Buzzetti E, Pinzani M, Tsochatziz EA. The multiple-hit pathogensesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65:1038–48.
CAS
PubMed
Google Scholar
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.
PubMed
Google Scholar
Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: a systematic review with comparative analysis. World J Gastroenterol. 2018;24:3361–73.
PubMed
PubMed Central
Google Scholar
Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW. Nonalcoholic fatty disease in adults: current concepts in etiology, outcomes, and management. Endocrine Rev. 2020;41:66–117.
Google Scholar
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.
PubMed
Google Scholar
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;64:1388–402.
Google Scholar
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.
PubMed
Google Scholar
Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202–9.
NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387:1377–96.
Google Scholar
Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde, Departamento de Análise em Saúde e Vigilância de Doenças não Transmissíveis. Vigitel Brasil 2018: vigilância de fatores de risco e proteção para doenças crônicas por inquérito telefônico: estimativas sobre frequência e distribuição sociodemográfica de fatores de risco e proteção para doenças crônicas nas capitais dos 26 estados brasileiros e no Distrito Federal em 2018. Brasília: Ministério da Saúde, 2019. https://portalarquivos2.saude.gov.br/images/pdf/2019/julho/25/vigitel-brasil-2018.pdf.
Pallayova M, Taheri S. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies. Clin Obes. 2014;4:243–53.
CAS
PubMed
Google Scholar
Perumpail B, Muhammad AK, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23(47):8263–76.
PubMed
PubMed Central
Google Scholar
Ross R, Neeland IJ, Yamashita S, Shai I, Seidel J, Magni P, et al. Waist circumference as a vital sign in clinical practice: a consensus statement from the IAS and ICCR working group on visceral obesity. Nat Rev Endocrinol. 2020;16:177–89.
PubMed
PubMed Central
Google Scholar
Kim D, Chung GE, Kwak MS, Seo HB, Kang JH, Kim W, et al. Body fat distribution and risk of incident and regressed nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14(1):132–8.
PubMed
Google Scholar
Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365(9468):1415–28.
CAS
PubMed
Google Scholar
Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome-a new worldwide definition. Lancet. 2005;366:1059–62.
PubMed
Google Scholar
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–52.
PubMed
Google Scholar
Moore JX, Chaudhary N, Akinyemiju T. Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Prev Chronic Dis. 2017;14:160287.
Google Scholar
Saklayen MG. The global epidemic of the metabolic syndrome. Curr Hypertens Rep. 2018;20(2):12.
PubMed
PubMed Central
Google Scholar
van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, Doiron D, Fisher K, Foco L, et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord. 2014;14:9.
PubMed
PubMed Central
Google Scholar
Jinjuvadia R, Antaki F, Lohia P, Liangpunsakul S. The association between nonalcoholic fatty liver disease and metabolic abnormalities in United States population. J Clin Gastroenterol. 2017;51:160–6.
CAS
PubMed
PubMed Central
Google Scholar
International Diabetes Federation. IDF Diabetes Atlas, 9th ed. Brussels, Belgium: 2019. https://www.diabetesatlas.org.
Cusi K. Time to include nonalcoholic steatohepatitis in the management of patients with type 2 diabetes. Diabetes Care. 2020;43(2):275–9.
PubMed
Google Scholar
Dai W, Ye L, Liu A, Wen SW, Deng J, Wu X, Lai Z. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a meta-analysis. Medicine. 2017;96:e8179.
PubMed
PubMed Central
Google Scholar
Younossi ZM, Golabi P, 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.
PubMed
Google Scholar
Shulman GI. Ectopic fat in insulin resistance, dyslipidemia and cardiometabolic disease. N Engl J Med. 2014;371:1131–41.
PubMed
Google Scholar
Virtue S, Vidal-Puig A. It’s not how fat you are, it’s what you do with it that counts. PLoS Biol. 2008;23:6.
Google Scholar
Stein DT, Szczepaniak L, Garg A, Malloy C, McGarry JD. Intramuscular lipid is increased in subjects with congenital generalized lipodystrophy (Abstract). Diabetes. 1997;46(Suppl. 1):242A.
Google Scholar
Hussain I, Patni N, Ueda M, Sorkina E, Valerio CM, Cochran E, et al. A novel generalized lipodystrophy-associated progeroid syndrome due to recurrent heterozygous LMNA p.T10I mutation. J Clin Endocrinol Metab. 2018;103(3):1005–14.
PubMed
Google Scholar
Godoy-Matos AF, Valerio CM, Moreira RO, Momesso DP, Bittencourt LK. Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy. Diabetol Metab Syndr. 2018;10:71.
PubMed
PubMed Central
Google Scholar
Sociedade Brasileira de Diabetes. Diretrizes da Sociedade Brasileira de Diabetes 2019–2020. Sao Paulo: Clannad; 2019. p. 489. https://www.diabetes.org.br/profissionais/images/DIRETRIZES-COMPLETA-2019-2020.pdf.
Godoy-Matos AF, Bahia LR, Domingues RC, Tambascia M, Geloneze B, Kraemer-Aguiar LG, et al. Rosiglitazone decreases intra- to extramyocellular fat ratio in obese non-diabetic adults with metabolic syndrome. Diabet Med. 2010;27:23–9.
CAS
PubMed
Google Scholar
Gavrila A, Chan JL, Yiannakouris N, Kontogianni M, Miller LC, Orlova C, et al. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocrinol Metab. 2003;88:4823–31.
CAS
PubMed
Google Scholar
Pellegrinelli V, Carobbio S, Vidal-Puig A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia. 2016;59:1075–88.
CAS
PubMed
PubMed Central
Google Scholar
Stefan N, Schick F, Häring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab. 2017;26:292–300.
CAS
PubMed
Google Scholar
Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet. 2017;49:17–26.
CAS
PubMed
Google Scholar
Bril F, Barb D, Portillo-Sanchez P, Biernacki D, Lomonaco R, Suman A, et al. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease. Hepatology. 2017;65(4):1132–44.
CAS
PubMed
Google Scholar
Rotman A, Neuschwander-Tetri BA. Liver fat accumulation as a barometer of insulin responsiveness again points to adipose tissue as the culprit. Hepatology. 2017;65:1090–8.
Google Scholar
Younossis Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, prediction, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20.
Google Scholar
Sliz E, Sebert S, Würtz P, Kangas AJ, Soininen P, Lehtimäki T, et al. NAFLD risk alleles in PNPLA3, TM6SF2, GCKR and LYPLAL1 show divergent metabolic effect. Human Mol Gen. 2018;27(12):2214–23.
CAS
Google Scholar
Godoy-Matos AF. The role of glucagon on type 2 diabetes at a glance. Diabetol Metab Syndr. 2014;6:91.
PubMed
PubMed Central
Google Scholar
Knop FK. A gut feeling about glucagon. Eur J Endocrinol. 2018;178:R267–8.
CAS
PubMed
Google Scholar
Holst JJ, Wewer Albrechtsen NJ, Pedersen J, Knop FK. Glucagon and amino acids are linked in a mutual feedback cycle: the liver-α-cell axis. Diabetes. 2017;66(2):235–40.
CAS
PubMed
Google Scholar
Longuet C, Robledo AM, Dean ED, Dai C, Ali S, McGuinness I, et al. Liver-specific disruption of the murine glucagon receptor produces α-cell hyperplasia: evidence for a circulating α-cell growth factor. Diabetes. 2013;62:1196–205.
CAS
PubMed
PubMed Central
Google Scholar
Dean ED, Li M, Prasad N, Wisniewski SN, Von Deylen A, Spaeth J, et al. Interrupted glucagon signaling reveals hepatic alpha cell axis and role for l-glutamine in α cell proliferation. Cell Metab. 2017;25:1362–73.
CAS
PubMed
PubMed Central
Google Scholar
Knop FK, Aaboe K, Vilsbøll T, Vølund A, Holst JJ, Krarup T, Madsbad S. Impaired incretin effect and fasting hyperglucagonemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diab Obes Metabol. 2012;14:500–10.
CAS
Google Scholar
Suppli MP, Bagger JI, Lund A, Demant M, van Hall M, Strandberget C, et al. Glucagon resistance at the level of amino acid turnover in obese subjects with hepatic steatosis. Diabetes. 2020. https://doi.org/10.2337/db19-0715.
Article
PubMed
Google Scholar
Junker AE, Gluud L, Holst JJ, Knop FK, Vilsbøll T. Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia. J Intern Med. 2016;279(5):485–93.
CAS
PubMed
Google Scholar
Wewer Albrechtsen NJ, Junker AE, Christensen M, Hædersdal S, Wibrand F, Lund AM, et al. Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes. Am J Physiol Gastrointest Liver Physiol. 2018;314(1):G91–6.
PubMed
Google Scholar
Wewer Albrechtsen NJ, Færch K, Jensen TM, Witte DR, Pedersen J, Mahendran Y, et al. Evidence of a liver-alpha cell axis in humans: hepatic insulin resistance attenuates relationship between fasting plasma glucagon and glucagon inotropic amino acids. Diabetologia. 2018;61:671–80.
CAS
PubMed
Google Scholar
Lund A, Bagger JI, Albrechtsen NJW, Christensen M, Grøndahl M, Hansen CP, et al. Increased liver fat content in totally pancreatectomized patients. Diabetes. 2017;66:A674–88.
Google Scholar
Guzman CB, Zhang XM, Liu R, Regev A, Shankar S, Garhyan P, et al. Treatment with LY2409021, a glucagon receptor antagonist, increases liver fat in patients with type 2 diabetes. Diabetes Obes Metab. 2017;19:1521–8.
CAS
PubMed
Google Scholar
Albrechtsen NJW, Pedersen J, Galsgaard KD, Winther-Sorensen M, Suppli MP, Janah L, et al. The liver-α-cell axis and type 2 diabetes. Endocr Rev. 2019;40(5):1353–66.
Google Scholar
Kitade I, Chen G, Ni Y, Ota T. Nonalcoholic fatty liver disease and insulin resistance: new insights and potential new treatments. Nutrients. 2017;9(4):E387.
PubMed
Google Scholar
Sheka AC, Adeyi O, Thompson J, Hameed B, Crawford PA, Ikramuddin S. Nonalcoholic steatohepatitis: a review. JAMA. 2020;323(12):1175–83.
CAS
PubMed
Google Scholar
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system. For nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.
PubMed
Google Scholar
Bedossa P, Poitou C, Veyrie N, Bouillot J-L, Basdevant A, Paradis V, et al. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients. Hepatology. 2012;56:1751–9.
PubMed
Google Scholar
Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20(2):475–85.
PubMed
PubMed Central
Google Scholar
Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54:1082–90.
PubMed
Google Scholar
Siddiqui MS, Harrison SA, Abdelmalek MF, Anstee QM, Bedossa P, Castera L, Liver Forum Case Definitions Working Group, et al. Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science. Hepatology. 2018;67(5):2001–12.
PubMed
Google Scholar
Shi KQ, Tang JZ, Zhu XL, Ying L, Li DW, Gao J, et al. Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: a meta-analysis of diagnostic accuracy. J Gastroenterol Hepatol. 2014;29:1115–49.
Google Scholar
Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology. 2017;152:598–607.
PubMed
Google Scholar
Petta S, Wong VW, Camma C, Hiriart JB, Wong GL, Vergniol J, et al. Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD. Aliment Pharmacol Ther. 2017;46(6):617–27.
CAS
PubMed
Google Scholar
Loomba R, Wolfson T, Ang B, Hooker J, Behling C, Peterson M, et al. Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: a prospective study. Hepatology. 2014;60:1920–8.
CAS
PubMed
Google Scholar
Xiao G, Zhu S, Xiao X, Yan L, Yang J, Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: a meta-analysis. Hepatology. 2017;66(5):1486–501.
CAS
PubMed
Google Scholar
Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–25.
CAS
PubMed
Google Scholar
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(4):846–54.
CAS
PubMed
Google Scholar
Castera L, Friedrich-Rust M, Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology. 2019;156(5):1264–81.
PubMed
Google Scholar
Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33.
PubMed
PubMed Central
Google Scholar
Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K, Bergholm R, Johansson LM, et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009;137:865–72.
CAS
PubMed
Google Scholar
Lee JH, Kim D, Kim HJ, Lee CH, Yang JI, Kim W, et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010;42:503–8.
CAS
PubMed
Google Scholar
Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V, Theodorou I, et al. Liver fibrosis in overweight patients. Gastroenterology. 2000;118(6):1117–23.
CAS
PubMed
Google Scholar
Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518–26.
PubMed
Google Scholar
Altamirano J, Qi Q, Choudhry S, Abdallah M, Singal AK, Humar A, et al. Non-invasive diagnosis: non-alcoholic fatty liver disease and alcoholic liver disease. Transl Gastroenterol Hepatol. 2020;5(5):31.
PubMed
PubMed Central
Google Scholar
Siddiqui MS, Yamada G, Vuppalanchi R, Natta MV, Loomba R, Guy C, et al. Diagnostic accuracy of noninvasive fibrosis models to detect change in fibrosis stage. Clin Gastroenterol Hepatol. 2019;17(9):1877–85.
PubMed
PubMed Central
Google Scholar
Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics. Metabolism. 2019;92:82–97.
CAS
PubMed
Google Scholar
Hannah WN Jr, Harrison SA. Effect of weight loss, diet, exercise, and bariatric surgery on nonalcoholic fatty liver disease. Clin Liver Dis. 2016;20:339–50.
PubMed
Google Scholar
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(3):561–8.
PubMed
Google Scholar
Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia. 2012;55(4):885–904.
CAS
PubMed
Google Scholar
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(2):367–78.
PubMed
Google Scholar
Brunner KT, Henneberg CJ, Wilechansky RM, Long MT. Nonalcoholic fatty liver disease and obesity treatment. Curr Obes Rep. 2019;8(3):220–8.
PubMed
PubMed Central
Google Scholar
Ratziu V, Ghabril M, Romero-Gomez M, Svegliati-Baroni G. Recommendations for management and treatment of nonalcoholic steatohepatitis. Transplantation. 2019;103(1):28–38.
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
Anania C, Perla FM, Olivero F, Pacifico L, Chiesa C. Mediterranean diet and nonalcoholic fatty liver disease. World J Gastroenterol. 2018;24:2083–94.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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. 2018;97:e12271.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
Sanyal AJ, Abdelmalek MF, Suzuki A, Cummings OW, Chojkier M, EPE-A Study Group. No significant effects of ethyleicosapentanoic acid on histologic features of non-alcoholic steatohepatitis in a phase 2 trial. Gastroenterology. 2014;147:377–84.
CAS
PubMed
Google Scholar
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
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 Nutr. 2014;33:678–83.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society. Circulation. 2014;129:S102–38.
PubMed
Google Scholar
Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, et al. European guidelines for obesity management in adults. Obes Facts. 2015;8:402–24.
PubMed
PubMed Central
Google Scholar
Acosta A, Streett S, Kroh MD, Cheskin LJ, Saunders KH, Kurian M, et al. White paper AGA: POWER -practice guide on obesity and weight management, education, and resources. Clin Gastroenterol Hepatol. 2017;15:631–49.
PubMed
Google Scholar
Gupta NA, Mells J, Dunham RM, Grakoui A, Handy J, Saxena NK, et al. Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway. Hepatology. 2010;51(5):1584–92.
CAS
PubMed
Google Scholar
Armstrong MJ, Hull D, Guo K, Barton D, Hazlehurst JM, Gathercole LL, et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J Hepatol. 2016;64:399–408.
CAS
PubMed
PubMed Central
Google Scholar
Gastaldelli A, Gaggini M, Daniele G, Ciociaro D, Cersosimo E, Tripathy D, et al. Exenatide improves both hepatic and adipose tissue insulin resistance: a dynamic positron emission tomography study. Hepatology. 2016;64:2028–37.
CAS
PubMed
Google Scholar
Upadhyay J, Polyzos SA, Perakakis N, Thakkar B, Paschou SA, Katsiki N, et al. Pharmacotherapy of type 2 diabetes: an update. Metabolism. 2018;78:13–42.
CAS
PubMed
Google Scholar
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373(1):11–22.
PubMed
Google Scholar
Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315(22):2424–34.
CAS
PubMed
PubMed Central
Google Scholar
Liu Y, Wei R, Hong TP. Potential roles of glucagon-like peptide-1-based therapies in treating non-alcoholic fatty liver disease. World J Gastroentol. 2014;20(27):9090–7.
Google Scholar
Wang Y, Parlevliet ET, Geerling JJ, van der Tuin SJ, Zhang H, Bieghs V, et al. Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration. Br J Pharmacol. 2014;171:723–34.
CAS
PubMed
PubMed Central
Google Scholar
Zhang L, Yang M, Ren H, Hu H, Boden G, Li L, Yang G. GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK. Liver Int. 2013;33(5):788–94.
Google Scholar
Xu F, Li Z, Zheng X, Liu H, Liang H, Xu H, Chen Z, et al. SIRT1 mediates the effect of GLP-1 receptor agonist exenatide on ameliorating hepatic steatosis. Diabetes. 2014;63(11):3637–46.
CAS
PubMed
Google Scholar
Khoo J, Hsiang J, Taneja R, Law NM, Ang TL. Comparative effects of liraglutide 3 mg vs structured lifestyle modification on body weight, liver fat and liver function in obese patients with non-alcoholic fatty liver disease: a pilot randomized trial. Diabetes Obes Metab. 2017;19:1814–7.
CAS
PubMed
Google Scholar
Novo Nordisk. Company announcement No 28/2020. Denmark: Novo Nordisk; 6 May 2020. p. 29. https://www.novonordisk.com/content/dam/Denmark/HQ/investors/irmaterial/quarterly_financial_reports/2020/Financial%20report%20for%20Q1%202020.pdf.
Assy N, Hussein O, Abassi Z. Weight loss induced by orlistat reverses fatty infiltration and improves hepatic fibrosis in obese patients with non-alcoholic steatohepatitis. Gut. 2007;56(3):443–4.
PubMed
PubMed Central
Google Scholar
Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology. 2009;49:80–6.
CAS
PubMed
Google Scholar
Harrison SA, Fincke C, Helinski D, Torgerson S, Hayashi P. A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther. 2004;20:623–8.
CAS
PubMed
Google Scholar
Kelley DE, Kuller LH, McKolanis TM, Harper P, Mancino J, Kalhan S. Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes. Diabetes Care. 2004;27:33–40.
CAS
PubMed
Google Scholar
Zelber-Sagi S, Kessler A, Brazowsky E, Webb M, Lurie Y, Santo M, et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006;4:639–44.
CAS
PubMed
Google Scholar
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.
PubMed
Google Scholar
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.
PubMed
Google Scholar
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.
PubMed
Google Scholar
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.
PubMed
Google Scholar
Fakhry TK, Mhaskar R, Schwitalla T, Muradova E, Gonzalvo JP, Murr MM. Bariatric surgery improves nonalcoholic fatty liver disease: a contemporary systematic review and meta-analysis. Surg Obes Relat Dis. 2019;15(3):502–11.
PubMed
Google Scholar
Mantovani A, Byrne CD, Scorletti E, Mantzoros CS, Targher G. Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials. Diabetes Metab. 2020. https://doi.org/10.1016/j.diabet.2019.12.007
Haukeland JW, Konopski Z, Eggesbø HB, von Volkmann HL, Raschpichler G, Bjøro K, et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009;44(7):853–60.
CAS
PubMed
Google Scholar
Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305:1659–68.
CAS
PubMed
PubMed Central
Google Scholar
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(18):1675–85.
CAS
PubMed
PubMed Central
Google Scholar
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(4):1176–84.
CAS
PubMed
Google Scholar
Musso G, Cassader M, Paschetta E, Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis. JAMA Intern Med. 2017;177(5):633–40.
PubMed
PubMed Central
Google Scholar
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(1):37–46.
CAS
PubMed
Google Scholar
Schürks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010;341:c5702.
PubMed
PubMed Central
Google Scholar
Abner EL, Schmitt FA, Mendiondo MS, Marcum JL, Kryscio RJ. Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci. 2011;4(2):158–70.
CAS
PubMed
PubMed Central
Google Scholar
Sanyal AJ, Harrison SA, Ratziu V, Abdelmalek MF, Diehl AM, Caldwell S, et al. The natural history of advanced fibrosis due to nonalcoholic steatohepatitis: data from the simtuzumab trials. Hepatology. 2019;70(6):1913–27.
CAS
PubMed
Google Scholar
Blazina I, Selph S. Diabetes drugs for nonalcoholic fatty liver disease: a systematic review. Syst Rev. 2019;8(1):295.
PubMed
PubMed Central
Google Scholar
Chen HP, Shieh JJ, Chang CC, Chen TT, Lin JT, Wu MS, et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut. 2013;62(4):606–15.
CAS
PubMed
Google Scholar
Ravikumar B, Gerrard J, Dalla Man C, Firbank MJ, Lane A, English PT, et al. Pioglitazone decreases fasting and postprandial endogenous glucose production in proportion decrease in hepatic triglyceride content. Diabetes. 2008;57:2288–95.
CAS
PubMed
PubMed Central
Google Scholar
Tang W, Xu Q, Hong T, Tong G, Feng W, Shen S, et al. Comparative efficacy of anti-diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized and non-randomized studies. Diabetes Metab Res Rev. 2016;32(2):200–16.
PubMed
Google Scholar
Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355(22):2297–307.
CAS
PubMed
Google Scholar
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(5):305–15.
PubMed
Google Scholar
Bril F, Biernack DM, Kalavalapalli S, Lomonaco R, Subbarayan SK, Lai J, et al. Role of vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: a randomized controlled trial. Diab Care. 2019;42:1481–8.
CAS
Google Scholar
Silva Júnior WS, Godoy-Matos AF, Kraemer-Aguiar LG. Dipeptidyl peptidase 4: a new link between diabetes mellitus and atherosclerosis? Biomed Res Int. 2015;2015:816164.
PubMed
PubMed Central
Google Scholar
Silva Júnior WS, Souza MDGC, Kraemer-Aguiar LG. Dipeptidyl peptidase 4 (DPP4), adipose inflammation, and insulin resistance: is it time to look to the hepatocyte? Hepatobiliary Surg Nutr. 2018;7(6):499–500.
PubMed
PubMed Central
Google Scholar
Itou M, Kawaguchi T, Taniguchi E, Sata M. Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol. 2013;19(15):2298–306.
CAS
PubMed
PubMed Central
Google Scholar
Silva Júnior WS, Souza MDGC, Nogueira Neto JF, Bouskela E, Kraemer-Aguiar LG. Dipeptidyl peptidase 4 activity is related to body composition, measures of adiposity, and insulin resistance in subjects with excessive adiposity and different degrees of glucose tolerance. J Diabetes Res. 2019;2019:5238013.
PubMed
PubMed Central
Google Scholar
Ghorpade DS, Ozcan L, Zheng Z, Nicoloro SM, Shen Y, Chen E, et al. Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature. 2018;555(7698):673–7.
CAS
PubMed
PubMed Central
Google Scholar
Macauley M, Hollingsworth KG, Smith FE, Thelwall PE, Al-Mrabeh A, Schweizer A, et al. Effect of vildagliptin on hepatic steatosis. J Clin Endocrinol Metab. 2015;100(4):1578–85.
CAS
PubMed
PubMed Central
Google Scholar
Deng XL, Ma R, Zhu HX, Zhu J. Short article: a randomized-controlled study of sitagliptin for treating diabetes mellitus complicated by nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2017;29(3):297–301.
CAS
PubMed
Google Scholar
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(2):234–42.
CAS
PubMed
Google Scholar
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(10019):679–90.
CAS
PubMed
Google Scholar
Newsome P, Francque S, Harrison S, Ratziu V, Van Gaal L, Calanna S, et al. Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity. Aliment Pharmacol Ther. 2019;50(2):193–203.
CAS
PubMed
PubMed Central
Google Scholar
Dokmak A, Almeqdadi M, Trivedi H, Krishnan S. Rise of sodium-glucose cotransporter 2 inhibitors in the management of nonalcoholic fatty liver disease. World J Hepatol. 2019;11(7):562–73.
PubMed
PubMed Central
Google Scholar
Raj H, Durgia H, Palui R, Kamalanathan S, Selvarajan S, Kar SS, et al. SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: a systematic review. World J Diabetes. 2019;10(2):114–32.
PubMed
PubMed Central
Google Scholar
Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir JS, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care. 2018;41(8):1801–8.
CAS
PubMed
Google Scholar
Sattar N, Fitchett D, Hantel S, George JT, Zinman B. Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial. Diabetologia. 2018;61(10):2155–63.
CAS
PubMed
PubMed Central
Google Scholar
Shimizu M, Suzuki K, Kato K, Jojima T, Iijima T, Murohisa T, et al. Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obes Metab. 2019;21(2):285–92.
CAS
PubMed
Google Scholar
Eriksson JW, Lundkvist P, Jansson PA, Johansson L, Kvarnström M, Moris L, et al. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study. Diabetologia. 2018;61(9):1923–34.
CAS
PubMed
PubMed Central
Google Scholar
Li B, Wang Y, Ye Z, Yang H, Cui X, Wang Z, et al. Effects of canagliflozin on fatty liver indexes in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. J Pharm Pharm Sci. 2018;21(1):222–35.
PubMed
Google Scholar
Akuta N, Kawamura Y, Watanabe C, Nishimura A, Okubo M, Mori Y, et al. Impact of sodium glucose cotransporter 2 inhibitor on histological features and glucose metabolism of non-alcoholic fatty liver disease complicated by diabetes mellitus. Hepatol Res. 2019;49(5):531–9.
CAS
PubMed
Google Scholar
Maffioli P, Fogari E, D’Angelo A, Perrone T, Derosa G. Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin. Eur J Gastroenterol Hepatol. 2013;25(9):1113–22.
PubMed
Google Scholar
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. J Diabetes. 2017;9(8):800–9.
CAS
PubMed
Google Scholar
Morita Y, Ueno T, Sasaki N, Tateishi Y, Nagata E, Kage M, et al. Nateglinide is useful for nonalcoholic steatohepatitis (NASH) patients with type 2 diabetes. Hepatogastroenterology. 2005;52(65):1338–43.
PubMed
Google Scholar
Inui Y, Kawata S, Matsuzawa Y, Tokunaga K, Fujioka S, Tamura S, et al. Inhibitory effect of a new alpha-glucosidase inhibitor on fatty liver in Zucker fatty rats. J Hepatol. 1990;10(1):62–8.
CAS
PubMed
Google Scholar
Nozaki Y, Fujita K, Yoneda M, Wada K, Shinohara Y, Takahashi H, et al. Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease. J Hepatol. 2009;51(3):548–56.
CAS
PubMed
Google Scholar
Rudovich NN, Weickert MO, Machann J, Pfeiffer AF. Combination of acarbose and ezetimibe prevents non-alcoholic fatty liver disease: a break of intestinal insulin resistance? J Hepatol. 2010;52(6):952–3.
PubMed
Google Scholar
Gentile S, Turco S, Guarino G, Oliviero B, Rustici A, Torella R. Non-insulin-dependent diabetes mellitus associated with nonalcoholic liver cirrhosis: an evaluation of treatment with the intestinal alpha-glucosidase inhibitor acarbose. Ann Ital Med Int. 1999;14(1):7–14.
CAS
PubMed
Google Scholar
Monteiro Júnior FD, Silva Júnior WS, Salgado Filho N, Ferreira PAM, Araújo GF, Mandarino NR, et al. Effects of weight loss induced by bariatric surgery on the prevalence of metabolic syndrome. Arq Bras Cardiol. 2009;92(6):418–56.
PubMed
Google Scholar
Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KGMM, Zimmet PZ, et al. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Diabetes Care. 2016;39(6):861–77.
CAS
PubMed
Google Scholar
Cummings DE, Cohen RV. Beyond BMI: the need for new guidelines governing the use of bariatric and metabolic surgery. Lancet Diabetes Endocrinol. 2014;2(2):175–81.
PubMed
PubMed Central
Google Scholar
Clanton J, Subichin M. The effects of metabolic surgery on fatty liver disease and nonalcoholic steatohepatitis. Surg Clin North Am. 2016;96(4):703–15.
PubMed
Google Scholar
Aminian A, Chang J, Brethauer SA, Kim JJ, American Society for Metabolic and Bariatric Surgery Clinical Issues Committee. ASMBS updated position statement on bariatric surgery in class I obesity (BMI 30–35 kg/m2). Surg Obes Relat Dis. 2018;14(8):1071–87.
PubMed
Google Scholar
Berry MA, Urrutia L, Lamoza P, Molina A, Luna E, Parra F, et al. Sleeve gastrectomy outcomes in patients with BMI between 30 and 35–3 years of follow-up. Obes Surg. 2018;28(3):649–55.
PubMed
Google Scholar