Top

Hepatology International

Published in:

Open Access 09-08-2023 | Fatty Liver | Review Article

Current understanding and future perspectives on the impact of changing NAFLD to MAFLD on global epidemiology and clinical outcomes

Authors: Karl Vaz, Daniel Clayton-Chubb, Ammar Majeed, John Lubel, David Simmons, William Kemp, Stuart K. Roberts

Published in: Hepatology International | Issue 5/2023

Abstract

Introduction

For the first time in nearly half a century, fatty liver disease has undergone a change in name and definition, from the exclusive term, non-alcoholic fatty liver disease (NAFLD), to the inclusion-based, metabolic-associated fatty liver disease (MAFLD). This has led investigators across the globe to evaluate the impact the nomenclature change has had on the epidemiology and natural history of the disease.

Methods

This systematic review provides a comprehensive overview on how the shift in name and diagnostic criteria has influenced point prevalence in different geographic regions, as well as morbidity and mortality risk, whilst highlighting gaps in the literature that need to be addressed.

Conclusions

MAFLD prevalence is higher than NAFLD prevalence, carries a higher risk of overall mortality, with greater granularity in risk-stratification amongst MAFLD subtypes.

Graphical abstract

Available only for authorised users

Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55(7):434–438PubMed

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(1):73–84PubMedCrossRef

Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: disease burden, current management and future challenges. JHEP Rep 2020;2(6): 100192PubMedPubMedCentralCrossRef

Wong RJ, Singal AK. Trends in liver disease etiology among adults awaiting liver transplantation in the United States, 2014–2019. JAMA Netw Open 2020;3(2): e1920294PubMedCrossRef

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):202–209PubMedCrossRef

Eslam M, Sanyal AJ, George J, International Consensus P. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020;158(7):1999-2014.e1CrossRef

European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016;64(6):1388–402CrossRef

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(1):328–357PubMedCrossRef

Younossi ZM, Rinella ME, Sanyal AJ, Harrison SA, Brunt EM, Goodman Z, et al. From NAFLD to MAFLD: implications of a premature change in terminology. Hepatology 2021;73(3):1194–1198PubMedCrossRef

10.

Singh SP, Anirvan P, Reddy KR, Conjeevaram HS, Marchesini G, Rinella ME, et al. Non-alcoholic fatty liver disease: Not time for an obituary just yet! J Hepatol 2021;74(4):972–974PubMedCrossRef

11.

Ratziu V, Rinella M, Beuers U, Loomba R, Anstee QM, Harrison S, et al. The times they are a-changin’ (for NAFLD as well). J Hepatol 2020;73(6):1307–1309PubMedCrossRef

12.

Eslam M, Sarin SK, Wong VW, Fan JG, Kawaguchi T, Ahn SH, et al. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol Int 2020;14(6):889–919PubMedCrossRef

13.

AASLD. Reaching Consensus on NAFLD Nomenclature 2022 [Available from: https://www.aasld.org/news/reaching-consensus-nafld-nomenclature.

14.

EASL. NAFLD Nomenclature Consensus Meeting High-Level Output 2022 [Available from: https://easl.eu/news/nafld-nomenclature-consensus-meeting-high-level-output/.

15.

Lin S, Huang J, Wang M, Kumar R, Liu Y, Liu S, et al. Comparison of MAFLD and NAFLD diagnostic criteria in real world. Liver Int 2020;40(9):2082–2089PubMedCrossRef

16.

Zhang P, Dong X, Zhang W, Wang S, Chen C, Tang J, et al. Metabolic-associated fatty liver disease and the risk of cardiovascular disease. Clin Res Hepatol Gastroenterol 2023;47(1): 102063PubMedCrossRef

17.

Huang Q, Zou X, Wen X, Zhou X, Ji L. NAFLD or MAFLD: which has closer association with all-cause and cause-specific mortality?-Results from NHANES III. Front Med (Lausanne) 2021;8: 693507PubMedCrossRef

18.

Paik J, Golabi P, Younoszai Z, Mishra A, Trimble G, Younossi ZM. Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease. Liver Int 2019;39(2):342–352PubMedCrossRef

19.

Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol 2012;10(6):646–650PubMedCrossRef

20.

Lazo M, Hernaez R, Bonekamp S, Kamel IR, Brancati FL, Guallar E, et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011;343: d6891PubMedPubMedCentralCrossRef

21.

Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol 2013;178(1):38–45PubMedPubMedCentralCrossRef

22.

Nguyen VH, Le MH, Cheung RC, Nguyen MH. Differential clinical characteristics and mortality outcomes in persons With NAFLD and/or MAFLD. Clin Gastroenterol Hepatol 2021;19(10):2172–81 e6PubMedCrossRef

23.

Aimuzi R, Xie Z, Qu Y, Jiang Y, Luo K. Associations of urinary organophosphate esters metabolites and diet quality with nonalcoholic/metabolic dysfunction-associated fatty liver diseases in adults. Ecotoxicol Environ Saf 2023;254: 114720PubMedCrossRef

24.

Ciardullo S, Perseghin G. Prevalence of NAFLD, MAFLD and associated advanced fibrosis in the contemporary United States population. Liver Int 2021;41(6):1290–1293PubMedCrossRef

25.

Xie ZQ, Li HX, Tan WL, Yang L, Ma XW, Li WX, et al. Association of serum vitamin C With NAFLD and MAFLD among adults in the United States. Front Nutr 2021;8: 795391PubMedCrossRef

26.

Wong RJ, Cheung R. Trends in the prevalence of metabolic dysfunction-associated fatty liver disease in the United States, 2011–2018. Clin Gastroenterol Hepatol 2022;20(3):e610–e613PubMedCrossRef

27.

Zhang HJ, Wang YY, Chen C, Lu YL, Wang NJ. Cardiovascular and renal burdens of metabolic associated fatty liver disease from serial US national surveys, 1999–2016. Chin Med J (Engl) 2021;134(13):1593–1601PubMedCrossRef

28.

Xu X, Zhou X, Tian T, Ding Y, Yu C, Zhao W, et al. Comparison of clinical characteristics and outcomes of MAFLD and NAFLD in Chinese Health examination populations. J Clin Transl Hepatol 2023;11(4):777–786PubMedPubMedCentral

29.

Wang X, Wu S, Yuan X, Chen S, Fu Q, Sun Y, et al. Metabolic dysfunction-associated fatty liver disease and mortality among chinese adults: a prospective cohort study. J Clin Endocrinol Metab 2022;107(2):e745–e755PubMedCrossRef

30.

Liang Y, Chen H, Liu Y, Hou X, Wei L, Bao Y, et al. Association of MAFLD with diabetes, chronic kidney disease, and cardiovascular disease: a 4.6-year cohort study in China. J Clin Endocrinol Metab 2022;107(1):88–97PubMedCrossRef

31.

Yu C, Wang M, Zheng S, Xia M, Yang H, Zhang D, et al. Comparing the diagnostic criteria of MAFLD and NAFLD in the Chinese population: a population-based prospective cohort study. J Clin Transl Hepatol 2022;10(1):6–16PubMedCrossRef

32.

Liu Q, Zhao G, Li Q, Wu W, Zhang Y, Bian H. A comparison of NAFLD and MAFLD diagnostic criteria in contemporary urban healthy adults in China: a cross-sectional study. BMC Gastroenterol 2022;22(1):471PubMedPubMedCentralCrossRef

33.

Miao L, Yang L, Guo LS, Shi QQ, Zhou TF, Chen Y, et al. Metabolic dysfunction-associated fatty liver disease is associated with greater impairment of lung function than nonalcoholic fatty liver disease. J Clin Transl Hepatol 2022;10(2):230–237PubMedPubMedCentralCrossRef

34.

Wang Y, Yu Y, Zhang H, Chen C, Wan H, Chen Y, et al. Cardiovascular and renal burdens among patients with MAFLD and NAFLD in China. Front Endocrinol (Lausanne) 2022;13: 968766PubMedCrossRef

35.

Yuan X, Wang X, Wu S, Chen S, Wang Y, Wang J, Lu Y, Sun Y, Fu Q, Wang L. Associations between metabolic dysfunction-associated fatty liver disease and extrahepatic cancers: a cohort in China. HepatoBiliary Surg Nutr 2022. https://hbsn.amegroups.org/article/view/96588/pdf

36.

Zeng J, Qin L, Jin Q, Yang RX, Ning G, Su Q, et al. Prevalence and characteristics of MAFLD in Chinese adults aged 40 years or older: a community-based study. Hepatobiliary Pancreat Dis Int 2022;21(2):154–161PubMedCrossRef

37.

Wong VW, Wong GL, Woo J, Abrigo JM, Chan CK, Shu SS, et al. Impact of the new definition of metabolic associated fatty liver disease on the epidemiology of the disease. Clin Gastroenterol Hepatol 2021;19(10):2161–71.e5PubMedCrossRef

38.

Cheng YM, Wang CC, Kao JH. Metabolic associated fatty liver disease better identifying patients at risk of liver and cardiovascular complications. Hepatol Int 2023;17(2):350–356PubMedCrossRef

39.

Lee H, Lee YH, Kim SU, Kim HC. Metabolic Dysfunction-Associated Fatty Liver Disease and Incident Cardiovascular Disease Risk: A Nationwide Cohort Study. Clin Gastroenterol Hepatol 2021;19(10):2138–47.e10PubMedCrossRef

40.

Chun HS, Lee M, Lee JS, Lee HW, Kim BK, Park JY, et al. Metabolic dysfunction associated fatty liver disease identifies subjects with cardiovascular risk better than non-alcoholic fatty liver disease. Liver Int 2022. https://pubmed.ncbi.nlm.nih.gov/36585250/

41.

Choi JM, Park HE, Han YM, Lee J, Lee H, Chung SJ, et al. Non-alcoholic/metabolic-associated fatty liver disease and helicobacter pylori additively increase the risk of arterial stiffness. Front Med (Lausanne) 2022;9: 844954PubMedCrossRef

42.

Kim H, Lee CJ, Ahn SH, Lee KS, Lee BK, Baik SJ, et al. MAFLD predicts the risk of cardiovascular disease better than NAFLD in asymptomatic subjects with health check-ups. Dig Dis Sci 2022;67(10):4919–4928PubMedCrossRef

43.

Kim KS, Hong S, Ahn HY, Park CY. Metabolic dysfunction-associated fatty liver disease and mortality: a population-based cohort study. Diabetes Metab J 2023. https://doi.org/10.4093/dmj.2021.0327CrossRefPubMedPubMedCentral

44.

Seo JY, Bae JH, Kwak MS, Yang JI, Chung SJ, Yim JY, et al. The risk of colorectal adenoma in nonalcoholic or metabolic-associated fatty liver disease. Biomedicines 2021;9(10):1401PubMedPubMedCentralCrossRef

45.

Yoo TK, Lee MY, Kim SH, Zheng MH, Targher G, Byrne CD, et al. Comparison of cardiovascular mortality between MAFLD and NAFLD: a cohort study. Nutr Metab Cardiovasc Dis 2023;33(5):947–955PubMedCrossRef

46.

Fujii H, Fukumoto S, Enomoto M, Uchida-Kobayashi S, Kimura T, Tamori A, et al. The FibroScan-aspartate aminotransferase score can stratify the disease severity in a Japanese cohort with fatty liver diseases. Sci Rep 2021;11(1):13844PubMedPubMedCentralCrossRef

47.

Bessho R, Kashiwagi K, Ikura A, Yamataka K, Inaishi J, Takaishi H, et al. A significant risk of metabolic dysfunction-associated fatty liver disease plus diabetes on subclinical atherosclerosis. PLoS One 2022;17(5): e0269265PubMedPubMedCentralCrossRef

48.

Tateda T, Iino C, Sasada T, Sato S, Igarashi G, Kawaguchi S, et al. Evaluation of metabolic dysfunction-associated fatty liver disease using FibroScan, diet, and microbiota: a large cross-sectional study. PLoS One 2022;17(11): e0277930PubMedPubMedCentralCrossRef

49.

Sogabe M, Okahisa T, Kurihara T, Kagawa M, Ueda H, Kawaguchi T, et al. Comparison of the role of alcohol consumption and qualitative abdominal fat on NAFLD and MAFLD in males and females. Sci Rep 2022;12(1):16048PubMedPubMedCentralCrossRef

50.

Tanaka M, Mori K, Takahashi S, Higashiura Y, Ohnishi H, Hanawa N, et al. Metabolic dysfunction-associated fatty liver disease predicts new onset of chronic kidney disease better than fatty liver or nonalcoholic fatty liver disease. Nephrol Dial Transplant 2023;38(3):700–711PubMedCrossRef

51.

Mori K, Tanaka M, Hosaka I, Mikami T, Endo K, Hanawa N, et al. Metabolic dysfunction-associated fatty liver disease is associated with an increase in systolic blood pressure over time: linear mixed-effects model analyses. Hypertens Res 2023;46(5):1110–1121PubMedCrossRef

52.

Niriella MA, Ediriweera DS, Kasturiratne A, De Silva ST, Dassanayaka AS, De Silva AP, et al. Outcomes of NAFLD and MAFLD: results from a community-based, prospective cohort study. PLoS One 2021;16(2): e0245762PubMedPubMedCentralCrossRef

53.

Kemp W, Clayton-Chubb D, Majeed A, Glenister KM, Magliano DJ, Lubel J, et al. Impact of renaming NAFLD to MAFLD in an Australian regional cohort: Results from a prospective population-based study. J Gastroenterol Hepatol 2022;37(2):395–403PubMedCrossRef

54.

van Kleef LA, Ayada I, Alferink LJM, Pan Q, de Knegt RJ. Metabolic dysfunction-associated fatty liver disease improves detection of high liver stiffness: the Rotterdam Study. Hepatology 2022;75(2):419–429PubMedCrossRef

55.

Kim D, Konyn P, Sandhu KK, Dennis BB, Cheung AC, Ahmed A. Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States. J Hepatol 2021;75(6):1284–1291PubMedCrossRef

56.

Younossi ZM, Paik JM, Al Shabeeb R, Golabi P, Younossi I, Henry L. Are there outcome differences between NAFLD and metabolic-associated fatty liver disease? Hepatology 2022;76(5):1423–1437PubMedCrossRef

57.

Zhang YC, Lyu ZY, Ma B, Li LM, Wang W, Sheng C, et al. A new risk stratification strategy for fatty liver disease by incorporating MAFLD and fibrosis score in a large US population. Hepatol Int 2022;16(4):835–845PubMedCrossRef

58.

Moon JH, Kim W, Koo BK, Cho NH, Innovative Target Exploration of Nc. Metabolic dysfunction-associated fatty liver disease predicts long-term mortality and cardiovascular disease. Gut Liver 2022;16(3):433–42PubMedCrossRef

59.

Yoneda M, Yamamoto T, Honda Y, Imajo K, Ogawa Y, Kessoku T, et al. Risk of cardiovascular disease in patients with fatty liver disease as defined from the metabolic dysfunction associated fatty liver disease or nonalcoholic fatty liver disease point of view: a retrospective nationwide claims database study in Japan. J Gastroenterol 2021;56(11):1022–1032PubMedPubMedCentralCrossRef

60.

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(2):372–382PubMedCrossRef

61.

Mantovani A, Petracca G, Beatrice G, Csermely A, Lonardo A, Schattenberg JM, et al. Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis. Gut 2022;71(1):156–162PubMedCrossRef

62.

Mantovani A, Petracca G, Beatrice G, Csermely A, Tilg H, Byrne CD, et al. Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies. Gut 2022;71(4):778–788PubMedCrossRef

63.

Mantovani A, Petracca G, Beatrice G, Tilg H, Byrne CD, Targher G. Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals. Gut 2021;70(5):962–969PubMedCrossRef

64.

Mantovani A, Zaza G, Byrne CD, Lonardo A, Zoppini G, Bonora E, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis. Metabolism 2018;79:64–76PubMedCrossRef

65.

Musso G, Gambino R, Tabibian JH, Ekstedt M, Kechagias S, Hamaguchi M, et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med 2014;11(7): e1001680PubMedPubMedCentralCrossRef

66.

Orci LA, Sanduzzi-Zamparelli M, Caballol B, Sapena V, Colucci N, Torres F, et al. Incidence of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. Clin Gastroenterol Hepatol 2022;20(2):283–92 e10PubMedCrossRef

67.

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(3):589–600PubMedCrossRef

68.

Lee H, Lee HW, Kim SU, Chang KH. Metabolic dysfunction-associated fatty liver disease increases colon cancer risk: a nationwide cohort study. Clin Transl Gastroenterol 2022;13(1): e00435PubMedPubMedCentralCrossRef

69.

Myers S, Neyroud-Caspar I, Spahr L, Gkouvatsos K, Fournier E, Giostra E, et al. NAFLD and MAFLD as emerging causes of HCC: a populational study. JHEP Rep 2021;3(2): 100231PubMedPubMedCentralCrossRef

Title: Current understanding and future perspectives on the impact of changing NAFLD to MAFLD on global epidemiology and clinical outcomes
Authors: Karl Vaz
Daniel Clayton-Chubb
Ammar Majeed
John Lubel
David Simmons
William Kemp
Stuart K. Roberts
Publication date: 09-08-2023
Publisher: Springer India
Keywords: Fatty Liver
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: Hepatology International / Issue 5/2023
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-023-10568-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

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

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

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

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Conclusions

Graphical abstract

Please log in to get access to this content

Other articles of this Issue 5/2023

Laparoscopic and open liver resection for hepatocellular carcinoma with type 2 diabetes mellitus: multicenter propensity score-matched study

Prospects for treatment of esophageal varices considering the safety of endoscopic band ligation

Correction to: Serum interleukin-6 level predicts the prognosis for patients with alcohol-related acute-on-chronic liver failure

High-potency nucleos(t)ide analogues alone or plus immunoglobulin for HBV prophylaxis after liver transplantation: a meta-analysis

Synthetic miR-26a mimics delivered by tumor exosomes repress hepatocellular carcinoma through downregulating lymphoid enhancer factor 1

Liver fibrosis quantified by image morphometry predicts clinical outcomes in patients with non-alcoholic fatty liver disease

Keynote webinar | Spotlight on medication adherence

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

At a glance: The STEP trials