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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 6/2016

01-06-2016 | Clinical Practice Guidelines

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

Authors: 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)

Published in: Diabetologia | Issue 6/2016

Login to get access

Excerpt

The Clinical Practice Guidelines propose recommendations for the diagnosis, treatment and follow-up of non-alcoholic fatty liver disease (NAFLD) patients and are the product of a joint effort by the 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). They update a position statement based on the 2009 EASL Special Conference [1]. …
Appendix
Available only for authorised users
Literature
1.
Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G (2010) A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 53:372–384PubMedCrossRef
2.
Guyatt GH, Oxman AD, Vist GE et al (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926PubMedPubMedCentralCrossRef
3.
Bellentani S, Saccoccio G, Masutti F et al (2000) Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132:112–117PubMedCrossRef
4.
Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:274–285PubMedCrossRef
5.
Younossi ZM, Stepanova M, Negro F et al (2012) Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 91:319–327CrossRef
6.
Fracanzani AL, Valenti L, Bugianesi E et al (2008) Risk of severe liver disease in NAFLD with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 48:792–798PubMedCrossRef
7.
Marchesini G, Mazzotti A (2015) NAFLD incidence and remission: only a matter of weight gain and weight loss? J Hepatol 62:15–17PubMedCrossRef
8.
Chalasani N, Younossi Z, Lavine JE et al (2012) 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 55:2005–2023PubMedCrossRef
9.
Barrera F, George J (2014) The role of diet and nutritional intervention for the management of patients with NAFLD. Clin Liver Dis 18:91–112PubMedCrossRef
10.
Chiu S, Sievenpiper JL, de Souza RJ et al (2014) 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 68:416–423PubMedPubMedCentralCrossRef
11.
Gerber L, Otgonsuren M, Mishra A et al (2012) Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study. Aliment Pharmacol Ther 36:772–781PubMedCrossRef
12.
Anstee QM, Targher G, Day CP (2013) Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 10:330–344PubMedCrossRef
13.
Valenti L, Al-Serri A, Daly AK et al (2010) Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 51:1209–1217PubMedCrossRef
14.
Liu YL, Patman GL, Leathart JB et al (2014) Carriage of the PNPLA3 rs738409 C > G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 61:75–81PubMedCrossRef
15.
Liu YL, Reeves HL, Burt AD et al (2014) TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat Commun 5:4309PubMedPubMedCentral
16.
Dongiovanni P, Petta S, Maglio C et al (2015) Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 61:506–514PubMedCrossRef
17.
Valenti L, Alisi A, Galmozzi E et al (2010) I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology 52:1274–1280PubMedCrossRef
18.
Nobili V, Donati B, Panera N et al (2014) A 4-polymorphism risk score predicts steatohepatitis in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 58:632–636PubMedCrossRef
19.
Ratziu V, Charlotte F, Heurtier A et al (2005) Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 128:1898–1906PubMedCrossRef
20.
Kleiner DE, Brunt EM (2012) Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis 32:3–13PubMedCrossRef
21.
Kleiner DE, Brunt EM, Van Natta M et al (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321PubMedCrossRef
22.
Bedossa P, Pathology Consortium FLIP (2014) Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 60:565–575PubMedCrossRef
23.
Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA, NASH Clinical Research Network (CRN) (2011) Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 53:810–820PubMedPubMedCentralCrossRef
24.
Ekstedt M, Hagstrom H, Nasr P et al (2015) Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 61:1547–1554PubMedCrossRef
25.
Brunt EM, Kleiner DE, Wilson LA et al (2009) Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 49:809–820PubMedPubMedCentralCrossRef
26.
Alkhouri N, De Vito R, Alisi A et al (2012) Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease. J Hepatol 57:1312–1318PubMedCrossRef
27.
Saadeh S, Younossi ZM, Remer EM et al (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123:745–750PubMedCrossRef
28.
Fishbein M, Castro F, Cheruku S et al (2005) Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J Clin Gastroenterol 39:619–625PubMedCrossRef
29.
Ryan CK, Johnson LA, Germin BI, Marcos A (2002) One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl 8:1114–1122PubMedCrossRef
30.
Fedchuk L, Nascimbeni F, Pais R et al (2014) Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther 40:1209–1222PubMedCrossRef
31.
Machado MV, Cortez-Pinto H (2013) Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol 58:1007–1019PubMedCrossRef
32.
European Association for the Study of the Liver, Asociacion Latinoamericana para el Estudio del Higado (2015) EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 63:237–264CrossRef
33.
Cusi K, Chang Z, Harrison S et al (2014) Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol 60:167–174PubMedCrossRef
34.
Kwok R, Tse YK, Wong GL et al (2014) Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther 39:254–269PubMedCrossRef
35.
Vuppalanchi R, Jain AK, Deppe R et al (2014) Relationship between changes in serum levels of keratin 18 and changes in liver histology in children and adults with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 12:2121–2130, e2121-2122PubMedPubMedCentralCrossRef
36.
Guha IN, Parkes J, Roderick P et al (2008) Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology 47:455–460PubMedCrossRef
37.
McPherson S, Anstee QM, Henderson E, Day CP, Burt AD (2013) Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels? Eur J Gastroenterol Hepatol 25:652–658PubMedCrossRef
38.
Wong VW, Vergniol J, Wong GL et al (2010) Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 51:454–462PubMedCrossRef
39.
Castera L, Foucher J, Bernard PH et al (2010) Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology 51:828–835PubMed
40.
Wong VW, Vergniol J, Wong GL et al (2012) Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 107:1862–1871PubMedCrossRef
41.
Petta S, Vanni E, Bugianesi E et al (2015) The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease. Liver Int 35:1566–1573PubMedCrossRef
42.
Vajro P, Lenta S, Socha P et al (2012) Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr 54:700–713PubMedCrossRef
43.
Nobili V, Svegliati-Baroni G, Alisi A, Miele L, Valenti L, Vajro P (2013) A 360-degree overview of paediatric NAFLD: recent insights. J Hepatol 58:1218–1229PubMedCrossRef
44.
Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A (2013) Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 5:1544–1560PubMedPubMedCentralCrossRef
45.
Alberti A, Vario A, Ferrari A, Pistis R (2005) Review article: chronic hepatitis C—natural history and cofactors. Aliment Pharmacol Ther 22(Suppl 2):74–78PubMedCrossRef
46.
Koliaki C, Szendroedi J, Kaul K et al (2015) Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab 21:739–746PubMedCrossRef
47.
Yki-Järvinen H (2014) Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2:901–910PubMedCrossRef
48.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef
49.
McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM (2015) Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol 62:1148–1155PubMedCrossRef
50.
Pais R, Charlotte F, Fedchuk L et al (2013) A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J Hepatol 59:550–556PubMedCrossRef
51.
Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S (2005) Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 42:44–52PubMedCrossRef
52.
Frith J, Day CP, Robinson L, Elliott C, Jones DE, Newton JL (2010) Potential strategies to improve uptake of exercise interventions in non-alcoholic fatty liver disease. J Hepatol 52:112–116PubMedCrossRef
53.
Caldwell SH, Crespo DM (2004) The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol 40:578–584PubMedCrossRef
54.
Aron-Wisnewsky J, Minville C, Tordjman J et al (2012) Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol 56:225–233PubMedCrossRef
55.
Gomez-Ambrosi J, Silva C, Galofre JC et al (2012) Body mass index classification misses subjects with increased cardiometabolic risk factors related to elevated adiposity. Int J Obes (Lond) 36:286–294CrossRef
56.
Chang Y, Ryu S, Suh BS, Yun KE, Kim CW, Cho SI (2012) Impact of BMI on the incidence of metabolic abnormalities in metabolically healthy men. Int J Obes (Lond) 36:1187–1194CrossRef
57.
Gomez-Ambrosi J, Catalan V, Rodriguez A et al (2014) Increased cardiometabolic risk factors and inflammation in adipose tissue in obese subjects classified as metabolically healthy. Diabetes Care 37:2813–2821PubMedCrossRef
58.
Ghouri N, Preiss D, Sattar N (2010) Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data. Hepatology 52:1156–1161PubMedCrossRef
59.
Gastaldelli A, Cusi K, Pettiti M et al (2007) Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology 133:496–506PubMedCrossRef
60.
Kotronen A, Juurinen L, Hakkarainen A et al (2008) Liver fat is increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects. Diabetes Care 31:165–169PubMedCrossRef
61.
Loomba R, Abraham M, Unalp A et al (2012) Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology 56:943–951PubMedPubMedCentralCrossRef
62.
Armstrong MJ, Adams LA, Canbay A, Syn WK (2014) Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 59:1174–1197PubMedCrossRef
63.
American Diabetes Association (2014) Standards of medical care in diabetes—2014. Diabetes Care 37(Suppl 1):S14–S80CrossRef
64.
Ortiz-Lopez C, Lomonaco R, Orsak B et al (2012) Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care 35:873–878PubMedPubMedCentralCrossRef
65.
Juurinen L, Tiikkainen M, Häkkinen AM, Hakkarainen A, Yki-Järvinen H (2007) Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab 292:E829–E835PubMedCrossRef
66.
Llaurado G, Sevastianova K, Sadevirta S et al (2015) Liver fat content and hepatic insulin sensitivity in overweight patients with type 1 diabetes. J Clin Endocrinol Metab 100:607–616PubMedCrossRef
67.
Anderwald C, Bernroider E, Krssak M et al (2002) Effects of insulin treatment in type 2 diabetic patients on intracellular lipid content in liver and skeletal muscle. Diabetes 51:3025–3032PubMedCrossRef
68.
Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R (2015) Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol 13:643–654, e641-649; quiz e639-640PubMedPubMedCentralCrossRef
69.
Haflidadottir S, Jonasson JG, Norland H et al (2014) Long-term follow-up and liver-related death rate in patients with non-alcoholic and alcoholic related fatty liver disease. BMC Gastroenterol 14:166PubMedPubMedCentralCrossRef
70.
Kim D, Kim WR, Kim HJ, Therneau TM (2013) Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 57:1357–1365PubMedPubMedCentralCrossRef
71.
Schwimmer JB, Behling C, Newbury R et al (2005) Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 42:641–649PubMedCrossRef
72.
Oni ET, Agatston AS, Blaha MJ et al (2013) A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 230:258–267PubMedCrossRef
73.
Targher G, Day CP, Bonora E (2010) Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363:1341–1350PubMedCrossRef
74.
Bhatia LS, Curzen NP, Calder PC, Byrne CD (2012) Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? Eur Heart J 33:1190–1200PubMedCrossRef
75.
Calori G, Lattuada G, Ragogna F et al (2011) Fatty liver index and mortality: the Cremona study in the 15th year of follow-up. Hepatology 54:145–152PubMedCrossRef
76.
Pacifico L, Chiesa C, Anania C, De Merulis A, Osborn JF, Romaggioli S et al (2014) Nonalcoholic fatty liver disease and the heart in children and adolescents. World J Gastroenterol 20:9055–9071PubMedPubMedCentral
77.
Dyson J, Jaques B, Chattopadyhay D et al (2014) Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol 60:110–117PubMedCrossRef
78.
Wong RJ, Cheung R, Ahmed A (2014) Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology 59:2188–2195PubMedCrossRef
79.
Musso G, Gambino R, Tabibian JH et al (2014) Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med 11, e1001680PubMedPubMedCentralCrossRef
80.
Targher G, Bertolini L, Chonchol M et al (2010) Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and retinopathy in type 1 diabetic patients. Diabetologia 53:1341–1348PubMedCrossRef
81.
Kim NH, Park J, Kim SH et al (2014) Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart 100:938–943PubMedCrossRef
82.
Hazlehurst JM, Tomlinson JW (2013) Non-alcoholic fatty liver disease in common endocrine disorders. Eur J Endocrinol 169:R27–R37PubMedCrossRef
83.
Lindor KD, Kowdley KV, Heathcote EJ et al (2004) Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 39:770–778PubMedCrossRef
84.
Bugianesi E, Gentilcore E, Manini R et al (2005) A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 100:1082–1090PubMedCrossRef
85.
Belfort R, Harrison SA, Brown K et al (2006) A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 355:2297–2307PubMedCrossRef
86.
Zelber-Sagi S, Kessler A, Brazowsky E et al (2006) A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 4:639–644PubMedCrossRef
87.
Dufour JF, Oneta CM, Gonvers JJ et al (2006) Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin E in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 4:1537–1543PubMedCrossRef
88.
Ratziu V, Giral P, Jacqueminet S et al (2008) Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 135:100–110PubMedCrossRef
89.
Aithal GP, Thomas JA, Kaye PV et al (2008) Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 135:1176–1184PubMedCrossRef
90.
Haukeland JW, Konopski Z, Eggesbo HB et al (2009) Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol 44:853–860PubMedCrossRef
91.
Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA (2009) Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 49:80–86PubMedCrossRef
92.
Shields WW, Thompson KE, Grice GA, Harrison SA, Coyle WJ (2009) The effect of metformin and standard therapy versus standard therapy alone in nondiabetic patients with insulin resistance and nonalcoholic steatohepatitis (NASH): a pilot trial. Therap Adv Gastroenterol 2:157–163PubMedPubMedCentralCrossRef
93.
Promrat K, Kleiner DE, Niemeier HM et al (2010) Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51:121–129PubMedPubMedCentralCrossRef
94.
Ratziu V, Charlotte F, Bernhardt C et al (2010) Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial. Hepatology 51:445–453PubMedCrossRef
95.
96.
Leuschner UF, Lindenthal B, Herrmann G et al (2010) High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology 52:472–479PubMedCrossRef
97.
Zein CO, Yerian LM, Gogate P et al (2011) Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology 54:1610–1619PubMedPubMedCentralCrossRef
98.
Lavine JE, Schwimmer JB, Van Natta ML et al (2011) Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 305:1659–1668PubMedPubMedCentralCrossRef
99.
Neuschwander-Tetri BA, Loomba R, Sanyal AJ et al (2015) Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385:956–965PubMedPubMedCentralCrossRef
100.
Valenti L, Fracanzani AL, Dongiovanni P et al (2014) A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia. World J Gastroenterol 20:3002–3010PubMedPubMedCentralCrossRef
101.
Takeshita Y, Takamura T, Honda M et al (2014) The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia 57:878–890PubMedCrossRef
102.
Sanyal AJ, Abdelmalek MF, Suzuki A, Cummings OW, Chojkier M, EPE-A Study Group (2014) No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology 147:377–384.e1PubMedCrossRef
103.
Loomba R, Sirlin CB, Ang B et al (2015) Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology 61:1239–1250PubMedPubMedCentralCrossRef
104.
Argo CK, Patrie JT, Lackner C et al (2015) Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J Hepatol 62:190–197PubMedPubMedCentralCrossRef
105.
Armstrong MJ, Gaunt P, Aithal GP et al (2015) Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 387:679–690PubMedCrossRef
106.
Zelber-Sagi S, Ratziu V, Oren R (2011) Nutrition and physical activity in NAFLD: an overview of the epidemiological evidence. World J Gastroenterol 17:3377–3389PubMedPubMedCentralCrossRef
107.
Boden G (2009) High- or low-carbohydrate diets: which is better for weight loss, insulin resistance, and fatty livers? Gastroenterology 136:1490–1492PubMedPubMedCentralCrossRef
108.
Lazo M, Solga SF, Horska A et al (2010) Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care 33:2156–2163PubMedPubMedCentralCrossRef
109.
Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE (2012) Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 379:2243–2251PubMedPubMedCentralCrossRef
110.
Thoma C, Day CP, Trenell MI (2012) Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 56:255–266PubMedCrossRef
111.
Ryan MC, Itsiopoulos C, Thodis T et al (2013) The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 59:138–143PubMedCrossRef
112.
113.
Kwon HK, Greenson JK, Conjeevaram HS (2014) Effect of lifetime alcohol consumption on the histological severity of non-alcoholic fatty liver disease. Liver Int 34:129–135PubMedCrossRef
114.
Dunn W, Sanyal AJ, Brunt EM et al (2012) Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol 57:384–391PubMedPubMedCentralCrossRef
115.
Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN (2010) The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 51:1972–1978PubMedCrossRef
116.
Saab S, Mallam D, Cox GA 2nd, Tong MJ (2014) Impact of coffee on liver diseases: a systematic review. Liver Int 34:495–504PubMedCrossRef
117.
Keating SE, Hackett DA, George J, Johnson NA (2012) Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 57:157–166PubMedCrossRef
118.
Bacchi E, Negri C, Targher G et al (2013) Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial). Hepatology 58:1287–1295PubMedCrossRef
119.
Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI (2005) Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54:603–608PubMedPubMedCentralCrossRef
120.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L et al (2015) Weight loss via lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 149:367–78.e5, quiz e14-e15PubMedCrossRef
121.
Rodriguez B, Torres DM, Harrison SA (2012) Physical activity: an essential component of lifestyle modification in NAFLD. Nat Rev Gastroenterol Hepatol 9:726–731PubMedCrossRef
122.
Adams LA, Sanderson S, Lindor KD, Angulo P (2005) The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 42:132–138PubMedCrossRef
123.
Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L, American Association for the Study of Liver Diseases, United States Food and Drug Administration (2015) Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology 61:1392–1405PubMedCrossRef
124.
Younossi ZM, Reyes MJ, Mishra A, Mehta R, Henry L (2014) Systematic review with meta-analysis: non-alcoholic steatohepatitis—a case for personalised treatment based on pathogenic targets. Aliment Pharmacol Ther 39:3–14PubMedCrossRef
125.
Mazzella N, Ricciardi LM, Mazzotti A, Marchesini G (2014) The role of medications for the management of patients with NAFLD. Clin Liver Dis 18:73–89PubMedCrossRef
126.
Ratziu V, Goodman Z, Sanyal A (2015) Current efforts and trends in the treatment of NASH. J Hepatol 62:S65–S75PubMedCrossRef
127.
Tiikkainen M, Häkkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Järvinen H (2004) Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 53:2169–2176PubMedCrossRef
128.
Bhalla K, Hwang BJ, Dewi RE et al (2012) Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis. Cancer Prev Res (Phila) 5:544–552CrossRef
129.
Zhang ZJ, Zheng ZJ, Shi R, Su Q, Jiang Q, Kip KE (2012) Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab 97:2347–2353PubMedCrossRef
130.
Vilsboll T, Christensen M, Junker AE, Knop FK, Gluud LL (2012) Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 344:d7771PubMedPubMedCentralCrossRef
131.
Hoofnagle JH, Van Natta ML, Kleiner DE et al (2013) Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 38:134–143PubMedCrossRef
132.
Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297:842–857PubMedCrossRef
133.
Schurks M, Glynn RJ, Rist PM, Tzourio C, Kurth T (2010) Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ 341:c5702PubMedPubMedCentralCrossRef
134.
Klein EA, Thompson IM Jr, Tangen CM et al (2011) Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306:1549–1556PubMedPubMedCentralCrossRef
135.
Mudaliar S, Henry RR, Sanyal AJ et al (2013) Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 145:574–582.e571PubMedCrossRef
136.
Parker HM, Johnson NA, Burdon CA, Cohn JS, O’Connor HT, George J (2012) Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 56:944–951PubMedCrossRef
137.
Dongiovanni P, Petta S, Mannisto V et al (2015) Statin use and nonalcoholic steatohepatitis in at risk individuals. J Hepatol 63:705–12PubMedCrossRef
138.
Valenti L, Fracanzani AL, Dongiovanni P et al (2007) Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case–control study. Am J Gastroenterol 102:1251–1258PubMedCrossRef
139.
Nobili V, Alisi A, Raponi M (2009) Pediatric non-alcoholic fatty liver disease: preventive and therapeutic value of lifestyle intervention. World J Gastroenterol 15:6017–6022PubMedPubMedCentralCrossRef
140.
Mitchel EB, Lavine JE (2014) Review article: the management of paediatric nonalcoholic fatty liver disease. Aliment Pharmacol Ther 40:1155–1170PubMedCrossRef
141.
Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P (2009) The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 58:1538–1544PubMedPubMedCentralCrossRef
142.
Schauer PR, Bhatt DL, Kirwan JP et al (2014) Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med 370:2002–2013PubMedCrossRef
143.
Caiazzo R, Lassailly G, Leteurtre E et al (2014) Roux-en-Y gastric bypass versus adjustable gastric banding to reduce nonalcoholic fatty liver disease: a 5-year controlled longitudinal study. Ann Surg 260:893–898, discussion 898–899PubMedCrossRef
144.
Lassailly G, Caiazzo R, Buob D et al (2015) Bariatric surgery reduces features of non-alcoholic steatohepatitis in morbidly obese patients. Gastroenterology 149:377–388CrossRef
145.
Charlton MR, Burns JM, Pedersen RA, Watt KD, Heimbach JK, Dierkhising RA (2011) Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 141:1249–1253PubMedCrossRef
146.
Wang X, Li J, Riaz DR, Shi G, Liu C, Dai Y (2014) Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 12:394–402, e391PubMedCrossRef
147.
Heuer M, Kaiser GM, Kahraman A et al (2012) Liver transplantation in nonalcoholic steatohepatitis is associated with high mortality and post-transplant complications: a single-center experience. Digestion 86:107–113PubMedCrossRef
148.
Sebagh M, Samuel D, Antonini TM et al (2012) Twenty-year protocol liver biopsies: invasive but useful for the management of liver recipients. J Hepatol 56:840–847PubMedCrossRef
Metadata
Title
EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
Authors
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)
Publication date
01-06-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 6/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-3902-y

Other articles of this Issue 6/2016

Diabetologia 6/2016 Go to the issue

Article

Life expectancy of type 1 diabetic patients during 1997–2010: a national Australian registry-based cohort study

Up front

Up front June 2016

Article

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway

Article

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis

Article

Antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial

Article

Changes in beta cell function occur in prediabetes and early disease in the Lepr db mouse model of diabetes
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 discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

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

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