DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20205134

Potential targets for prevention and treatment of non-alcoholic fatty liver disease in adults

Jarnail S. Braich

Abstract


Non-alcoholic fatty liver disease (NAFLD) is a common condition worldwide contributing to serious liver disorders like hepatic fibrosis and hepatocellular carcinoma. Most common of NAFLD etiology is a sedentary lifestyle and taking a high-calorie diet. Presently there is no drug available for the treatment of NAFLD and only dietary measures, increased physical activity and exercise, antioxidants are the options. In this review, detailed pathophysiology, diagnostic methods and potential targets for prevention and timely treatment of NAFLD have been described.


Keywords


Non-alcoholic fatty liver disease, Non-Alcoholic Steatohepatitis, Antioxidants, Hypolipidemic drugs, Insulin resistance, Insulin sensitizers

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References


Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15 (1):11-20.

Chalasani N, Younossi Z, Lavine JE, Diehl AM, Blunt EM, Cusi K, 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.

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of non-alcoholic fatty liver disease-Metanalytic assessment of prevalence, incidence and outcomes. Hepatol. 2016;64(1):73-84.

Hallsworth K, Adams LA. Lifestyle modification in NAFLD//NASH: facts and figures. JHEP Rep. 2019; 1(6):468-79.

Adams LA, Feldstein AE. Non-invasive diagnosis of non-alcoholic fatty liver and non-alcoholic steatohepatitis. J Dig Dis. 2011;12(1):10-6.

Shen FF, Li LG. Advances in noninvasive methods diagnosing nonalcoholic liver disease. J Dig Dis. 2016;17(9):565-71.

Wieckowska A, McCullough AJ, Feldstein AE. Non-invasive diagnosis and monitoring of non-alcoholic steatohepatitis: Present and future. Hepatol. 2007;46 (2):582-9.

Carter-Kent C, Zein NN, Feldstein AE. Cytokines in the pathogenesis of fatty liver and disease progression to steatohepatitis: implications for treatment. Am J Gastroenterol. 2008;103(4):1036-42.

Geroldi D, Falcone C, Emanuele E. Soluble receptors for advanced glycation end products from disease marker to potential therapeutic target. Curr Med Chem. 2006;13(17):1971-78.

Mikolasevic I, Milic S, Turk WT, Grgic I, Jakopcic I, Stimac D, Wensveen F, et al. Nonalcoholic fatty liver disease- A multisystem disease?. World J Gastroenterol. 2016;22(43):9488-505.

Adams LA, Angulo P. Treatment of non-alcoholic fatty liver disease. Postgrad Med J. 2006;82(967): 315-22.

Machado MV, Cortez-Pinto H. Non-alcoholic fatty liver disease: What the clinician needs to know. World J Gastroenterol. 2014;20(36):12956-80.

Moscatiello S, Di Luzio R, Bugianesi E, Suppini A, Hickman IJ, Di Domizio S, et al. Cognitive-behavioral treatment of non-alcoholic fatty liver disease: a propensity score-adjusted observational study. Obesity. 2011;19(4):763-70.

Takahashi H, Kotani K, Tanaka K, Egucih Y, Anzai K, et al. Therapeutic approaches to non-alcoholic fatty liver disease: exercise intervention and related mechanisms. Front Endocrinol. 2018;9:588.

Zelber-Sagi Salomone F, Mlynarksky L. The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: Evidence and plausible mechanisms. Liver Int. 2017;37:936-49.

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). EAS-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388-402.

Dunn W, Sanyal AJ, Brunt EM, Unalp-Arida A, Donohue M, McCullough AJ, et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease. J Hepatol. 2012;57(2):384-91.

Kwon HK, Greenson JK, Conjeevaram HS. Effect of lifetime alcohol consumption on the histological severity of non-alcoholic fatty liver disease. Liver Int. 2014;34:129-35.

Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and non-alcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatol. 2009;49(1):306-17.

Mazza A, Fruci B, Garinis GA, Giuliano S, Malaguarnera R, Belfiore A. The role of metformin in the management of NAFLD. Exp Diabetes Res. 2012;2012:716404.

Lin HZ, Yang SQ, Chuckaree C, Kuhajda F, Ronnet G, Diehl AM. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med. 2000;6(9):998-1003.

Zhang X, Harmsen WS, Mettler TA Kim WR, Roberts RO, Therneau TM, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatol. 2014;60(6):2008-16.

Loomba R. Rationale for conducting a randomised trial to examine the efficacy of metformin in improving survival in cirrhosis: Pleiotropic effects hypothesis. Hepatol. 2014;60(6):1818-22.

Tacelli M, Celsa C, Magro B, Giannetti A, Pennisi G, Spatola F, et al. Antidiabetic drugs in NAFLD: the accomplishment of two goals at once?. Pharmaceuticals. 2018;11:121.

Cooney RV, Harwood PJ, Franke AA, Narala K, Sundström AK, Berggren PO, et al. Products of gamma-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells. Free Radic Biol Med. 1995;19:259-69.

Christen S, Jiang Q, Shigenaga MK, Ames BN. Analysis of plasma tocopherols α, γ, and 5-nitro-γ in rats with inflammation by HPLC coulometric detection. J Lipid Res. 2002;43:1978-85.

Berbee M, Fu Q, Boerma M, Wang J, Kumar KS, Hauer-Jensen M. Gamma-tocotrienol ameliorates intestinal radiation injury and reduces vascular oxidative stress after total-body irradiation by an HMG-CoA reductase-dependent mechanism. Radiat Res. 2009;171:596-605.

Hadi HE, Vettor R, Rossato M. Vitamin E as a treatment for nonalcoholic fatty liver disease: reality or myth?. Antioxidants. 2018;7:12.

Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46.

Schurks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: Meta-analysis of randomiszed controlled trials. BMJ. 2010;341:c5702.

Klein EA, Thompson IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, et al. Vitamin E and the risk of prostate cancer: the selenium and vitamin E cancer prevention trial (SELECT). JAMA. 2011;306:1549-56.

Zelber-Sagi S, Salomone F, Webb M, Lotan R, Yeshua H, Halpern Z, et al. Coffee consumption and non-alcoholic fatty liver onset: a prospective study in the general population. Transl Res. 2015;165:428-36.

Johnson S, Renwei WK, Govindarajan S, Yu MC, Yuan JM. Coffee consumption and reduced risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study. Cancer Causes Control. 2011;22:503-10.

Chen S, Teoh NC, Chitturi S, Farrell GC. Coffee and non-alcoholic liver disease: brewing evidence from hepatoprotection. J Gastroenterol Hepatol. 2014;29 (3):435-41.

Perdomo CM, Fruhbeck G, Escalada J. Impact of nutritional changes on non-alcoholic fatty liver disease. Nutrtients. 2019;11:677.

Neuschwander-Teri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385(9972):956-65.

Tang JT, Mao YM. Development of new drugs for the treatment of non-alcoholic steatohepatitis. J Dig Dis. 2020;21:3-11.

Kashyap ML, Ganji S, Nakra NK, Kamanna VS. Niacin for treatment of non-alcoholic fatty liver disease (NAFLD): novel use for an old drug? J Clin Lipidol. 2019;13(6):873-79.

Martinez-Fernandez L, Laiglesia LM, Huerta AE, Martínez JA, Moreno-Aliaga MJ. Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome. Prostaglandins Other Lipid Mediat. 2015;121(Part A):24-41.

Yang J, Fernandez-Galilea M, Martinez-Fernandez L, González-Muniesa P, Pérez-Chávez A, Martínez JA, et al. Oxidative stress and non-alcoholic fatty liver disease: effects of omega-3 fatty acid supplementation. Nutrients. 2019;11(4):872.

Shiffman M, Freilich B, Vuppalanchi R, Watt K, Chan JL, Spada A, et al. Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3/7 activation in subjects with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2019;49(1):64-73.

Machado M V, Cortez-Pinto H. Gut microbiota and non-alcoholic fatty liver disease. Ann Heptatol. 2012;11(4):440-9.

Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet JP, et al. Towards the human intestinal microbiota phylogenetic core. Env Microbiol. 2009;11(10):2574-84.

Xie C, Halegoua-DeMarzio D. Role of probiotics in non-alcoholic fatty liver disease: does gut microbiota matter?. Nutrients. 2019;11(11):2837.

Chen YM, Liu Y, Zhou RF, Chen XL, Wang C, Tan XY, et al. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults. Sci Rep. 2016;6:19076.

Buchman AL, Dubin MD, Moukarzel AA, Jenden DJ, Roch M, Rice KM, et al. Choline deficiency: A cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatol. 1995;22(5):1399-403.

Sangouni AA, Ghavamzadeh S. A review of synbiotic efficacy in non-alcoholic fatty liver disease as a therapeutic approach. Diabetes Metab Syndr. 2019;13(5):2917-22.

Sharpton SR, Maraj B, Harding-Theobald E, Vittinghoff E, Terrault NA. Gut microbiome–targeted therapies in non-alcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. Am J Clin Nutr. 2019;110(1):139-49.

Foster T, Budoff MJ, Saab S, Ahmadi N, Gordon C, Guerci AD. Atorvastatin and antioxidants for the treatment of non-alcoholic fatty liver disease: The St Francis Heart Study randomised clinical trial. Am J Gastroenterol. 2011;106(1):71-7.