Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Obesity Reports
Published in: Current Obesity Reports 3/2019

01-09-2019 | Obesity | Obesity Treatment (CM Apovian, Section Editor)

Nonalcoholic Fatty Liver Disease and Obesity Treatment

Authors: Katherine T. Brunner, Cameron J. Henneberg, Robert M. Wilechansky, Michelle T. Long

Published in: Current Obesity Reports | Issue 3/2019

Login to get access

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.
Literature
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
3.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
8.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRef
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.CrossRefPubMedPubMedCentral
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.CrossRef
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.CrossRef
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRef
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
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
39.
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.CrossRefPubMedPubMedCentral
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.CrossRef
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.CrossRef
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.CrossRef
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
59.
Kargiotis K. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome. World J Gastroenterol. 2015;21:7860.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
61.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
Metadata
Title
Nonalcoholic Fatty Liver Disease and Obesity Treatment
Authors
Katherine T. Brunner
Cameron J. Henneberg
Robert M. Wilechansky
Michelle T. Long
Publication date
01-09-2019
Publisher
Springer US
Published in
Current Obesity Reports / Issue 3/2019
Electronic ISSN: 2162-4968
DOI
https://doi.org/10.1007/s13679-019-00345-1

Other articles of this Issue 3/2019

Current Obesity Reports 3/2019 Go to the issue

Obesity Treatment (CM Apovian, Section Editor)

Ethnic Disparities in Adiposity: Focus on Non-alcoholic Fatty Liver Disease, Visceral, and Generalized Obesity

Obesity Treatment (CM Apovian, Section Editor)

Mechanism of Glucagon-Like Peptide 1 Improvements in Type 2 Diabetes Mellitus and Obesity

Obesity Treatment (CM Apovian, Section Editor)

FSP27 and Links to Obesity and Diabetes Mellitus

Metabolism (M Dalamaga, Section Editor)

Oxytocin and Vasopressin Systems in Obesity and Metabolic Health: Mechanisms and Perspectives

Health Services and Programs (R Welbourn and CM Borg, Section Editors)

How Group-Based Interventions Can Improve Services for People with Severe Obesity

Obesity Treatment (CM Apovian, Section Editor)

Gut Microbiota Dysbiosis in Human Obesity: Impact of Bariatric Surgery
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits