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Nonalcoholic Fatty Liver Disease and Obesity Treatment

  • Obesity Treatment (CM Apovian, Section Editor)
  • Published:
Current Obesity Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Nonalcoholic fatty liver disease (NAFLD), the most prevalent cause of chronic liver disease worldwide, is strongly associated with obesity and insulin resistance.

Recent Findings

Significant weight loss can improve NAFLD and nonalcoholic steatohepatitis (NASH). Diet and exercise that result in a sustained body weight reduction of 7–10% can improve liver fat content, NASH, and fibrosis. Vitamin E can be considered in patients with biopsy-proven NASH without diabetes, though caution must be used in those with prostate cancer. Pioglitazone improves liver histology, including fibrosis, and can be considered in patients with or without diabetes. Glucagon-like peptide-1 (GLP-1) antagonists may be beneficial in NASH, but more studies are needed before they can be recommended. Bariatric surgery, with resultant weight loss, can result in improvement in liver fat and inflammation.

Summary

NAFLD treatment includes diet and exercise with a target 7–10% weight reduction. Treatment goals include improvements in liver fat content, liver inflammation, and fibrosis.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

GLP-1:

Glucagon-like peptide-1

BMI:

Body mass index

MRI:

Magnetic resonance imaging

CT:

Computed tomography

MRS:

Magnetic resonance spectroscopy

MRE:

Magnetic resonance elastography

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

GGT:

Gamma-glutamyltransferase

NAS:

NAFLD activity score

PUFA:

Polyunsaturated fatty acids

IHTG:

Intrahepatic triglycerides

HIIT:

High-intensity interval training

SG:

Sleeve gastrectomy

RYGB:

Roux-en-Y gastric bypass

AGB:

Adjustable gastric banding

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.

    Article  PubMed  Google Scholar 

  2. Portillo-Sanchez P, Bril F, Maximos M, Lomonaco R, Biernacki D, Orsak B, et al. High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels. J Clin Endocrinol Metab. 2015;100:2231–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. Jama. 2015;313:2263–73.

    Article  CAS  PubMed  Google Scholar 

  4. Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, Castellanos M, Aller-de la Fuente R, Metwally M, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study. Gastroenterology. 2018;155:443–457.e17.

    Article  PubMed  Google Scholar 

  5. Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–397.e10.

    Article  PubMed  Google Scholar 

  6. Adams LA, Anstee QM, Tilg H, Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017;66:1138–53.

    Article  PubMed  Google Scholar 

  7. Patel NS, Doycheva I, Peterson MR, Hooker J, Kisselva T, Schnabl B, et al. Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2015;13:561–568.e1.

    Article  PubMed  Google Scholar 

  8. Foucher J. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut. 2006;55:403–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Huwart L, Sempoux C, Vicaut E, Salameh N, Annet L, Danse E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135:32–40.

    Article  PubMed  Google Scholar 

  10. Adams LA, George J, Bugianesi E, Rossi E, Boer WBD, van der Poorten D, et al. Complex non-invasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2011;26:1536–43.

    Article  CAS  PubMed  Google Scholar 

  11. Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–54.

    Article  CAS  PubMed  Google Scholar 

  12. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367–378.e5 quiz e14–15.

    Article  PubMed  Google Scholar 

  13. Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012;56:255–66.

    Article  PubMed  Google Scholar 

  14. Arendt BM, Comelli EM, Ma DWL, Lou W, Teterina A, Kim T, et al. Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n-3 and n-6 polyunsaturated fatty acids. Hepatology. 2015;61:1565–78.

    Article  CAS  PubMed  Google Scholar 

  15. Takeuchi Y, Yahagi N, Izumida Y, Nishi M, Kubota M, Teraoka Y, et al. Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit. J Biol Chem. 2010;285:11681–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Anania C, Perla FM, Olivero F, Pacifico L, Chiesa C. Mediterranean diet and nonalcoholic fatty liver disease. World J Gastroenterol. 2018;24:2083–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zelber-Sagi S, Salomone F, Mlynarsky 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.

    Article  CAS  PubMed  Google Scholar 

  18. Parker HM, Johnson NA, Burdon CA, Cohn JS, O’Connor HT, George J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;56:944–51.

    Article  CAS  PubMed  Google Scholar 

  19. Yan J-H, Guan B-J, Gao H-Y, Peng X-E. Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018;97:e12271.

    Article  CAS  Google Scholar 

  20. Argo CK, Patrie JT, Lackner C, Henry TD, de Lange EE, Weltman AL, et al. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J Hepatol. 2015;62:190–7.

    Article  CAS  PubMed  Google Scholar 

  21. Sanyal AJ, Abdelmalek MF, Suzuki A, Cummings OW, Chojkier M, EPE-A Study Group. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology. 2014;147:377–384.e1.

    Article  CAS  PubMed  Google Scholar 

  22. Scorletti E, Bhatia L, McCormick KG, Clough GF, Nash K, Hodson L, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the WELCOME* study. Hepatology. 2014;60:1211–21.

    Article  CAS  PubMed  Google Scholar 

  23. Ma J, Fox CS, Jacques PF, Speliotes EK, Hoffmann U, Smith CE, et al. Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. J Hepatol. 2015;63:462–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Abdelmalek MF, Suzuki A, Guy C, Unalp-Arida A, Colvin R, Johnson RJ, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatol Baltim Md. 2010;51:1961–71.

    Article  CAS  Google Scholar 

  25. Chiu S, Sievenpiper JL, de Souza RJ, Cozma AI, Mirrahimi A, Carleton AJ, 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;68:416–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Haufe S, Engeli S, Kast P, Böhnke J, Utz W, Haas V, et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatol Baltim Md. 2011;53:1504–14.

    Article  CAS  Google Scholar 

  27. Eckard C, Cole R, Lockwood J, Torres DM, Williams CD, Shaw JC, et al. Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial. Ther Adv Gastroenterol. 2013;6:249–59.

    Article  Google Scholar 

  28. Larsen TM, Dalskov S-M, van Baak M, Jebb SA, Papadaki A, Pfeiffer AFH, et al. Diets with high or low protein content and glycemic index for weight-loss maintenance. N Engl J Med. 2010;363:2102–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Markova M, Pivovarova O, Hornemann S, Sucher S, Frahnow T, Wegner K, et al. Isocaloric diets high in animal or plant protein reduce liver fat and inflammation in individuals with type 2 diabetes. Gastroenterology. 2017;152:571–585.e8.

    Article  CAS  PubMed  Google Scholar 

  30. Arslanow A, Teutsch M, Walle H, Grünhage F, Lammert F, Stokes CS. Short-term hypocaloric high-fiber and high-protein diet improves hepatic steatosis assessed by controlled attenuation parameter. Clin Transl Gastroenterol. 2016;7:e176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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. Obes Facts. 2016;9:65–90.

    Article  Google Scholar 

  32. Aller R, Izaola O, de la Fuente B, De Luis Román DA. Mediterranean diet is associated with liver histology in patients with non alcoholic fatty liver disease. Nutr Hosp. 2015;32:2518–24.

    PubMed  Google Scholar 

  33. Kontogianni MD, Tileli N, Margariti A, Georgoulis M, Deutsch M, Tiniakos D, et al. Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clin Nutrition. 2014;33:678–83.

    Article  CAS  Google Scholar 

  34. Ryan MC, Itsiopoulos C, Thodis T, Ward G, Trost N, Hofferberth S, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013;59:138–43.

    Article  CAS  PubMed  Google Scholar 

  35. • Misciagna G, Del Pilar DM, Caramia DV, Bonfiglio C, Franco I, Noviello MR, et al. Effect of a low glycemic index Mediterranean diet on non-alcoholic fatty liver disease. A randomized controlled clinici trial. J Nutr Health Aging. 2017;21:404–12 This randomized study showed that those randomized to the Mediterranean diet for 6 months had reduced hepatic steatosis on ultrasound compared with the control group.

    Article  CAS  PubMed  Google Scholar 

  36. Marchesini G, Petta S, Grave RD. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: pathophysiology, evidence, and practice. Hepatology. 2016;63:2032–43.

    Article  PubMed  Google Scholar 

  37. Guo R, Liong EC, So KF, Fung M-L, Tipoe GL. Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease. Hepatobiliary Pancreat Dis Int. 2015;14:139–44.

    Article  PubMed  Google Scholar 

  38. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328–57.

    Article  PubMed  Google Scholar 

  39. Exercise and NAFLD: is it worth the effort? - Schweitzer - 2017 - Hepatology - Wiley Online Library [Internet]. [cited 2019 Feb 7];Available from: https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.29356

  40. Zelber-Sagi S, Buch A, Yeshua H, Vaisman N, Webb M, Harari G, et al. Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial. World J Gastroenterol: WJG. 2014;20:4382–92.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hashida R, Kawaguchi T, Bekki M, Omoto M, Matsuse H, Nago T, et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: a systematic review. Hepatol. 2017;66:142–52.

    Article  Google Scholar 

  42. Keating SE, Hackett DA, Parker HM, Way KL, O’Connor HT, Sainsbury A, et al. Effect of resistance training on liver fat and visceral adiposity in adults with obesity: a randomized controlled trial. Hepatol Res Off J Jpn Soc Hepatol. 2017;47:622–31.

    Article  Google Scholar 

  43. Hallsworth K, Thoma C, Hollingsworth KG, Cassidy S, Anstee QM, Day CP, et al. Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial. Clin Sci. 2015;129:1097–105.

    Article  CAS  Google Scholar 

  44. Long MT, Pedley A, Massaro JM, Hoffmann U, Esliger DW, Vasan RS, et al. Hepatic steatosis is associated with lower levels of physical activity measured via accelerometry. Obes Silver Spring Md. 2015;23:1259–66.

    Article  Google Scholar 

  45. Oh S, Shida T, Yamagishi K, Tanaka K, So R, Tsujimoto T, et al. Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: a retrospective study. Hepatology. 2015;61:1205–15.

    Article  CAS  PubMed  Google Scholar 

  46. Keating SE, Hackett DA, Parker HM, O’Connor HT, Gerofi JA, Sainsbury A, et al. Effect of aerobic exercise training dose on liver fat and visceral adiposity. J Hepatol. 2015;63:174–82.

    Article  PubMed  Google Scholar 

  47. Zhang H-J, He J, Pan L-L, Ma Z-M, Han C-K, Chen C-S, et al. Effects of moderate and vigorous exercise on nonalcoholic fatty liver disease: a randomized clinical trial. JAMA Intern Med. 2016;176:1074–82.

    Article  PubMed  Google Scholar 

  48. • Sung K-C, Ryu S, Lee J-Y, Kim J-Y, Wild SH, Byrne CD. Effect of exercise on the development of new fatty liver and the resolution of existing fatty liver. J Hepatol. 2016;65:791–7 This large Korean-based observational study showed that even modest amounts of exercise, as examined over a 5-year follow-up period, were associated with improvement in and reduced incidence of NAFLD.

    Article  CAS  PubMed  Google Scholar 

  49. •• Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85 Landmark trial in nondiabetic patients showing that Vitamin E treatment improved NASH. Pioglitazone improved AST and ALT elevations, steatosis, and lobular inflammation, but not NASH.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Said A, Akhter A. Meta-analysis of randomized controlled trials of pharmacologic agents in non-alcoholic steatohepatitis. Ann Hepatol 2017;16:0–0.

  51. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases: hepatology, Vol. XX, no. X, 2017. Hepatology. 2018;67:328–57.

    Article  PubMed  Google Scholar 

  52. 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.

    Article  CAS  PubMed  Google Scholar 

  53. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cusi K, Orsak B, Bril F, Lomonaco R, Hecht J, Ortiz-Lopez C, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016;165:305–15.

    Article  PubMed  Google Scholar 

  55. Aghamohammadzadeh N, Niafar M, Dalir Abdolahinia E, Najafipour F, Mohamadzadeh Gharebaghi S, Adabi K, et al. The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients. Ther Adv Endocrinol Metab. 2015;6:56–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Erdmann E, Charbonnel B, Wilcox RG, Skene AM, Massi-Benedetti M, Yates J, et al. Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). Diabetes Care. 2007;30:2773–8.

    Article  CAS  PubMed  Google Scholar 

  57. • Feng W, Gao C, Bi Y, Wu M, Li P, Shen S, et al. Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease: 比较格列齐特、利拉鲁肽和二甲双胍对糖尿病合并非酒精性脂肪肝的影响的随机研究. J Diabetes. 2017;9:800–9 This randomized trial comparing several diabetes medications over 24 weeks show that those treated with liraglutide had the largest reduction in intrahepatic fat on ultrasound, compared with those treated with metformin or glicazide.

    Article  CAS  PubMed  Google Scholar 

  58. Simon TG, King LY, Zheng H, Chung RT. Statin use is associated with a reduced risk of fibrosis progression in chronic hepatitis C. J Hepatol. 2015;62:18–23.

    Article  CAS  PubMed  Google Scholar 

  59. Kargiotis K. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome. World J Gastroenterol. 2015;21:7860.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bril F, Portillo Sanchez P, Lomonaco R, Orsak B, Hecht J, Tio F, et al. Liver safety of statins in prediabetes or T2DM and nonalcoholic steatohepatitis: post hoc analysis of a randomized trial. J Clin Endocrinol Metab. 2017;102:2950–61.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Schwenger KJ. Clinical approaches to non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20:1712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Caiazzo R, Lassailly G, Leteurtre E, Baud G, Verkindt H, Raverdy V, et al. Roux-en-Y gastric bypass versus adjustable gastric banding to reduce nonalcoholic fatty liver disease: a 5-year controlled longitudinal study. Ann Surg. 2014;260:893–9.

    Article  PubMed  Google Scholar 

  63. Ruiz-Tovar J, Alsina ME, Alpera MR, OBELCHE Group. Improvement of nonalcoholic fatty liver disease in morbidly obese patients after sleeve gastrectomy: association of ultrasonographic findings with lipid profile and liver enzymes. Acta Chir Belg. 2017;117:363–9.

    Article  PubMed  Google Scholar 

  64. Kalinowski P, Paluszkiewicz R, Wróblewski T, Remiszewski P, Grodzicki M, Bartoszewicz Z, et al. Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass—results of a randomized clinical trial. Surg Obes Relat Dis. 2017;13:181–8.

    Article  PubMed  Google Scholar 

  65. Kalinowski P, Paluszkiewicz R, Ziarkiewicz-Wróblewska B, Wróblewski T, Remiszewski P, Grodzicki M, et al. Liver function in patients with nonalcoholic fatty liver disease randomized to Roux-en-Y gastric bypass versus sleeve gastrectomy: a secondary analysis of a randomized clinical trial. Ann Surg. 2017;266:738–45.

    Article  PubMed  Google Scholar 

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Correspondence to Michelle T. Long.

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Katherine T. Brunner declares that she has no conflict of interest.

Cameron J. Henneberg declares that he has no conflict of interest.

Robert M. Wilechansky declares that he has no conflict of interest.

Michelle T. Long has received research funding from Echosens Corporation.

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Brunner, K.T., Henneberg, C.J., Wilechansky, R.M. et al. Nonalcoholic Fatty Liver Disease and Obesity Treatment. Curr Obes Rep 8, 220–228 (2019). https://doi.org/10.1007/s13679-019-00345-1

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