From NAFLD to MAFLD and MASLD: a tale of alcohol, stigma and metabolic dysfunction

Abstract

Liver steatosis is a frequent finding in clinical practice and it is estimated to affect 30% of the general adult population worldwide. It became one of the leading causes of end-stage liver disease and hepatocellular carcinoma. From its first description, a diagnosis of nonalcoholic fatty liver disease (NAFLD) required the exclusion of excessive alcohol consumption and concomitant chronic liver diseases of different origins, making it a diagnosis of exclusion. In recent years, the need to stress the strict association between liver steatosis and metabolic dysfunction (i.e., insulin resistance, overweight/obesity, type 2 diabetes, and metabolic syndrome), as well as the desire to define a condition in a positive rather than negative way, led to new definitions and new diagnostic criteria. Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by Eslam et al. in 2020. More recently, a Delphi consensus endorsed by several international hepatologic societies proposed a new terminology [metabolic dysfunction-associated steatotic liver disease (MASLD)] and a new set of diagnostic criteria. The MAFLD and MASLD definitions have a good degree of concordance. They mainly differ in the number of metabolic derangements needed to define “metabolic dysfunction” in normal-weight individuals and in alcohol consumption. Indeed, while MAFLD does not exclude patients with significant alcohol consumption, the recent Delphi consensus included the metabolic dysfunction and alcohol-related liver disease (MetALD) disease entity, a condition in which steatosis, metabolic dysfunction, and moderate alcohol intake coexist. In the present narrative review, we underline the strengths and possible limitations of each definition and summarize available evidence from epidemiologic studies evaluating the clinical usefulness of each set of diagnostic criteria.

Keywords

Nonalcoholic fatty liver disease (NAFLD) / metabolic dysfunction-associated fatty liver disease (MAFLD) / metabolic dysfunction-associated steatotic liver disease (MASLD) / metabolic dysfunction and alcohol-related liver disease(MetALD) / insulin resistance / nomenclature

References

[1] Addison T.Observations on fatty degeneration of the liver.Guy’s Hosp Rep1836;1:485

[2] Ayonrinde OT.Historical narrative from fatty liver in the nineteenth century to contemporary NAFLD - reconciling the present with the past.JHEP Rep2021;3:100261 PMCID:PMC8135048

[3] von Rokitansky K F. A manual of pathological anatomy. Sydenham society;1854. Available from: https://books.google.com/books?hl=zh-CN&lr=&id=06AEAAAAQAAJ&oi=fnd&pg=PR7&dq=+A+manual+of+pathological+anatomy&ots=XIBROfcSFg&sig=I2CoVm53BEMvZgjnm_kZCPfWPBs#v=onepage&q=A%20manual%20of%20pathological%20anatomy&f=false

[4] Budd G. On diseases of the liver. Blanchard and Lea;1853. Available from: https://books.google.com/books?hl=zh-CN&lr=&id=-eE2pRbzF3wC&oi=fnd&pg=PA17&dq=On+diseases+of+the+liver&ots=CYMBQc4BLx&sig=1XuS_DvEPs_t_diX-gPP6-xYI_0#v=onepage&q=On%20diseases%20of%20the%20liver&f=false

[5] Connor CL.Fatty infiltration of the liver and the development of cirrhosis in diabetes and chronic alcoholism.Am J Pathol1938;14:347 PMCID:PMC1964950

[6] Himsworth HP.Discussion: liver damage of metabolic origin.Proceedings of the Royal Society of Medicine1949;42:201-6

[7] Dible JH.Degeneration, necrosis and fibrosis in the liver.Br Med J1951;1:833-41 PMCID:PMC2069069

[8] Ludwig J,McGill DB.Nonalcoholic steatohepatitis: mayo clinic experiences with a hitherto unnamed disease.Mayo Clin Proc1980;55:434-8

[9] Schaffner F.Nonalcoholic fatty liver disease.Prog Liver Dis1986;8:283-98

[10] Lee RG.Nonalcoholic steatohepatitis: a study of 49 patients.Hum Pathol1989;20:594-8

[11] Marchesini G,Morselli-Labate AM.Association of nonalcoholic fatty liver disease with insulin resistance.Am J Med1999;107:450-5

[12] Ciardullo S,Perseghin G.High prevalence of advanced liver fibrosis assessed by transient elastography among U.S. adults with type 2 diabetes.Diabetes Care2021;44:519-25

[13] Ciardullo S,Cannistraci R,Perseghin G.Sex-related association of nonalcoholic fatty liver disease and liver fibrosis with body fat distribution in the general US population.Am J Clin Nutr2022;115:1528-34

[14] Ciardullo S,Grassi G,Perseghin G.Blood pressure, glycemic status and advanced liver fibrosis assessed by transient elastography in the general United States population.J Hypertens2021;39:1621-7 PMCID:PMC9904436

[15] Ciardullo S.Statin use is associated with lower prevalence of advanced liver fibrosis in patients with type 2 diabetes.Metabolism2021;121:154752

[16] Younossi ZM,Younossi Y.Epidemiology of chronic liver diseases in the USA in the past three decades.Gut2020;69:564-8

[17] Younossi ZM,Abdelatif D,Henry L.Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes.Hepatology2016;64:73-84

[18] Younossi ZM,Price JK.The global epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among patients with type 2 diabetes.Clin Gastroenterol Hepatol2024;21:S1542-3565(24)00287

[19] Younossi ZM,de Avila L.The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis.J Hepatol2019;71:793-801

[20] Ciardullo S,Perseghin G.Prevalence of liver steatosis and fibrosis detected by transient elastography in adolescents in the 2017-2018 national health and nutrition examination survey.Clin Gastroenterol Hepatol2021;19:384-390.e1

[21] Ciardullo S,Invernizzi P.Impact of the new definition of metabolic dysfunction-associated fatty liver disease on detection of significant liver fibrosis in US adolescents.Hepatol Commun2022;6:2070-8 PMCID:PMC9315136

[22] Brunt EM,Di Bisceglie AM,Bacon BR.Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.Am J Gastroenterol1999;94:2467-74

[23] Ekstedt M,Nasr P.Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up.Hepatology2015;61:1547-54

[24] Dulai PS,Patel J.Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis.Hepatology2017;65:1557-65 PMCID:PMC5397356

[25] Taylor RS,Bayliss S.Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis.Gastroenterology2020;158:1611-1625.e12

[26] Bucci L,Lenzi B.Italian Liver Cancer GroupThe evolutionary scenario of hepatocellular carcinoma in Italy: an update.Liver Int2017;37:259-70

[27] Piscaglia F,Barchetti A.HCC-NAFLD Italian Study GroupClinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study.Hepatology2016;63:827-38

[28] Perseghin G,Magni S.Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease.Am J Physiol Endocrinol Metab2006;291:E697-703

[29] Valenti LVC.Implications of the evolving knowledge of the genetic architecture of MASLD.Nat Rev Gastroenterol Hepatol2024;21:5-6

[30] Romeo S,Xing C.Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease.Nat Genet2008;40:1461-5 PMCID:PMC2597056

[31] Palmer ND,Yerges-Armstrong LM.Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and Hispanic descent.Hepatology2013;58:966-75 PMCID:PMC3782998

[32] Krawczyk M,Schattenberg JM.NAFLD Clinical Study GroupCombined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study.J Lipid Res2017;58:247-55 PMCID:PMC5234727

[33] Liu YL,Burt AD.TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease.Nat Commun2014;5:4309 PMCID:PMC4279183

[34] Riazi K,Congly SE,Shaheen AA.Race and ethnicity in non-alcoholic fatty liver disease (NAFLD): a narrative review.Nutrients2022;14:4556 PMCID:PMC9658200

[35] Rich NE,Mufti AR.Racial and ethnic disparities in nonalcoholic fatty liver disease prevalence, severity, and outcomes in the united states: a systematic review and meta-analysis.Clin Gastroenterol Hepatol2018;16:198-210.e2 PMCID:PMC5794571

[36] Tovoli F,Mandrioli D.Exploring occupational toxicant exposures in patients with metabolic dysfunction-associated steatotic liver disease: a prospective pilot study.Dig Liver Dis2024;56:571-8

[37] Polyzos SA,Deretzi G,Mantzoros CS.The emerging role of endocrine disruptors in pathogenesis of insulin resistance: a concept implicating nonalcoholic fatty liver disease.Curr Mol Med2012;12:68-82

[38] Cheng WC,Wu CD,Lee PC.Non-linear association between long-term air pollution exposure and risk of metabolic dysfunction-associated steatotic liver disease.Environ Health Prev Med2024;29:7 PMCID:PMC10898959

[39] Byrne CD.NAFLD: a multisystem disease.J Hepatol2015;62:S47-64

[40] Mantovani A,Beatrice G,Byrne CD.Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals.Gut2021;70:962-9

[41] Mantovani A,Byrne CD.Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis.Metabolism2018;79:64-76

[42] Ciardullo S,Trevisan R.Liver fibrosis assessed by transient elastography is independently associated with albuminuria in the general United States population.Dig Liver Dis2021;53:866-72

[43] Mantovani A,Beatrice G.Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies.Gut2022;71:778-88

[44] Shedlock K,Gorman GH,Erdie-Lalena CR.Autism spectrum disorders and metabolic complications of obesity.J Pediatr2016;178:183-187.e1

[45] Hydes TJ,Glyn-Owen K.Liver fibrosis assessed via noninvasive tests is associated with incident heart failure in a general population cohort.Clin Gastroenterol Hepatol2024;22:1657-67

[46] Kasper P,Lang S.NAFLD and cardiovascular diseases: a clinical review.Clin Res Cardiol2021;110:921-37 PMCID:PMC8238775

[47] Ciardullo S,Rea F,Perseghin G.Time trends in liver-related mortality in people with and without diabetes: results from a population based study.J Clin Endocrinol Metab2024;20:dgae182

[48] Younossi ZM,Ong J.Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in the United States.Clin Gastroenterol Hepatol2021;19:580-589.e5

[49] Karlsen TH,Zelber-Sagi S.The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality.Lancet2022;399:61-116

[50] Israelsen M,Detlefsen S.GALAXY and MicrobLiver consortiakMetabolic and genetic risk factors are the strongest predictors of severity of alcohol-related liver fibrosis.Clin Gastroenterol Hepatol2022;20:1784-1794.e9

[51] Kim HS,Byun J.Synergistic Associations of PNPLA3 I148M Variant, Alcohol intake, and obesity with risk of cirrhosis, hepatocellular carcinoma, and mortality.JAMA Netw Open2022;5:e2234221 PMCID:PMC9530967

[52] World Health Organization. Global status report on alcohol and health 2018. Available from: https://www.who.int/publications/i/item/9789241565639[DOI:10.4324/9780203029732-13

[53] Griswold M G,Hawley C.Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet2018;392:1015-35 PMCID:PMC8776563

[54] 2020 Alcohol Collaborators. Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the global burden of disease study 2020.Lancet2022;400:185-235. PMCID:PMC9289789

[55] Sehrawat TS,Liu M.Circulating extracellular vesicles carrying sphingolipid cargo for the diagnosis and dynamic risk profiling of alcoholic hepatitis.Hepatology2021;73:571-85 PMCID:PMC7541595

[56] Nasr P,Ekstedt M.Misclassified alcohol-related liver disease is common in presumed metabolic dysfunction-associated steatotic liver disease and highly increases risk for future cirrhosis.Clin Gastroenterol Hepatol2024;22:1048-1057.e2

[57] Conigrave KM,Reznik RB.Predictive capacity of the AUDIT questionnaire for alcohol-related harm.Addiction1995;90:1479-85

[58] Staufer K,Strebinger G.Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease.J Hepatol2022;77:918-30

[59] Kintz P.2014 consensus for the use of alcohol markers in hair for assessment of both abstinence and chronic excessive alcohol consumption.Forensic Sci Int2015;249:A1-2

[60] Room R.Stigma, social inequality and alcohol and drug use.Drug Alcohol Rev2005;24:143-55

[61] Schomerus G,Holzinger A,Carta MG.The stigma of alcohol dependence compared with other mental disorders: a review of population studies.Alcohol Alcohol2011;46:105-12

[62] Younossi ZM,Alswat K.Global NASH CouncilGlobal survey of stigma among physicians and patients with nonalcoholic fatty liver disease.J Hepatol2024;80:419-30

[63] Lonardo A,Caldwell SH.Researchers call for more flexible editorial conduct rather than abruptly adopting only the new MASLD nomenclature.J Hepatol2024;80:e192-4

[64] Leoni S,Napoli L,Ferri S.Current guidelines for the management of non-alcoholic fatty liver disease: a systematic review with comparative analysis.World J Gastroenterol2018;24:3361-73 PMCID:PMC6092580

[65] 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 Hepatol2016;64:1388-402 PMCID:PMC5644799

[66] Glen J,Day C.Guideline Development GroupNon-alcoholic fatty liver disease (NAFLD): summary of NICE guidance.BMJ2016;354:i4428

[67] Wong VW,Chitturi S.Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 1: Definition, risk factors and assessment.J Gastroenterol Hepatol2018;33:70-85

[68] Association for the Study of the Liver (AISF). AISF position paper on nonalcoholic fatty liver disease (NAFLD): updates and future directions.Dig Liver Dis2017;49:471-83

[69] Eslam M,Sarin SK.A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.J Hepatol2020;73:202-9

[70] Rinella ME,Ratziu V.NAFLD Nomenclature consensus groupA multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann Hepatol2024;29:101133 PMCID:PMC10653297

[71] Yamamura S,Kawaguchi T.MAFLD identifies patients with significant hepatic fibrosis better than NAFLD.Liver Int2020;40:3018-30

[72] Lin S,Wang M.Comparison of MAFLD and NAFLD diagnostic criteria in real world.Liver Int2020;40:2082-9

[73] Ciardullo S.Prevalence of NAFLD, MAFLD and associated advanced fibrosis in the contemporary United States population.Liver Int2021;41:1290-3

[74] Hagström H,Ekstedt M.99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical.J Hepatol2024;80:e76-7

[75] Ratziu V.AFEF Group for the Study of Liver FibrosisConfirmatory biomarker diagnostic studies are not needed when transitioning from NAFLD to MASLD.J Hepatol2024;80:e51-2

[76] Perseghin G.Exploring the in vivo mechanisms of action of glucokinase activators in type 2 diabetes.J Clin Endocrinol Metab2010;95:4871-3

[77] Lee CM,Kim M.Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings.Hepatology2024;79:1393-400

[78] Lee BP,Terrault NA.National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature.Hepatology24;79:666-73. PMCID:PMC11232657

[79] Israelsen M,Johansen S.GALAXY consortiumValidation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study.Lancet Gastroenterol Hepatol2024;9:218-28

[80] Israelsen M,Johansen S,Krag A.MetALD: new opportunities to understand the role of alcohol in steatotic liver disease.Lancet Gastroenterol Hepatol2023;8:866-8

[81] Choe HJ,Kim W,Cho NH.Steatotic liver disease predicts cardiovascular disease and advanced liver fibrosis: a community-dwelling cohort study with 20-year follow-up.Metabolism2024;153:155800

[82] Han E,Kang ES.Mortality in metabolic dysfunction-associated steatotic liver disease: a nationwide population-based cohort study.Metabolism2024;152:155789

[83] Kim D,Cholankeril G.Metabolic dysfunction-associated steatotic liver disease and all-cause/cause-specific mortality among adults in the United States.J Hepatol2024;80:e79-81

[84] Lee HH,Kim EJ.Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease.Gut2024;73:533-40

[85] Ciardullo S,Morieri ML,Invernizzi P.Impact of MASLD and MetALD on clinical outcomes: a meta-analysis of preliminary evidence.Liver Int2024;44:1762-7

[86] Ramírez-Mejía MM,Eslam M,Méndez-Sánchez N.Breaking new ground: MASLD vs. MAFLD-which holds the key for risk stratification?.Hepatol Int2024;18:168-78

[87] De A,Mehta M,Duseja A.Metabolic dysfunction-associated steatotic liver disease (MASLD) definition is better than MAFLD criteria for lean patients with NAFLD.J Hepatol2024;80:e61-2

[88] Pan Z,Esmat G,Eslam M.MAFLD predicts cardiovascular disease risk better than MASLD.Liver Int2024;44:1567-74

[89] Byrne CD.MASLD, MAFLD, or NAFLD criteria: have we re-created the confusion and acrimony surrounding Metabolic syndrome?.Metab Target Organ Damage2024;4:10

[90] Reaven GM.Role of insulin resistance in human disease.Diabetes1988;37:1595-607

[91] National Cholesterol Education Program (US); Expert Panel On Detection, Treatment Of High Blood Cholesterol In Adults. Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III). The Program, 2002. Available from: https://books.google.com/books?hl=zh-CN&lr=&id=VKpLAQAAIAAJ&oi=fnd&pg=PR2&dq=Third+report+of+the+national+cholesterol+education+program+(NCEP)+expert+panel+on+detection,+evaluation,+and+treatment+of+high+blood+cholesterol+in+adults&ots=jXkq2nMHhu&sig=07y2oicjyvSXt6TpFIho3hc-lSM#v=onepage&q=Third%20report%20of%20the%20national%20cholesterol%20education%20program%20(NCEP)%20expert%20panel%20on%20detection%2C%20evaluation%2C%20and%20treatment%20of%20high%20blood%20cholesterol%20in%20adults&f=false

[92] Alberti ,Eckel ,Grundy SM et al.Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity.Circulation2009;120:1640-5

[93] DeFronzo RA.Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease.Diabetes Care1991;14:173-94

[94] DeFronzo RA,Andres R.Glucose clamp technique: a method for quantifying insulin secretion and resistance.Am J Physiol1979;237:E214-23

[95] Matthews DR,Rudenski AS,Treacher DF.Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia1985;28:412-9

[96] Perseghin G,Caloni M,Luzi L.Incorporation of the fasting plasma FFA concentration into QUICKI improves its association with insulin sensitivity in nonobese individuals.J Clin Endocrinol Metab2001;86:4776-81

[97] Katz A,Mather K.Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.J Clin Endocrinol Metab2000;85:2402-10

[98] Ciardullo S,Lepore G.Development of a new model of insulin sensitivity in patients with type 2 diabetes and association with mortality.J Clin Endocrinol Metab2024;109:1308-17

[99] Bonora E,Alberiche M.Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity.Diabetes Care2000;23:57-63

[100] Tohidi M,Ghasemi A.Assay-dependent variability of serum insulin concentrations: a comparison of eight assays.Scand J Clin Lab Invest2017;77:122-9

[101] Guzder RN,Mullee MA.Impact of metabolic syndrome criteria on cardiovascular disease risk in people with newly diagnosed type 2 diabetes.Diabetologia2006;49:49-55

[102] Shang Y,Modica A.Metabolic syndrome traits increase the risk of major adverse liver outcomes in type 2 diabetes.Diabetes Care2024;47:978-85 PMCID:PMC11116921

[103] Asghar A.Role of immune cells in obesity induced low grade inflammation and insulin resistance.Cell Immunol2017;315:18-26

[104] Park H,Kim M,Nah EH.Nomenclature dilemma of metabolic associated fatty liver disease (MAFLD): considerable proportions of mafld are metabolic healthy.Clin Gastroenterol Hepatol2023;21:1041-1049.e3

[105] Stefan N.Metabolically healthy and unhealthy normal weight and obesity.Endocrinol Metab (Seoul)2020;35:487-93 PMCID:PMC7520592

[106] Hrasko T,Hainer V.Metabolically healthy obese individuals - mechanisms and clinical relevance.Cesk Fysiol2016;65:38-46

[107] Calori G,Piemonti L.Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the cremona study.Diabetes Care2011;34:210-5 PMCID:PMC3005463

[108] Flegal KM,Orpana H.Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis.JAMA2013;309:71-82 PMCID:PMC4855514

[109] Gruberg L,Waksman R.The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox?.J Am Coll Cardiol2002;39:578-84

[110] Hainer V.Obesity paradox does exist.Diabetes Care2013;36 Suppl 2:S276-81 PMCID:PMC3920805

[111] Global BMI Mortality Collaboration,Bhupathiraju ShN.Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents.Lancet2016;388:776-86. PMCID:PMC4995441

[112] Blüher M.Metabolically healthy obesity.Endocr Rev2020;41:bnaa004 PMCID:PMC7098708

[113] Mongraw-Chaffin M,Anderson CAM.Metabolically healthy obesity, transition to metabolic syndrome, and cardiovascular risk.J Am Coll Cardiol2018;71:1857-65 PMCID:PMC6002856

[114] Singh A,Singh S.Awareness of nonalcoholic fatty liver disease is increasing but remains very low in a representative us cohort.Dig Dis Sci2020;65:978-86

[115] Marchesini G,Bianchi G.Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.Diabetes2001;50:1844-50