2007;(1):5-14. (in Ukrainian).

Zemlianitsyna OV, Romanova IP, Cherniavskaya IV, Dunayeva IP, Kravchun NA. Relationship between serum resistin with clinical, metabolic and immunological parameters in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. Wschodnioeuropejskie czasopismo naukowe. 2016;(5):85-91. (in Russian).

Ogneva OV. Correlation of metabolic indices with plasma leptin level in patients with nonalcoholic fatty liver disease in combination with type 2 diabetes mellitus and obesity. Mìžnarodnij endokrinologìčnij žurnal. 2012;(43):15-7. (in Ukrainian).

Zhuravlyova LV, Lopina NA. Fractalkine level and its importance in forecasting presence and severity of coronary atherosclerosis. Ukrainian Cardiology Journal. 2016;(4):62-66. (in Russian).

Won JC, Park CY, Oh SW, Lee ES, Byung-Soo Y, Min-Seon K. Plasma clusterin (ApoJ) levels are associated with adіposіty and systemic inflammatіon. PLoS One. 2014 Jul 30;9(7):e103351. doi: 10.1371/journal.pone.0103351.

Wang XH, Dou LZ, Gu C, Wang XQ. Plasma levels of omentin-1 and visfatin in senile patients with coronary heart disease and heart failure. Asian Pac J Trop Med. 2014 Jan;7(1):55-62. doi: 10.1016/S1995-7645(13)60192-3.

Mm WQ, Fan J, Khor S, Song M, Hong W, Dai X. Serum vaspin levels and vaspin mRNA expressіon in subcutaneous adіpose tіssue in women with gestational diabetes mellitus. Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:98-101. doi: 10.1016/j.ejogrb.2014.09.008.

Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med. 2007 Jan;24(1):1-6. doi: 10.1111/j.1464-5491.2007.02025.x.

Kravchun NA, Dunaeva IP. Hyperhomocysteinemia, cardiovascular diseases and type 2 diabetes. Zdorov’ja Ukrai'ny. 2012;(4):52-53. (in Russian).

Targher G, Bertolini L, Rodella S, et al. Non-alcoholic fatty liver disease in independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients. Diabetologia. 2008 Mar;51(3):444-50. doi: 10.1007/s00125-007-0897-4.

Babak OIa. Reasons and metabolic consequences of non-alcoholic fatty liver disease. Modern Gastroenterology. 2010;(54):8-16. (in Russian).

Badal SS, Danesh FR. Strategies to reverse endothelial dysfunction in diabetic nephropathy. Kidney Int. 2012 Dec;82(11):1151-4. doi: 10.1038/ki.2012.306.

Cheng H, Wang H, Fan X, Paueksakon P, Harris RC. Improvement of endothelial nitric oxide synthase activity retards the progression of diabetic nephropathy in db/db mice. Kidney Int. 2012 Dec;82(11):1176-83. doi: 10.1038/ki.2012.248.

Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histological features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015 Aug;149(2):389-97.e10. doi: 10.1053/j.gastro.2015.04.043.

Ekstedt M, Hagström 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 May;61(5):1547-54. doi: 10.1002/hep.27368.

Stepanova M, Rafiq N, Makhlouf H, et al. Predictors of all-cause mortality and liver -related mortality in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci. 2013 Oct;58(10):3017-23. doi: 10.1007/s10620-013-2743-5.

Jung JY, Park SK, Ryoo J-H, et al. Effect of Non-alcoholic fatty liver disease on left ventricular diastolic function and geometry in Korean general population: NAFLD, left ventricular diastolic dysfunction. Hepatol Res. 2017 May;47(6):522-532. doi: 10.1111/hepr.12770.

Seo SW, Gottesman RF, Clark JM, et al. Nonalcoholic fatty liver disease is associated with cognitive function in adults. Neurology. 2016 Mar 22;86(12):1136-42. doi: 10.1212/WNL.0000000000002498.

Celikbilek A, Celikbilek M, Bozkurt G. Cognitive assessment of patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2018 Aug;30(8):944-950. doi: 10.1097/MEG.0000000000001131.

Ichino N, Osakabe K, Nishikawa T, et al. A new index for non-invasive assessment of liver fibrosis. World J Gastroenterol. 2010 Oct 14;16(38):4809-16. doi: 10.3748/wjg.v16.i38.4809.

Ternovoy SK, Abdurakhmanov DT, Shiryaev GA. Diagnostic value of proton magnetic resonance spectroscopy of liver in the evaluation of treatment of steatosis and stetohepatitis. Kardiologicheskii vestnik. 2014;9(3):105-110. (in Russian).

Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007 Apr;45(4):846-54. doi: 10.1002/hep.21496.

Prosolenko KO, Kolesnikova OV. Non-invasive diagnosis of liver fibrosis in non-alcoholic fatty liver disease. Gostri ta nevidkladni stany u praktyci likarja. Zdorov’ja Ukrai'ny. 2009;(19):53-56. (in Ukrainian).

Bedel'baeva GG, Nurmakhanova ZhM, Erdash BE. Non-alcoholic fatty liver disease: markers of early diagnosis of fibrosis. Meditsina (Almaty). 2017;(183):99. (in Russian).

McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015 May;62(5):1148-55. doi: 10.1016/j.jhep.2014.11.034.

Brunt EM, Kleiner DE, Wilson L, Belt P, Neuschhwander-Tetri BA; NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meaning. Hepatology. 2011 Mar;53(3):810-20. doi: 10.1002/hep.24127.

Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 2007 Oct;47(4):598-607. doi: 10.1016/j.jhep.2007.07.006.

Pentjuk NO. Metabolic predictors of liver fibrosis in patients with chronic hepatitis. Experimental and Clinical Medicine. 2011;(50):134-138. (in Ukrainian).

Castéra L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005 Feb;128(2):343-50.

Sheptulina AF, Shirokova EN, Ivashkin VT. Non-invasive of liver fibrosis diagnostics: the role of serum markers. Rossijskij zurnal gastroenterologii, gepatologii, koloproktologii. 2015;25(2):28-40. (in Russian).

Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015 Apr;13(4):643-54.e1-9; quiz e39-40. doi: 10.1016/j.cgh.2014.04.014.

Feldstein AE, Wieckowska AЕ, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study steatohepatitis. Hepatology. 2009 Oct;50(4):1072-8. doi: 10.1002/hep.23050.

Kurbatova YV, Dudanova OP, Topchieva LV, Shipovskaia AA. Comparative analysis of biochemical and molecular genetic parameters of apoptosis in healthy donors and patients with non-alcoholic steatohepatitis (NASH) of different activity. Gastroenterologia Sankt-Peterburga. 2017;(1):87-87a. (in Russian).

Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A. Plasma transforming growth factor-betal level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther. 2001 Oct;15(10):1667-72.

Shipovskaya AA, Larina NA, Kurbatova IV, Dudanova OP. Clinical features of non-alcoholic fatty liver disease associated with type 2 diabetes. Journal of Biomedical Technologies. 2016;(1):41-47. (in Russian).

Hvorostinka VM, Vlasenko AV. The influence of fatty liver dystrophy in combination with metabolic syndrome on the peculiarities of diabetes mellitus. Mìžnarodnij endokrinologìčnij žurnal. 2007;(11):65-70. (in Ukrainian).

Kravchun NO, Zemlyanitsyna OV, Dorosh OG, Chernyavskaya IV. A differentiated approach to the treatment of nonalcoholic fatty liver disease in patients with type 2 diabetes. Clinical Endocrinology and Endocrine Surgery. 2013;2(43):47-55. (in Ukrainian).

Chalasani N, Younossi Z, Lavine JE, 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 Jun;55(6):2005-23. doi: 10.1002/hep.25762.

Pankiv VI. Diabetes mellitus type 2 and non-alcoholic fatty liver disease. The effects of metformin. Mìžnarodnij endokrinologìčnij žurnal. 2013;(53):55-63. doi: 10.22141/2224-0721.5.53.2013.84493. (in Russian).

Dudanova OP, Shipovskaya AA, Larina NA, Kurbatova IV. Nuclear receptor agonists in the treatment of non-alcoholic fatty liver disease. Gastroenterologia Sankt-Peterburga. 2017;(1):77-78. (in Russian).

Ratziu V, de Ledinghen V, Oberti F, et al. A randomized controlled trial of high-dose Ursodeoxycholic acid for non-alcoholic steatohepatitis. J Hepatol. 2011 May;54(5):1011-9. doi: 10.1016/j.jhep.2010.08.030.

Kurbatova IV, Dudanova OP, Shipovskaya AA. Features of changes in blood biochemical parameters in patients with non-alcoholic steatohepatitis during therapy with ursodeoxycholic acid. Prioritetnye nauchnye napravleniia: ot teorii k praktike. 2016;(22):35-40. (in Russian).

Urbanovych AM. Non-alcoholic steatohepatitis in patients with type 2 diabetes: a modern view of the problem. Mìžnarodnij endokrinologìčnij žurnal. 2009;(20):38-42. (in Ukrainian).

Kolesnikova EV. Non-alcoholic fatty liver disease and diabetes mellitus: possible risks, developmental mechanisms and methods of correction. Zdorov’ja Ukrai'ny. 2010;(1):42. (in Russian).

Mayevskaya MV, Morozova MA. Options of dyslipidemia treatment at non-alcoholic fatty liver disease. Rossijskij zurnal gastroenterologii, gepatologii, koloproktologii. 2016;26(4):55-61. (in Russian).

Hayashizaki-Someya Y, Kurosaki E, Takasu T, et al. Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient I-amino acid-defined diet in rats. Eur J Pharmacol. 2015 May 5;754:19-24. doi: 10.1016/j.ejphar.2015.02.009.

Koutsovasilis A. Effectiveness of dapagliflozin in nonalcoholic fatty liver disease in type 2 diabetes patients compared to sitagliptin and pioglitazone. Available from: https://www.easd.org/virtualmeeting/home.html#!resources/effectiveness-of-dapagliflozin-in-nonalcoholic-fatty-liver-disease-in-type-2-diabetes-patients-compared-to-sitagliptin-and-pioglitazone-1a7b221c-047b-4b67-8fa3-0abaa554da5e. Accessed: September 12, 2017.

Tobita H, Sato S, Miyake T, Ishihara S, Kinoshita Y. Effects of Dapagliflozin on Body Composition and Liver Tests in Patients with Nonalcoholic Steatohepatitis Associated with Type 2 Diabetes Mellitus: A Prospective, Open-label, Uncontrolled Study. Curr Ther Res Clin Exp. 2017 Jul 8;87:13-19. doi: 10.1016/j.curtheres.2017.07.002.

Zhurakovsky IP, Arkhypov SA, Pustovetova MG, Kunts TA, Bitkhaeva MV, Marinkin IO. Antifibrotic effect of melatonin during the combine dystrophic and degenerative pathology development in local chronic inflammatory process. Sibirskoe medicinskoe obozrenie. 2011;(69):30-33. (in Russian).

Michurina SV, Vasendin DV, Ishchenko IYu. Structural-functional changes in the liver of Vistar rats with experimental obesity and correction of melatonin. Izvestia Tulʹskogo gosudarstvennogo universiteta. Estestvennye nauki. 2014;1(1):291-299. (in Russian).

Zemlianitsyna O, Polozova L, Karachentsev YuI, Sinaiko V, Kravchun N. Features of excretion of melatonin in urine in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease with manifestations of fibrosis and its relationship with certain metabolic and immunological indicators. Georgian medical news. 2018;(274):103-107.

Wexler R, Pleister A, Raman SV, Borchers JR. Therapeutic lifestyle changes for cardiovascular disease. Phys Sportsmed. 2012 Feb;40(1):109-15. doi: 10.3810/psm.2012.02.1957.

Dunajeva IP. Adyponektynemija ta asocijovani faktory kardiovaskuljarnogo ryzyku u hvoryh na cukrovyj diabet 2 typu z nealkogol'noju zhyrovoju hvoroboju pechinky ta i'h nutrijentna korekcija. Diss. kand. med. nauk [Adiponectinemia and associated cardiovascular risk factors in patients with type 2 diabetes with non-alcoholic fatty liver disease and their nutritional correction. PhD diss.]. Кyiv; 2017. 26 p. (in Ukrainian).




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