Yet more evidence that MAFLD is more than a name change

Abstract

In their elegant study in 4,653 Chinese patients, Xia et al.[1]Xia M.Z.H. Wang S. Tang H. Gao X. Insights into contribution of genetic variants towards the susceptibility of MAFLD revealed by the NMR_based lipoprotein profiling.J Hepatol. 2021; 74: 974-977Abstract Full Text Full Text PDF Scopus (10) Google Scholar provide robust evidence that the presence of metabolic dysfunction, including but not limited to adiposity, is a prerequisite for the deleterious impacts of the PNPLA3 rs738409 and TM6SF2 rs58542926 risk alleles on hepatic steatosis and lipoprotein profiles. They conclude that the MAFLD definition has dual advantages compared to the old NAFLD definition: i) it better captures the population who would benefit from an evaluation of genetic risks for fatty liver and ii) it overcomes the issue that the role of the variants was easy to neglect in those with alcoholic fatty liver disease/viral hepatitis etc., under the NAFLD definition. This and other reports add to mounting evidence demonstrating the superiority of the MAFLD criteria for identifying patients at high-risk of hepatic and extrahepatic complications, emphasising that the re-definition extends far beyond a mere name change.2Yamamura S. Eslam M. Kawaguchi T. Tsutsumi T. Nakano D. Yoshinaga S. et al.MAFLD identifies patients with significant hepatic fibrosis better than NAFLD.Liver Int. 2020 Sep 30; (Online ahead of print)https://doi.org/10.1111/liv.14675Crossref PubMed Scopus (89) Google Scholar, 3Lin 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 Sep; 40: 2082-2089Crossref PubMed Scopus (132) Google Scholar, 4Mak L.-Y. Yuen M.-F. Seto W.-K. Letter regarding “A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement”.J Hepatol. 2020 Dec; 73: 1573-1574Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 5Sun D.-Q. Jin Y. Wang T.-Y. Zheng K.I. Rios R.S. Zhang H.-Y. et al.MAFLD and risk of CKD.Metabolism. 2020; : 154433PubMed Google Scholar, 6Eslam M. George J. Reply to: correspondence regarding "A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement": bringing evidence to the NAFLD-MAFLD debate.J Hepatol. 2020; 73: 1575Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 7Fouad Y. Elwakil R. Elsahhar M. Said E. Bazeed S. Gomaa A.A. et al.The NAFLD-MAFLD debate: eminence versus evidence.Liver Int. 2021 Feb; 41: 255-260Crossref PubMed Scopus (29) Google Scholar, 8Lee Y.-H. Kim S.U. Kim H.C. Metabolic dysfunction-associated fatty liver disease and incident cardiovascular disease risk: a nationwide cohort study.Clin Gastroenterol H. 2020 Dec 22; (S1542-3565(20)31717-1)Abstract Full Text Full Text PDF Scopus (31) Google Scholar Singh et al.[9]Singh S.P. Anirvan P. Reddy K.R. Conjeevaram H.S. Marchesini G. Rinella M.E. et al.Non-alcoholic fatty liver disease: not time for an obituary just yet!.J Hepatol. 2021; 74: 972-974Abstract Full Text Full Text PDF Scopus (11) Google Scholar have some comments on our work[10]Eslam M. Newsome P.N. Sarin S.K. Anstee Q.M. 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: 202-209Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar,[11]Eslam M. Sanyal A.J. George J. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.Gastroenterology. 2020 May; 158 (1999-2014.e1)Abstract Full Text Full Text PDF PubMed Scopus (634) Google Scholar to which we would like to respond. The authors argue in favour of a name and a diagnosis of exclusion (NAFLD), stating that in medicine, this has been practiced since time immemorial. This is right in many instances when the pathophysiological basis of a disease is unknown when first described, but once clarified, a change is needed. The change from “non-A, non-B” to hepatitis C is an exemplar.[12]Pawlotsky J.-M. Feld J.J. Zeuzem S. Hoofnagle J.H. From non-A, non-B hepatitis to hepatitis C virus cure.J Hepatol. 2015; 62: S87-S99Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar Interestingly, the article by Dr. Reuben from 2002 that they refer too[13]Reuben A. Leave gourmandising.Hepatology. 2002; 36: 1303-1306Crossref PubMed Scopus (10) Google Scholar stated that while “nonalcoholic fatty liver disease” – and its acronyms NAFL and NAFLD – “encompasses all possible histologic forms of the syndrome” it does not “articulate well… and sounds more like military terms for a blunder than a liver disease”! Yet, despite these very early caveats and repeated acknowledgement of the same, clinical inertia has impeded and stymied the correction process. After 4 decades, hepatology would be ill served by further delays, particularly as MAFLD more accurately reflects current understanding of pathophysiology, and cold hard scientific evidence (rather than opinion) can be brought to bear on the debate.[7]Fouad Y. Elwakil R. Elsahhar M. Said E. Bazeed S. Gomaa A.A. et al.The NAFLD-MAFLD debate: eminence versus evidence.Liver Int. 2021 Feb; 41: 255-260Crossref PubMed Scopus (29) Google Scholar Simply put, a diagnosis by exclusion is a diagnosis with “no means of objective proof”.[14]Fred H.L. The diagnosis of exclusion: an ongoing uncertainty.Tex Heart Inst J. 2013; 40: 379PubMed Google Scholar This lack of “objective proof” implicitly brings heterogeneity, which consequently impedes the development of rational, evidence-based therapies. The approach brings confusion, resulting in increased healthcare costs, wastage of time and acts as a barrier to effective care.[15]Spiegel B.M. Farid M. Esrailian E. Talley J. Chang L. Is irritable bowel syndrome a diagnosis of exclusion?: a survey of primary care providers, gastroenterologists, and IBS experts.The Am J Gastroenterol. 2010; 105: 848Crossref PubMed Scopus (127) Google Scholar This is what we see in “NAFLD” with clinical trials increasingly attempting to correct for tremendous variability in disease progression by only including individuals with advanced histological forms of the disease. In contrast, MAFLD identifies patients with advanced fibrosis and metabolic risk.2Yamamura S. Eslam M. Kawaguchi T. Tsutsumi T. Nakano D. Yoshinaga S. et al.MAFLD identifies patients with significant hepatic fibrosis better than NAFLD.Liver Int. 2020 Sep 30; (Online ahead of print)https://doi.org/10.1111/liv.14675Crossref PubMed Scopus (89) Google Scholar, 3Lin 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 Sep; 40: 2082-2089Crossref PubMed Scopus (132) Google Scholar, 4Mak L.-Y. Yuen M.-F. Seto W.-K. Letter regarding “A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement”.J Hepatol. 2020 Dec; 73: 1573-1574Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 5Sun D.-Q. Jin Y. Wang T.-Y. Zheng K.I. Rios R.S. Zhang H.-Y. et al.MAFLD and risk of CKD.Metabolism. 2020; : 154433PubMed Google Scholar, 6Eslam M. George J. Reply to: correspondence regarding "A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement": bringing evidence to the NAFLD-MAFLD debate.J Hepatol. 2020; 73: 1575Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 7Fouad Y. Elwakil R. Elsahhar M. Said E. Bazeed S. Gomaa A.A. et al.The NAFLD-MAFLD debate: eminence versus evidence.Liver Int. 2021 Feb; 41: 255-260Crossref PubMed Scopus (29) Google Scholar Similarly, irritable bowel syndrome (IBS) considered a diagnosis of exclusion has now moved to a “positive diagnosis”.[16]Manning A. Thompson W.G. Heaton K. Morris A. Towards positive diagnosis of the irritable bowel.Br Med J. 1978; 2: 653-654Crossref PubMed Scopus (1218) Google Scholar Notably, studies have shown that providers who still believe IBS is a diagnosis of exclusion ordered 1.6x more tests and consumed $364 more per patient (p<0.0001), while experts were less likely than nonexperts to endorse IBS as a diagnosis of exclusion (8% vs. 72%; p<0.0001)15. The authors’ particular example of Non-“Hodgkin Lymphoma” is not appropriate. The atypical B-cell blasts in Non-Hodgkin Lymphoma (NHL) simulate the Hodgkin Reed-Sternberg cells, leading to a mistaken diagnosis of classical Hodgkin lymphoma.[17]Wang H.W. Balakrishna J.P. Pittaluga S. Jaffe E.S. Diagnosis of Hodgkin lymphoma in the modern era.Br J Haematol. 2019; 184: 45-59Crossref PubMed Scopus (33) Google Scholar Thus, NHL is an entirely appropriate definition with a definite set of positive clinical, morphological, immunophenotypic, genetic and molecular diagnostic criteria.[17]Wang H.W. Balakrishna J.P. Pittaluga S. Jaffe E.S. Diagnosis of Hodgkin lymphoma in the modern era.Br J Haematol. 2019; 184: 45-59Crossref PubMed Scopus (33) Google Scholar It is not surprising that real-world data reveals a diagnostic gap in NAFLD[18]Alexander M. Loomis A.K. Fairburn-Beech J. van der Lei J. Duarte-Salles T. Prieto-Alhambra D. et al.Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease.BMC Med. 2018; 16: 1-11Crossref Scopus (77) Google Scholar with a recent study that included mainly academic hepatologists suggesting that clinical practice patterns for the management of steatohepatitis frequently deviate considerably from practice guidelines.[19]Rinella M.E. Lominadze Z. Loomba R. Charlton M. Neuschwander-Tetri B.A. Caldwell S.H. et al.Practice patterns in NAFLD and NASH: real life differs from published guidelines.Therap Adv Gastroenterol. 2016; 9: 4-12Crossref PubMed Scopus (45) Google Scholar A path to precision medicine in fatty liver would not be possible under the guise of NAFLD. The shift to MAFLD is likely the first pivotal step towards it. Singh et al. mention that ‘NAFLD’ is diagnosed based on the presence of fatty liver, without significant amounts of alcohol consumption and not having any other causes of liver disease or competing causes of steatosis, as per AASLD guidelines.[20]Chalasani N. Younossi Z. Lavine J.E. 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: 328-357Crossref PubMed Scopus (2317) Google Scholar Then, is it logical to use the term NAFLD despite having other liver diseases or the continuous use of alcohol as is happening currently and is the basis of most population-based studies which only exclude an arbitrary amount of alcohol?21Sanyal A.J. Contos M.J. Sterling R.K. Luketic V.A. Shiffman M.L. Stravitz R.T. et al.Nonalcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome.The Am J Gastroenterol. 2003; 98: 2064-2071Crossref PubMed Scopus (163) Google Scholar, 22Bondini S. Kallman J. Wheeler A. Prakash S. Gramlich T. Jondle D.M. et al.Impact of non-alcoholic fatty liver disease on chronic hepatitis B.Liver Int. 2007; 27: 607-611Crossref PubMed Scopus (89) Google Scholar, 23Paik J.M. Henry L. Golabi P. Alqahtani S.A. Trimble G. Younossi Z.M. Presumed nonalcoholic fatty liver disease among medicare beneficiaries with HIV, 2006–2016.Open Forum Infect Dis. 2020 Jan 7; 7: ofz509Crossref PubMed Scopus (7) Google Scholar Is it not time to correct this ambiguity? The authors question the degree of assertion and the rationale for why the European Liver Patients Association (ELPA) expressed displeasure with the term “NAFLD” and ask whether non-Caucasians were considered in the decision. Indeed, ELPA among 30 other patient associations from around the world have put forth a recent statement explaining in detail the caveats stemming from the misnomer NAFLD from a patient perspective. This consensus group enthusiastically endorsed MAFLD and the diagnostic criteria.[24]Shiha G. Korenjak M. Eskridge W. Casanovas T. Velez-Moller P. Högström S. et al.Redefining fatty liver disease: an international patient perspective.Lancet Gastroenterol Hepatol. 2021 Jan; 6: 73-79Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Various key liver organisations have also endorsed MAFLD as an umbrella term that can be diagnosed by simple, practical, and efficient bedside diagnostic criteria.25Shiha G. Alswat K. Al Khatry M. Sharara A.I. Ormeci N. Waked I. et al.Nomenclature and definition of metabolic-associated fatty liver disease: a consensus from the Middle East and north Africa.Lancet Gastroenterol Hepatol. 2021 Jan; 6: 57-64Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 26Mendez-Sanchez N. Arrese M. Gadano A. Oliveira C.P. Fassio E. Arab J.P. et al.The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease.Lancet Gastroenterol Hepatol. 2021 Jan; 6: 65-72Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 27Eslam M. Sarin S.K. Wong V.W.-S. Fan J.-G. Kawaguchi T. Ahn S.H. 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; : 1-31PubMed Google Scholar Singh et al. refer to their previous work in non-Caucasian populations suggesting that a significant proportion of patients with NAFLD do not have insulin resistance.[28]Singh S.P. Misra B. Kar S.K. Panigrahi M.K. Misra D. Bhuyan P. et al.Nonalcoholic fatty liver disease (NAFLD) without insulin resistance: is it different?.Clin Res Hepatol Gastroenterol. 2015; 39: 482-488Crossref PubMed Scopus (17) Google Scholar Apart from the fact that insulin resistance was not confirmed using the gold standard euglycaemic clamp, 22% of the patients had hypertension, 11% had diabetes, 23% had metabolic syndrome, 84% had dyslipidaemia and significantly more elevations in liver enzymes. This study in fact highlights the unique strengths and importance of the MAFLD definition which integrates metabolic health into the diagnosis, particularly in non-obese patients.[29]Eslam M. Fan J.-G. Mendez-Sanchez N. Non-alcoholic fatty liver disease in non-obese individuals: the impact of metabolic health.Lancet Gastroenterol Hepatol. 2020 Aug; 5: 713-715Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar The authors report that PNPLA3 polymorphism-related steatosis occurs independently of insulin resistance and serum lipid concentrations. However, it should be noted that the association of PNPLA3 with metabolic traits is much more complex than originally considered.[30]Eslam M. George J. Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology.Nat Rev Gastro Hepat. 2019; : 1-13PubMed Google Scholar Although initial studies did not detect a relationship between the p.I148M mutation and serum glucose or lipid concentrations, multiple recent, larger and more robust studies demonstrate that both TM6SF2 rs58542926 and PNPLA3 rs738409 are associated with lower lipid levels and a lower risk of coronary artery disease, but an increased risk of fatty liver and type 2 diabetes mellitus.31Liu D.J. Peloso G.M. Yu H. Butterworth A.S. Wang X. Mahajan A. et al.Exome-wide association study of plasma lipids in >300,000 individuals.Nat Genet. 2017; 49: 1758-1766Crossref PubMed Scopus (255) Google Scholar, 32Meffert P.J. Repp K.D. Völzke H. Weiss F.U. Homuth G. Kühn J.P. et al.The PNPLA3 SNP rs738409: G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort.J Hepatol. 2018; 68: 858-860Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 33Diogo D. Tian C. Franklin C.S. Alanne-Kinnunen M. March M. Spencer C.C. et al.Phenome-wide association studies across large population cohorts support drug target validation.Nat Commun. 2018; 9: 1-13Crossref PubMed Scopus (57) Google Scholar Xia et al. brilliantly extend these concepts, showing an interaction of adiposity and PNPLA3 I148M with metabolic dysfunction. The MAFLD definition overcomes the limitations of heterogeneity implicit in NAFLD that complicates the dissection of such interactions. It is contended that the change to MAFLD can be confusing for the non-hepatologist. In fact, the opposite is very likely the case. As has recently been suggested, MAFLD helps align fatty liver disease in the camp with other metabolic diseases and is likely to be intuitively more meaningful to non hepatologists.24Shiha G. Korenjak M. Eskridge W. Casanovas T. Velez-Moller P. Högström S. et al.Redefining fatty liver disease: an international patient perspective.Lancet Gastroenterol Hepatol. 2021 Jan; 6: 73-79Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 25Shiha G. Alswat K. Al Khatry M. Sharara A.I. Ormeci N. Waked I. et al.Nomenclature and definition of metabolic-associated fatty liver disease: a consensus from the Middle East and north Africa.Lancet Gastroenterol Hepatol. 2021 Jan; 6: 57-64Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 26Mendez-Sanchez N. Arrese M. Gadano A. Oliveira C.P. Fassio E. Arab J.P. et al.The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease.Lancet Gastroenterol Hepatol. 2021 Jan; 6: 65-72Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 27Eslam M. Sarin S.K. Wong V.W.-S. Fan J.-G. Kawaguchi T. Ahn S.H. 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; : 1-31PubMed Google Scholar On another aspect, the authors suggest that the change to MAFLD might paradoxically misdirect therapeutics in the direction of metabolic syndrome alone with a “relatively barren treatment armamentarium”. We strongly disagree with this assertion. MAFLD is a systemic disease, with cardiovascular disease the main cause of death.[34]Vilar-Gomez E. Calzadilla-Bertot L. Wong V.W.S. Castellanos M. Aller-de la Fuente R. Metwally M. et al.Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study.Gastroenterology. 2018; 155: 443Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar,[35]Adams L.A. Lymp J.F. Sauver J.S. Sanderson S.O. Lindor K.D. Feldstein A. et al.The natural history of nonalcoholic fatty liver disease: a population-based cohort study.Gastroenterology. 2005; 129: 113-121Abstract Full Text Full Text PDF PubMed Scopus (2146) Google Scholar Only an integrated multidisciplinary approach to management which takes into consideration the systemic metabolic meta-inflammation and simultaneously considers the impact of investigational drugs on cardiovascular outcomes, is likely to bring new therapeutics to the patient. The shift to MAFLD will also stimulate drug repurposing efforts;[30]Eslam M. George J. Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology.Nat Rev Gastro Hepat. 2019; : 1-13PubMed Google Scholar,[36]Eslam M. George J. Genetic insights for drug development in NAFLD.Trends Pharmacol Sci. 2019; 40: 506-516Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Semaglutide is a case in point.[37]Newsome P.N. Buchholtz K. Cusi K. Linder M. Okanoue T. Ratziu V. et al.A placebo-controlled trial of subcutaneous Semaglutide in nonalcoholic steatohepatitis.New Engl J Med. 2020 Nov 13; https://doi.org/10.1056/NEJMoa2028395Crossref PubMed Scopus (179) Google Scholar We thank the authors for echoing our statement[11]Eslam M. Sanyal A.J. George J. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.Gastroenterology. 2020 May; 158 (1999-2014.e1)Abstract Full Text Full Text PDF PubMed Scopus (634) Google Scholar that the “time is ripe to classify NAFLD”. This is not possible under the old term NAFLD, while MEGA-D does not consider the important distinction between a disease driver and a disease modifier. Chronic hepatitis C is still hepatitis C, whether disease expression is modified by genes or smoking. Adopting MAFLD is the first step in the path to recognising this distinct disease entity. Once recognised, it excludes diseases not meeting the definition and by extension, reduces heterogeneity. In conclusion, MAFLD provides a meaningful working definition and conceptual framework for approaching the disease that is consistent with our evolving understanding of its pathophysiology. The name and definition are readily understood and acceptable to multiple stakeholders and have been validated in multiple studies and endorsed by multiple organisations. This reminds us of the importance in Medicine of distancing “evidence” from “opinion”; only the former can drive the field forward.[7]Fouad Y. Elwakil R. Elsahhar M. Said E. Bazeed S. Gomaa A.A. et al.The NAFLD-MAFLD debate: eminence versus evidence.Liver Int. 2021 Feb; 41: 255-260Crossref PubMed Scopus (29) Google Scholar M.E. and J.G. are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation , University of Sydney , National Health and Medical Research Council of Australia (NHMRC) Program Grants ( APP1053206 , APP1149976 ) and Project grants ( APP1107178 and APP1108422 ). All authors equally contributed to the work. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The following is the supplementary data to this article: Download .pdf (.16 MB) Help with pdf files Multimedia component 1 Non-alcoholic fatty liver disease: Not time for an obituary just yet!Journal of HepatologyVol. 74Issue 4PreviewThere has been a concerted effort to change the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD), and one wonders if it is appropriate and timely to bid adieu to the good old term. Numerous reasons have been put forth to justify this, as outlined in a recently published statement proposing the change.1,2 However, there are considerable flaws in the proposal, and changing NAFLD to MAFLD is unlikely to move the field forward. Full-Text PDF Insights into contribution of genetic variants towards the susceptibility of MAFLD revealed by the NMR-based lipoprotein profilingJournal of HepatologyVol. 74Issue 4PreviewA new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed by a panel of international experts from 22 countries.1 The diagnostic criteria for MAFLD are based on evidence of hepatic steatosis detected using imaging techniques, blood biomarkers/scores and/or liver histology, in addition to one of the following conditions: overweight/obesity, presence of type 2 diabetes, or evidence of metabolic dysregulation.1 Compared with the diagnostic criteria of non-alcoholic fatty liver disease (NAFLD),2 the definition of MAFLD excluded patients with fatty liver unrelated to metabolic dysfunction but included a large number of patients with concomitant metabolic fatty liver and other known liver diseases. Full-Text PDF A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statementJournal of HepatologyVol. 73Issue 1PreviewThe exclusion of other chronic liver diseases including “excess” alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, “positive criteria” to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. Full-Text PDF