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Targher et al. Hepatoma Res 2020;6:64 I http://dx.doi.org/10.20517/2394-5079.2020.71 Page 3 of 9

[6]
1980, Ludwig et al. coined the term «nonalcoholic
steatohepatitis»
[7]
1986, Schaffner and Thaler coined the term «nonalcoholic fatty
liver disease»
2002, A report of the AASLD single topic conference suggested
«metabolic steatohepatitis» as alternative term to NAFLD/NASH
but no consensus was reached
2005, Loria et al. proposed a change of name that should
[9]
incorporate either «metabolic» or «insulin resistance»

2009, An EASL special conference proposed to change the name 2009, Brunt [11] proposed to change to «metabolic syndrome
to «metabolic fatty liver disease» steatohepatitis (MESH)» or «obesity-related fatty liver disease»

2011, Balmer and Dofour [12] proposed the term «metabolic
syndrome-associated fatty liver disease (MAFLD)»

2017, Bellentani and Tiribelli [13] proposed the term «metabolic-
associated fatty liver (MAFL)»

2020, An international consensus panel proposed the term
«metabolic-(dysfunction) associated fatty liver disease 2020, An international expert panel proposed a new definition for
(MAFLD)» the diagnosis of «metabolic-(dysfunction) associated fatty liver
disease (MAFLD)»

Figure 1. Schematic timeline of key suggestions for the revising the nomenclature of fatty liver disease from NAFLD to MAFLD [4-13] .
NAFLD: nonalcoholic fatty liver disease; MAFLD: metabolic dysfunction-associated fatty liver disease

It is important to highlight that these “positive” diagnostic criteria recognize that MAFLD can also
frequently co-exist with other conditions (e.g., significant alcohol consumption, viral hepatitis or other
known chronic liver diseases), but the exclusion of these conditions is not a prerequisite for the diagnosis
of MAFLD. Indeed, one of the advantages of the proposed diagnostic criteria for MAFLD is that they do
not rely on exclusion of significant alcohol intake to establish the diagnosis. Individuals with MAFLD who
also have one (or more) of these conditions should be defined as having dual (or more) aetiology of fatty
[5]
liver disease , and it is likely that these individuals will have a different natural history and response to
different treatments. For instance, previous studies have shown that a significant proportion of the general
adult population (e.g., up to nearly 1% of United States individuals from the National Health and Nutrition
[20]
Examination Survey database 2003-2014) may be affected by both alcoholic disease and NAFLD (referred
as BAFLD) and these patients tend to have more severe liver-related outcomes, given the synergistic
interactions between alcohol consumption and features of the metabolic syndrome, such as obesity and
type 2 diabetes mellitus [20,21] .

The rationale for the use of these “positive” diagnostic criteria for MAFLD largely stem from the fact
that there is a strong pathophysiological link between this liver disease and the presence of underlying
abnormalities in metabolic health (namely overweight/obesity, type 2 diabetes, insulin resistance or other
metabolic risk abnormalities) [17-19,21-29] . In addition, there is also convincing evidence that the coexistence of
these metabolic risk abnormalities is not only one of the strongest risk factors of liver disease progression
but also extra-hepatic clinical outcomes (mainly cardiovascular disease, chronic kidney disease and
certain types of extra-hepatic cancers) in this patient population [17-19,23-31] . As depicted in Figure 2, the new
diagnostic criteria for MAFLD would also be able to capture the whole phenotypical spectrum of fatty
liver disease from that associated with metabolically unhealthy normal weight to metabolically unhealthy
obesity.