Treatment of non-alcoholic fatty liver disease

Authors

  • Susana Gutt Italian Hospital, Autonomous City of Buenos Aires, Argentina
  • María Álvarez Center for the Study and Treatment of Severe Obesity-CETOS, Autonomous City of Buenos Aires, Argentina
  • María Yuma Italian Hospital, Autonomous City of Buenos Aires, Argentina
  • Marianela Aguirre Ackermann Comprehensive Center of Endocrinology and Nutrition (CIEN), Corrientes, Argentina
  • María Coronel "Maffei" Medical Center, Autonomous City of Buenos Aires, Argentina
  • Carla Gauna "José de San Martin" Clinical Hospital, Autonomous City of Buenos Aires, Argentina
  • Sandra González IMA Clinic, Adrogué, Province of Buenos Aires, Argentina
  • Paula Lifszyc "Carlos Durand" Hospital, Autonomous City of Buenos Aires, Argentina
  • Estrella Menéndez "Norberto Quirno" Center for Medical Education and Clinical Research (CEMIC); Argentine Diabetes Society, Autonomous City of Buenos Aires, Argentina
  • Juliana Mociulsky Buenos Aires ICBA Cardiovascular Institute, Autonomous City of Buenos Aires, Argentina
  • Carla Musso Favaloro Foundation; "César Milstein" Assistance Unit- PAMI, Autonomous City of Buenos Aires, Argentina
  • Paola Polo Las Lomas Sanatorium; Hospital "San José", Campana, Province of Buenos Aires, Argentina
  • María Victoria Salinas CEMIC, Autonomous City of Buenos Aires, Argentina
  • Guadalupe Vanoli José María Ramos Mejía General Acute Hospital, Autonomous City of Buenos Aires, Argentina
  • Susana Fuentes "El Cruce" Hospital, Province of Buenos Aires, Argentina

DOI:

https://doi.org/10.47196/diab.v52i1.80

Keywords:

non alcoholic fatty liver disease, steatosis, diabetes and fatty liver, fatty liver pharmacotherapy, bariatric surgery and fatty liver

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a fatty disease of the liver that is not associated with alcohol. Its prevalence increases along with the epidemic of obesity and type 2 diabetes, and the risk of suffering a more aggressive liver disease is greater with the consequent increase in cirrhosis, hepatocellular carcinoma and cardiovascular disease (CVD). The ectopic accumulation of fat is associated with high-fat diets and high energy density, hyperglycemia and insulin resistance that lead to the suppression of hepatic glucose production and decreased glucose uptake by the skeletal muscle which promotes the lipogenesis of novo and generates a vicious circle that favors even more steatosis.

Author Biographies

Susana Gutt, Italian Hospital, Autonomous City of Buenos Aires, Argentina

Medical Specialist in Nutrition

María Yuma, Italian Hospital, Autonomous City of Buenos Aires, Argentina

Medical specialist in Nutrition

Marianela Aguirre Ackermann, Comprehensive Center of Endocrinology and Nutrition (CIEN), Corrientes, Argentina

Medical specialist in Internal Medicine and Nutrition

Carla Gauna, "José de San Martin" Clinical Hospital, Autonomous City of Buenos Aires, Argentina

Physician specialist in Nutrition

Sandra González, IMA Clinic, Adrogué, Province of Buenos Aires, Argentina

Medical Clinic specialized in Diabetes

Paula Lifszyc, "Carlos Durand" Hospital, Autonomous City of Buenos Aires, Argentina

Nutritionist; Plant Physician of the Nutrition Unit

Estrella Menéndez, "Norberto Quirno" Center for Medical Education and Clinical Research (CEMIC); Argentine Diabetes Society, Autonomous City of Buenos Aires, Argentina

Medical specialist in Nutrition, specialized in Diabetes, Nutrition and Diabetes Service of the "Norberto Quirno" Center for Medical Education and Clinical Research (CEMIC); Former director of the Graduate School of Diabetes (Argentine Diabetes Society)

Juliana Mociulsky, Buenos Aires ICBA Cardiovascular Institute, Autonomous City of Buenos Aires, Argentina

Endocrinologist, Head of the Nutrition Unit, Buenos Aires Cardiovascular Institute

Carla Musso, Favaloro Foundation; "César Milstein" Assistance Unit- PAMI, Autonomous City of Buenos Aires, Argentina

Endocrinologist; Diabetes Coordinator

Paola Polo, Las Lomas Sanatorium; Hospital "San José", Campana, Province of Buenos Aires, Argentina

Endocrinologist

María Victoria Salinas, CEMIC, Autonomous City of Buenos Aires, Argentina

Medical specialist in Clinic and Nutrition

Guadalupe Vanoli, José María Ramos Mejía General Acute Hospital, Autonomous City of Buenos Aires, Argentina

Medical specialist in Nutrition; Staff Physician of the Nutrition and Diabetes Unit of the José María Ramos Mejía General Acute Hospital

Susana Fuentes, "El Cruce" Hospital, Province of Buenos Aires, Argentina

Medical specialist in Internal Medicine; Doctor at "El Cruce" Hospital, Comprehensive Medical Care Service for the Community

References

Quintero F, Botero V, D’Agostino D et al. Enfermedad del hígado graso no alcohólico (EHGNA): revisión y puesta al día. Grupo de Trabajo de la Sociedad Latinoamericana de Gastroenterología Hepatología y Nutrición Pediátrica (SLAGHNP) Acta Gastroenterol Latinoam 2016; 46: 246-264.

Bril F, Cusi K. Nonalcoholic fatty liver disease. The new complication of type 2 diabetes mellitus. Endocrinol Metab Clin N Am 2016; 45:765-781.

Della-Corte C, Mazzotta A, Nobili V. Enfermedad del hígado graso y obesidad en pacientes jóvenes. Curr Opin Endocrinol Diabetes and Obes 2016; 23:66-71.

Vernon G, Baranova A, Younossi Z. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non- alcoholic steaohepatitis in adults Alim Pharamacol Ther 2011; 34: 274-285.

Younossi Z, Koening A, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver dieases. Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64 (1): 73-84.

Anderson P, Gual A, Colon J. Alcohol y atención primaria de la salud: informaciones clínicas básicas para la identificación y el manejo de riesgos y problemas. Washington, D.C.: OPS, © 2008 ISBN 978 92 75 32856 9.

Cusi K. Treatment of patients with type 2 diabetes and non-alcoholic fatty liver disease: current approaches and future directions. Diabetología 2016; 59: 1112-1120.

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO). Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetología 2016; 59: 1121-1140.

Kleiner D, Brunt E, Van Natta M, et al. Design and validation of a histoligical scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41:1313-1321.

Mottin C, Moretto M, Padoin AV, et al. Histological behavior of hepatic steatosis in morbidly obese patients weight loss induced by bariatric surgery. Obesity Surgery 2005; 15 (6): 788-793.

Buchwald H, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004; 292:1724-1737.

Hannah WN Jr, Harrison S. Effect of weight loss, diet, exercise and bariatric surgery on nonalcoholic fatty . Clin Liver Disease 2016; Vol 20 (2): 339-350.

Milic S, Mikolasevic I, Krznaric I, et al. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options. Drug Design, Development and Therapy 2015; 9: 4835-4845.

Baran B, Akyüz F. Non-alcoholic fatty liver disease: What has changed in the treatment since the beginning? World J Gastroenterol 2014; 20(39): 14219-14229.

Musso G, Cassader M, Rosina F, et al. Impact of treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta analysis of randomised trials. Diabetologia 2012; 55: 885-9.

Abidin-Ozturk Z, Kadayifci A. Insulin sensitizers for the treatment of non-alcoholic fatty liver disease . World J Hepatol 2014; 6 (4): 199-206.

Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of nonalcoholic 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):2005-2023.

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: 372-384.

Zheng J, Woo S, Hu X, et al. Metformin and metabolic diseases: a focus on hepatic aspects. Front Med 2015; 9(2): 173-186.

Cusi K, Yau H, Rivera K, Lomonaco R. The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr Diab Rep (2013) 13:329-341.

Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355:2297-307.

Boettcher E, Csako G, Pucino F, et al. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Alimentary Pharmacology & Therapeutics 2012; 35 (1): 66-75.

Klein T, Mark M, Schuppan D, et al. The dipeptidyl peptidase 4 inhibitor linagliptin is an effective therapeutic for metabolic liver disease in several rodent models of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic. Hepatology 2011; 54 (4) Suppl: 36.

Hazlehurst J, Woods C, Marjot TH, et al. Non-alcoholic fatty liver disease and diabetes. Metabolism Clinical and Experimental 2016; 65: 1096-1108.

Ding X, Saxena N, Lin S, et al. Exendin-4, a GLP-1 receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 2006; 43: 173-81.

Verges B, Bouillet B, Guiu B, et al. Treatment with liraglutide leads to an important reduction in liver fat content, assessed by magnetic resonance spectroscopy in people with type 2 diabetes. Clinical Trial Registration Number: EudraCT: 2012-000375-16.

Treeprasertsuk S, Björnsson E, Enders F, et al. NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol 2013; 19 (8): 1219-1229.

Armstrong MJ, Gaunt P, Aithal G, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016; 387: 679-690.

Kern M, Klöting N, Niessen H, et al Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity. Plos one 2012; 7(6):e38744.

Klein T. Linagliptin alleviates hepatic steatosis and in ammation in a mouse model of nonalcoholic. Med Mol Morphol 2014; 47:137-149.

Iwasaki T, Yoneda M, Inamori M, et al. Sitagliptin as a novel treatment agent for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. Hepatogastroenterology 2011; 58:2103-2105.

Arase Y, Kawamura Y, Seko Y, et al. Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease. Hepatology 2013; 43:1163-1168.

Takayasu I, Yohei S, Tsuneiyuki M, et al The dipeptidyl peptidase-4 inhibitor teneligliptin attenuates hepatic lipogenesis via AMPK activation in non-alcoholic fatty liver disease model mice. Int J Mol Sci 2015; 16: 29207-29218.

Tahara A, Kurosaki E, Yokono M, et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 2013; 715:246-55.

Nakano S, Katsuno K, Isaji M, et al. Remogliflozin etabonate improves fatty liver disease in diet-induced obese male mice. J Clin Exp Hepatol 2015; 5 (3), 190-198.

Suzuki M, Takeda M, Kito A, et al. Tofogliflozin, a sodium/glucose cotransporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models. Nutr Diabetes 2014; 4 (7), e125.

Harrison SA, Fecht W, Brunt EM, et al. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hematology 2009; 49: 80-86.

Barb D, Portillo-Sánchez P, Cusi K. Pharmacological management of nonalcoholic fatty disease Metabolism Clinical and Experimental 2016; 65:1183-1195.

Assy N, Hussein O, Abassi Z. Weight loss induced by orlistat reverses fatty infiltration and improves hepatic fibrosis in obeses patients with non-alcoholic steatohepatitis. Gut 2007; 56: 443-444.

Younossi ZM, Reyes MJ, Mishra A, et al. Systematic review with meta-analysis: non-alcoholic steatohepatitis- a case for personalized treatment based on pathogenic targets. Aliment Pharmacy There 2014; 39: 3-1.

Rotman Y, Sanyal A Current and upcoming pharmacotherapy for non alcoholic fatty liver disease. Gut 2017; 66:180-190.

Mintziori G, Polyzos S. Emerging and future therapies for nonalcoholic steatohepatitis in adults. Expert Opinion on Pharmacotherapy 2016; 17:1937-1946.

Sanyal A, Chalasani N, Kowkley K, et al. Pioglitazone, vitamin E or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010; 362:1675-1685.

Lavine J, Schwimmer J, Van Natta M, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescent: the TONIC randomized controlled trial. JAMA 2011;305:1659-1668.

Miller E, Pastor-Barriuso R, Dalal D, et al. Meta analysis high dosage vitamin E supplementation may increase all cause mortality. Ann Intern Med 2005; 142:37-46.

Rotman Y, Sanyal A. Current and upcoming pharmacotherapy for non alcoholic fatty liver disease. Gut 2017; 66:180-190.

Zein C, Lopez R, Fu X, et al. Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. Hepatology 2012; 56:1291-1299.

Zein C, Yerian L, Gogate P, et al. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology 2011; 54:1610-1619.

Eslami L, Merat S, Malekzadeh R, et al. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database of Systematic Reviews 2013; Issue 12. Art. No.: CD008623.

Takahashi Y, Sugimoto K, Inui H, et al. Current pharmacological therapies for nonalcoholic fatty liver disease /nonalcoholic steatohepatitis. World J Gastroenterol 2015; 21 (13): 3777-3785.

Hafeez S, Ahmed M. Review article bariatric surgery as potential treatment for nonalcoholic fatty liver disease: a future treatment by choice or by chance? J Obes 2013; Article ID 839275.

Chávez-Tapia NC, Tellez-Avila FI, Barrientos-Gutiérrez T. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev 2010; (1):CD007340.

Chalasani N, Younossi Z, Lavine JE, et al. American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterology. The diagnosis and management of nonalcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142:1592-1609.

Bril F, Cusi K. Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action. Diabetes Care 2017; 40:419-430.

Taitano A, Markow M, Finan JE, et al. Bariatric surgery improves histological features of nonalcoholic fatty liver disease and liver fibrosis. J Gastrointest Surg 2015; 19:429-437.

Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of non-alcoholic steatohepatitis in morbidly obese patients. Gastroenterology 2015; 149:379-388.

Goossens N, Hoshida Y, Min Song W, et al. Nonalcoholic steatohepatitis is associated with increased mortality in obese patients undergoing bariatric surgery. Clinical Gastroenterology and Hepatology 2016; 14:1619-1628.

Mummadi R, Kasturi K, Chennareddygari S, Sood G. Effect of bariatric surgery on non-alcoholic fatty liver disease: systematic review and meta-analysis. Clinical Gastroenterology and Hepatology 2008; 1396-1402.

Klebanoff M, Corey K, Chhatwal J, et al. Bariatric surgery for non-alcoholic steatohepatitis: a clinical and cost-effectiveness analysis. Hepatology Online 27/2/2017; doi: 10.1002/hep.28958.

Mathurin P, Hollebecque A, Arnalsteen L, et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 2009; 137:532-540.

Mosko JD, Nguyen GC. Increased perioperative mortality following bariatric surgery among patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9:897-901.

Shimizu H, Phuong V, Maia M, Kroh M, Chand B, Schauer PR, Brethauer SA. Bariatric surgery in patient swith liver cirrosis. Surgery for Obesity and Related Diseases 2013; 9: 1-6.

Grimm IS, Schindler W, Haluszka O. Steatohepatitis and fatal hepatic failure after biliopancreatic diversion. Am J Gastroenterol 1992; 87:775-779.

Published

2023-01-10

How to Cite

Gutt, S., Álvarez, M., Yuma, M., Aguirre Ackermann, M., Coronel, M., Gauna, C., González, S., Lifszyc, P., Menéndez, E., Mociulsky, J., Musso, C., Polo, P., Salinas, M. V., Vanoli, G., & Fuentes, S. (2023). Treatment of non-alcoholic fatty liver disease. Journal of the Argentine Society of Diabetes, 52(1 (2018), 10–24. https://doi.org/10.47196/diab.v52i1.80