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Page 6 of 9 Targher et al. Hepatoma Res 2020;6:64 I http://dx.doi.org/10.20517/2394-5079.2020.71

Figure 3. Concordance between MAFLD and NAFLD diagnostic criteria in the Third National Health and Nutrition Examination Survey
(NHANES) 1988-1994 database. Data are extrapolated from the study by Lin et al. [32] . This figure is quoted with permission from
Targher G. [33] . *Metabolic dysfunction was defined according to MAFLD diagnostic criteria. MAFLD: metabolic dysfunction-associated
fatty liver disease; NAFLD: nonalcoholic fatty liver disease; ALD: alcoholic liver disease

That said, further large cohort studies are needed to validate and corroborate the aforementioned findings
in European, American and Asian populations (where the overall prevalence of “lean” NAFLD is greater
[34]
than in United States) and, most importantly, to examine the risk of developing adverse liver-related and
extra-hepatic outcomes (e.g., cardiovascular disease, chronic kidney disease and extra-hepatic cancers) in
patients with MAFLD compared with those with NAFLD. In addition, further research is also needed to
better understand the risk of disease progression amongst “lean” NAFLD individuals without any metabolic
dysregulation.

CHALLENGES AND THE WAY FORWARD
In addition to the challenges for the MAFLD field that have been outlined in the two new position
[4,5]
papers (e.g., definition of “metabolic health”, different disease subtypes) , words of caution have also
been expressed by a distinguished group of United States experts regarding the possible implications of a
[35]
premature change in NAFLD terminology . In particular, although these colleagues are in agreement that
the new term MAFLD reflects more accurately the relevant metabolic risk factors than the age-old term
NAFLD, they also suggest that a change in terminology for a disease entity is only justified when there is
[35]
a better understanding of its pathogenesis, risk stratification and molecular phenotyping . That said, one