1. 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;67:328-357.
2. 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.
4. Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020;158:1999-2014 e1.
5. Younossi ZM, Rinella ME, Sanyal A, Harrison SA, Brunt E, Goodman Z, et al. From NAFLD to MAFLD: implications of a premature change in terminology. Hepatology 2021;73:1194-1198.
6. Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015;62(1 Suppl):S47-S64.
8. 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;66:1138-1153.
10. Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015;61:1547-1554.
11. Kim D, Adejumo AC, Yoo ER, Iqbal U, Li AA, Pham EA, et al. Trends in mortality from extrahepatic complications in patients with chronic liver disease, from 2007 through 2017. Gastroenterology 2019;157:1055-1066 e11.
12. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010;363:1341-1350.
13. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-923.
14. Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol 2016;65:589-600.
16. Targher G, Byrne CD, Tilg H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut 2020;69:1691-1705.
18. Park HE, Kwak MS, Kim D, Kim MK, Cha MJ, Choi SY. Nonalcoholic fatty liver disease is associated with coronary artery calcification development: a longitudinal study. J Clin Endocrinol Metab 2016;101:3134-3143.
20. 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. J Hepatol 2016;64:1388-1402.
21. 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-e15.
24. 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. Hepatology 2011;53:1504-1514.
25. Chitturi S, Wong VW, Chan WK, Wong GL, Wong SK, Sollano J, et al. The Asia-Pacific working party on non-alcoholic fatty liver disease guidelines 2017-part 2: management and special groups. J Gastroenterol Hepatol 2018;33:86-98.
27. Wijarnpreecha K, Thongprayoon C, Edmonds PJ, Cheungpasitporn W. Associations of sugar- and artificially sweetened soda with nonalcoholic fatty liver disease: a systematic review and meta-analysis. QJM 2016;109:461-466.
28. Zelber-Sagi S, Ivancovsky-Wajcman D, Fliss Isakov N, Webb M, Orenstein D, Shibolet O, et al. High red and processed meat consumption is associated with nonalcoholic fatty liver disease and insulin resistance. J Hepatol 2018;68:1239-1246.
30. Gepner Y, Shelef I, Komy O, Cohen N, Schwarzfuchs D, Bril N, et al. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol 2019;71:379-388.
31. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34.
32. Asbaghi O, Choghakhori R, Ashtary-Larky D, Abbasnezhad A. Effects of the Mediterranean diet on cardiovascular risk factors in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis. Clin Nutr ESPEN 2020;37:148-156.
33. Saab S, Mallam D, Cox GA 2nd, Tong MJ. Impact of coffee on liver diseases: a systematic review. Liver Int 2014;34:495-504.
34. Nordestgaard AT, Nordestgaard BG. Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals. Int J Epidemiol 2016;45:1938-1952.
35. Chen YP, Lu FB, Hu YB, Xu LM, Zheng MH, Hu ED. A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease. Clin Nutr 2019;38:2552-2557.
36. Brown OI, Allgar V, Wong KY. Coffee reduces the risk of death after acute myocardial infarction: a meta-analysis. Coron Artery Dis 2016;27:566-572.
37. Kim D, Vazquez-Montesino LM, Li AA, Cholankeril G, Ahmed A. Inadequate physical activity and sedentary behavior are independent predictors of nonalcoholic fatty liver disease. Hepatology 2020;72:1556-1568.
38. Gerber L, Otgonsuren M, Mishra A, Escheik C, Birerdinc A, Stepanova M, et al. Nonalcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study. Aliment Pharmacol Ther 2012;36:772-781.
39. Shiroma EJ, Lee IM. Physical activity and cardiovascular health: lessons learned from epidemiological studies across age, gender, and race/ethnicity. Circulation 2010;122:743-752.
41. 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 (Lond) 2015;129:1097-1105.
42. Lin JS, O’Connor E, Evans CV, Senger CA, Rowland MG, Groom HC. Behavioral counseling to promote a healthy lifestyle in persons with cardiovascular risk factors: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2014;161:568-578.
43. Keating SE, Hackett DA, George J, Johnson NA. Exercise and nonalcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012;57:157-166.
44. Kim D, Murag S, Cholankeril G, Cheung A, Harrison SA, Younossi ZM, et al. Physical activity, measured objectively, is associated with lower mortality in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2020 Jul 16;doi:
10.1016/j.cgh.2020.07.023 .
45. 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;56:255-266.
46. Ismaiel A, Dumitrascu DL. How to reduce cardiovascular risk in nonalcoholic fatty liver disease. Am J Ther 2020 May 26;doi:
10.1097/MJT.0000000000001174.
50. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010;52:79-104.
52. Aithal GP, Thomas JA, Kaye PV, Lawson A, Ryder SD, Spendlove I, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008;135:1176-1184.
53. 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;165:305-315.
56. Zhu J, Yu X, Zheng Y, Li J, Wang Y, Lin Y, et al. Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map. Lancet Diabetes Endocrinol 2020;8:192-205.
57. Armstrong MJ, Houlihan DD, Rowe IA, Clausen WH, Elbrønd B, Gough SC, et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment Pharmacol Ther 2013;37:234-242.
58. Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, 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.
59. Petit JM, Cercueil JP, Loffroy R, Denimal D, Bouillet B, Fourmont C, et al. Effect of liraglutide therapy on liver fat content in patients with inadequately controlled type 2 diabetes: the lira-NAFLD study. J Clin Endocrinol Metab 2017;102:407-415.
60. Svanström H, Ueda P, Melbye M, Eliasson B, Svensson AM, Franzén S, et al. Use of liraglutide and risk of major cardiovascular events: a register-based cohort study in Denmark and Sweden. Lancet Diabetes Endocrinol 2019;7:106-114.
61. Howell R, Wright AM, Clements JN. Clinical potential of liraglutide in cardiovascular risk reduction in patients with type 2 diabetes: evidence to date. Diabetes Metab Syndr Obes 2019;12:505-512.
65. Singh M, Kumar A. Risks associated with SGLT2 inhibitors: an overview. Curr Drug Saf 2018;13:84-91.
66. Yilmaz Y, Yonal O, Deyneli O, Celikel CA, Kalayci C, Duman DG. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg 2012;75:240-244.
67. Iwasaki T, Yoneda M, Inamori M, Shirakawa J, Higurashi T, Maeda S, 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.
70. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;373:232-242.
72. Kohsaka S, Lam CSP, Kim DJ, Cavender MA, Norhammar A, Jørgensen ME, et al. Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors: an analysis from the CVD-REAL 2 multinational cohort study. Lancet Diabetes Endocrinol 2020;8:606-615.
73. Athyros VG, Alexandrides TK, Bilianou H, Cholongitas E, Doumas M, Ganotakis ES, et al. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis and related cardiovascular risk. An expert panel statement. Metabolism 2017;71:17-32.
74. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol 2019;74:1376-1414.
75. Hyogo H, Tazuma S, Arihiro K, Iwamoto K, Nabeshima Y, Inoue M, et al. Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. Metabolism 2008;57:1711-1718.
76. Ekstedt M, Franzén LE, Mathiesen UL, Holmqvist M, Bodemar G, Kechagias S. Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study. J Hepatol 2007;47:135-141.
77. Kimura Y, Hyogo H, Yamagishi S, Takeuchi M, Ishitobi T, Nabeshima Y, et al. Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH. J Gastroenterol 2010;45:750-757.
78. Foster T, Budoff MJ, Saab S, Ahmadi N, Gordon C, Guerci AD. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol 2011;106:71-77.
79. Lewis JH, Mortensen ME, Zweig S, Fusco MJ, Medoff JR, Belder R, et al. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology 2007;46:1453-1463.
81. Tzefos M, Olin JL. 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor use in chronic liver disease: a therapeutic controversy. J Clin Lipidol 2011;5:450-459.
82. 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.
84. Lan M, Nguyen T, Gray S. Omega-3 fatty acid supplements for the prevention of cardiovascular disease. Sr Care Pharm 2020;35:318-323.
87. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003;361:2017-2023.
88. Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004;39:770-778.
89. Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman Z, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2019;394:2184-2196.
91. Jiang ZG, Feldbrügge L, Tapper EB, Popov Y, Ghaziani T, Afdhal N, et al. Aspirin use is associated with lower indices of liver fibrosis among adults in the United States. Aliment Pharmacol Ther 2016;43:734-743.
93. Lee Y, Doumouras AG, Yu J, Brar K, Banfield L, Gmora S, et al. Complete resolution of nonalcoholic fatty liver disease after bariatric surgery: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2019;17:1040-1060.e11.
94. Klebanoff MJ, Corey KE, Chhatwal J, Kaplan LM, Chung RT, Hur C. Bariatric surgery for nonalcoholic steatohepatitis: a clinical and cost-effectiveness analysis. Hepatology 2017;65:1156-1164.
95. Mathurin P, Hollebecque A, Arnalsteen L, Buob D, Leteurtre E, Caiazzo R, 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.
97. Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology 2015;149:379-388 quiz e15-e16.
98. Moussa O, Ardissino M, Heaton T, Tang A, Khan O, Ziprin P, et al. Effect of bariatric surgery on long-term cardiovascular outcomes: a nationwide nested cohort study. Eur Heart J 2020;41:2660-2667.
101. Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002;35:373-379.
102. Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol 2019;71:793-801.
103. Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis. Diabetes Care 2018;41:372-382.
104. Armstrong MJ, Adams LA, Canbay A, Syn WK. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 2014;59:1174-1197.
105. Noureddin M, Jones C, Alkhouri N, Gomez EV, Dieterich DT, Rinella ME, et al. Screening for nonalcoholic fatty liver disease in persons with type 2 diabetes in the United States is cost-effective: a comprehensive cost-utility analysis. Gastroenterology 2020;159:1985-1987.
106. Targher G, Chonchol M, Zoppini G, Abaterusso C, Bonora E. Risk of chronic kidney disease in patients with non-alcoholic fatty liver disease: is there a link? J Hepatol 2011;54:1020-1029.
108. Targher G, Bertolini L, Rodella S, Zoppini G, Lippi G, Day C, et al. Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients. Diabetologia 2008;51:444-450.
110. Byrne CD, Targher G. NAFLD as a driver of chronic kidney disease. J Hepatol 2020;72:785-801.
114. Wijarnpreecha K, Thongprayoon C, Boonpheng B, Panjawatanan P, Sharma K, Ungprasert P, et al. Nonalcoholic fatty liver disease and albuminuria: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2018;30:986-994.
119. Jin S, Jiang S, Hu A. Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Sleep Breath 2018;22:841-851.
121. Aron-Wisnewsky J, Minville C, Tordjman J, Lévy P, Bouillot JL, Basdevant A, et al. Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol 2012;56:225-233.
122. Mishra P, Nugent C, Afendy A, Bai C, Bhatia P, Afendy M, et al. Apnoeic-hypopnoeic episodes during obstructive sleep apnoea are associated with histological nonalcoholic steatohepatitis. Liver Int 2008;28:1080-1086.
123. Trzepizur W, Boursier J, Mansour Y, Le Vaillant M, Chollet S, Pigeanne T, et al. Association between severity of obstructive sleep apnea and blood markers of liver injury. Clin Gastroenterol Hepatol 2016;14:1657-1661.
125. Schwartz AR, Gold AR, Schubert N, Stryzak A, Wise RA, Permutt S, et al. Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1991;144(3 Pt 1):494-498.
126. Smith PL, Gold AR, Meyers DA, Haponik EF, Bleecker ER. Weight loss in mildly to moderately obese patients with obstructive sleep apnea. Ann Intern Med 1985;103:850-855.
127. Chung GE, Kim D, Kwak MS, Yim JY, Ahmed A, Kim JS. Longitudinal change in thyroid-stimulating hormone and risk of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2021;19:848-849.e1.
129. Chung GE, Kim D, Kim W, Yim JY, Park MJ, Kim YJ, et al. Nonalcoholic fatty liver disease across the spectrum of hypothyroidism. J Hepatol 2012;57:150-156.
132. Kim D, Kim W, Joo SK, Bae JM, Kim JH, Ahmed A. Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis. Clin Gastroenterol Hepatol 2018;16:123-131.e1.
133. Kim D, Vazquez-Montesino LM, Escober JA, Fernandes CT, Cholankeril G, Loomba R, et al. Low thyroid function in nonalcoholic fatty liver disease is an independent predictor of all-cause and cardiovascular mortality. Am J Gastroenterol 2020;115:1496-1504.
134. Kelly MJ, Pietranico-Cole S, Larigan JD, Haynes NE, Reynolds CH, Scott N, et al. Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a highly selective thyroid hormone receptor beta agonist in clinical trials for the treatment of dyslipidemia. J Med Chem 2014;57:3912-3923.
136. Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA, Frias JP, et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebocontrolled, phase 2 trial. Lancet 2019;394:2012-2024.
137. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and Pcos Society Disease State clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome--part 1. Endocr Pract 2015;21:1291-1300.
139. Kim JJ, Kim D, Yim JY, Kang JH, Han KH, Kim SM, et al. Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2017;45:1403-1412.
141. Paschou SA, Polyzos SA, Anagnostis P, Goulis DG, Kanaka-Gantenbein C, Lambrinoudaki I, et al. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Endocrine 2020;67:1-8.
143. Miele L, Vallone S, Cefalo C, La Torre G, Di Stasi C, Vecchio FM, et al. Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol 2009;51:778-786.
144. Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol 2009;51:758-764.
145. Wenk KS, Arrington KC, Ehrlich A. Psoriasis and non-alcoholic fatty liver disease. J Eur Acad Dermatol Venereol 2011;25:383-391.
146. Phan K, Onggo J, Charlton O, Smith SD. Relationship between psoriasis and non-alcoholic fatty liver disease - updated systematic review and adjusted meta-analysis. Australas J Dermatol 2019;60:e352-e355.
147. Campanati A, Ganzetti G, Di Sario A, Damiani A, Sandroni L, Rosa L, et al. The effect of etanercept on hepatic fibrosis risk in patients with non-alcoholic fatty liver disease, metabolic syndrome, and psoriasis. J Gastroenterol 2013;48:839-846.