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New terms for fatty liver disease other than MAFLD: Time for a reality check

  • Nahum Méndez-Sánchez
    Correspondence
    Corresponding author. Address: Liver Research Unit, Medica Sur Clinic & Foundation and Faculty of Medicine. National Autonomous University of Mexico, Mexico City, Mexico. Tel.: (+525) 55424-4629, fax: (+525)55 666-4031.
    Affiliations
    Liver Research Unit, Medica Sur Clinic & Foundation, Mexico

    Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
    Search for articles by this author
  • Shreya C. Pal
    Affiliations
    Liver Research Unit, Medica Sur Clinic & Foundation, Mexico

    Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
    Search for articles by this author
Published:August 18, 2022DOI:https://doi.org/10.1016/j.jhep.2022.08.009
      To the Editor:
      In 2020 a landmark consensus by international experts put forth a comprehensive proposal for renaming and defining what was previously termed non-alcoholic fatty liver disease (NAFLD). The conceptualised framework changed the disease from one that was diagnosed when all other causes for hepatic steatosis were excluded (hence removing the “non” word) and its overemphasis on alcohol. The new term metabolic (dysfunction) associated fatty liver (MAFLD) and its diagnostic criteria acknowledged the dominant role of metabolic dysregulation in disease pathogenesis. Despite the multiple positive attributes that have been supported by mounting evidence of its superior clinical utility, controversy still exists.
      • Alharthi J.
      • Gastaldelli A.
      • Cua I.H.
      • Ghazinian H.
      • Eslam M.
      Metabolic dysfunction-associated fatty liver disease: a year in review.
      • Eslam M.
      • Ahmed A.
      • Després J.-P.
      • Jha V.
      • Halford J.C.
      • Chieh J.T.W.
      • et al.
      Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases.
      • Eslam M.
      • Alkhouri N.
      • Vajro P.
      • Baumann U.
      • Weiss R.
      • Socha P.
      • et al.
      Defining paediatric metabolic (dysfunction)-associated fatty liver disease: an international expert consensus statement.
      • 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.
      • Eslam M.
      • Sanyal A.J.
      • George J.
      • Sanyal A.
      • Neuschwander-Tetri B.
      • Tiribelli C.
      • et al.
      MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.
      Importantly, during the course of this debate NAFLD and MAFLD remain the only two alternatives for the disease nomenclature.
      Recently, multiple potential alternative terms have been proposed. From our perspective, it is time for a reality check to distinguish the genuine from the hype. First of all, how did MAFLD come about? A group of 31 experts engaged in a 2 round Delphi process to consider alternative names, recognising that NAFLD for various reasons did not serve the field. In the first round, experts were asked to come up with any and all alternative terms (i.e. an open question). In the second round, the panel voted on their top 6 choices from the names suggested in round one. In round two, MAFLD was supported by ∼70% of participants.
      • Eslam M.
      • Sanyal A.J.
      • George J.
      • Sanyal A.
      • Neuschwander-Tetri B.
      • Tiribelli C.
      • et al.
      MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.
      This data was published as a “proposed” nomenclature after which extensive clinical research ensued across the world, validating the name and its diagnostic criteria.
      • 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.
      Hence, one could legitimately ask what can we expect from repeating the same process again apart from feeding a sense of confusion and division. Notably, none of the other terms proposed have been accompanied by a set of diagnostic criteria for adults and children that tells us what the disease is. Rather, what all the other terms have in common is the “non”-definition of NAFLD clothed in a term that does not have the word “non” and perhaps “alcohol”.
      Second, it should be noted that disagreement around MAFLD may be less than initially assumed and has focused on a small but vocal group interested in maintaining the status quo. MAFLD has received substantial endorsement from multiple pan-national and national societies, and stakeholders.
      • Shiha G.
      • Korenjak M.
      • Eskridge W.
      • Casanovas T.
      • Velez-Moller P.
      • Högström S.
      • et al.
      Redefining fatty liver disease: an international patient perspective.
      At the apex, >1,000 stakeholders including hepatologists, endocrinologists, paediatricians, primary-care providers, pathologists, patient advocates, nurses, nutritionists, and pharmaceutical experts from >134 countries endorsed the term.
      • Méndez-Sánchez N.
      • Bugianesi E.
      • Gish R.G.
      • Lammert F.
      • Tilg H.
      • Nguyen M.H.
      • et al.
      Global multi-stakeholder endorsement of the MAFLD definition.
      Does this not say something?
      Third, querying PubMed has shown that >10% of publications since coinage of MAFLD have opted to use that term (this does not include articles that have mentioned both terms), which is double that from the year before. If the same trends hold, within 2 years approximately 40-50% of publications will be using MAFLD not NAFLD. By analogy, the terms NAFLD/NASH took over 15 years from when first coined to reach to the same number of publications that MAFLD has reached in 2 years. This has been in the context of substantial barriers at the publication interface.
      The number of citations gives another proxy of academic acceptance. The two original publications on MAFLD
      • 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.
      ,
      • Eslam M.
      • Sanyal A.J.
      • George J.
      • Sanyal A.
      • Neuschwander-Tetri B.
      • Tiribelli C.
      • et al.
      MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.
      are cited over 12.4 fold more than the two opposing editorials
      • Younossi Z.M.
      • Rinella M.E.
      • Sanyal A.J.
      • Harrison S.A.
      • Brunt E.M.
      • Goodman Z.
      • et al.
      From NAFLD to MAFLD: implications of a premature change in terminology.
      ,
      • Ratziu V.
      • Rinella M.
      • Beuers U.
      • Loomba R.
      • Anstee Q.M.
      • Harrison S.
      • et al.
      The times they are a-changin'(for NAFLD as well).
      (2,373 vs. 191 cites, respectively as per 18 July 2022). In addition, we analysed internet search patterns over time using Google Trends for MAFLD compared to NAFLD, which showed that there was a continuous increase in public interest in MAFLD that in some regions (e.g., Chile, Mexico and Spain) reached comparable levels to the term NAFLD, despite differences in the time scale of availability of both terms.
      MAFLD has been translated into the clinic in multiple regions around the world and numerous clinical recommendations have been published.
      • Eslam 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.
      Studies have shown the positive implications of the transition to MAFLD in increasing disease awareness among patients, healthcare providers and for increasing attention to MAFLD at conferences across countries and health systems.
      • Alharthi J.
      • Gastaldelli A.
      • Cua I.H.
      • Ghazinian H.
      • Eslam M.
      Metabolic dysfunction-associated fatty liver disease: a year in review.
      A completely new name other than MAFLD merely undermines the momentum and stalls progress.
      In conclusion, there is no question on the necessity to redefine fatty liver disease. All the other terms that have been proposed fall far short as descriptors and fail to define the disease. Therefore, scrutiny of these other suggestions requires a reality check. Overlooking the growing evidence and support for MAFLD is like an ostrich with its head in the sand. Not acknowledging the data does not change the fact that the data exists. Whether we like it or not, MAFLD is heavily embedded in the literature and there is no turning back. In our view, moving the discussion away from the debate on MAFLD-NAFLD is unrealistic and has no potential to move the field forward. Instead, we believe that building on the momentum generated by the transition to MAFLD is the way forward.

      Financial support

      The authors received no financial support to produce this manuscript.

      Authors' contributions

      Authors contributed equally to all aspects of the manuscript.

      Conflict of interest

      The authors declare that they have no conflicts of interest.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following are the supplementary data to this article:

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