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Page 2 of 9 Targher et al. Hepatoma Res 2020;6:64 I http://dx.doi.org/10.20517/2394-5079.2020.71

MAIN TEXT
Nonalcoholic fatty liver disease (NAFLD) is a growing global health problem that affects about a quarter
[1-3]
of the world’s adult population and poses a major health and economic burden to all societies . Recently,
two new position articles, published by a panel of international experts from 22 countries, have proposed
a change of terminology and definition for NAFLD, called “metabolic dysfunction-associated fatty liver
[4,5]
disease” (MAFLD) .
As summarized in the schematic Figure 1, over the last two decades there have been concerns expressed
by both individual experts and some special conferences of scientific societies (an AASLD 2003 single
topic conference and an EASL 2009 special conference, respectively) regarding the inaccuracy and possible
“negative” consequences of using the term “NAFLD” to describe a fatty liver disease associated with
[6]
metabolic dysfunction [6-13] . Since the initial descriptions in the early 1980s by Ludwig et al. , Schaffner
and Thaler , who coined the terms of nonalcoholic steatohepatitis (NASH) and NAFLD, respectively, to
[7]
describe a fatty liver disease arising in the absence of significant alcohol consumption, there have been
major conceptual advances in our understanding of the complex pathophysiological mechanisms of this
common liver disease.

Although the change of nomenclature from NAFLD to MAFLD that has been recently proposed by
the panel of international experts is still under discussion, it is important to underline that this change
in terminology is not merely a semantic revision, but can also represent the first step toward a better
identification of this common and burdensome metabolic liver disease for improved health promotion,
case identification, patient awareness, ongoing clinical trials and health services delivery [5,6,14-16] .

Criteria for MAFLD diagnosis
The current definition of NAFLD is based on the presence of hepatic steatosis (detected by liver biopsy,
imaging methods or blood biomarkers/scores) in the absence of significant alcohol consumption (though
the currently recommended cut-offs to define “significant” alcohol consumption are arbitrary) and the
exclusion of other secondary causes of hepatic steatosis [17-19] . Interestingly, the newly proposed definition of
MAFLD shifts from a liver disease of “exclusion” (i.e., non-alcoholic fatty liver without coexisting known
causes of fatty liver) to one of “inclusion”, as the newly proposed diagnostic criteria are based on the
presence of hepatic steatosis, in addition to one of the following three criteria (namely overweight/obesity,
presence of established type 2 diabetes mellitus, or evidence of metabolic dysregulation), regardless of daily
[5]
alcohol consumption and other concomitant liver diseases . A flowchart for the proposed simple criteria
for the diagnosis of MAFLD in adult individuals is depicted in Figure 2. It is important to underline that
these diagnostic criteria do not apply to paediatric population (< 18 years), because different cut-off points
for defining the presence of overweight/obesity and other metabolic risk abnormalities should be used in
children and adolescents. As also shown in this figure, the criteria proposed for diagnosing the presence of
metabolic dysregulation among lean/normal weight individuals with hepatic steatosis who do not have type
2 diabetes, are the presence of at least two metabolic risk factors from: (1) those risk factors that are widely
used to identify the metabolic syndrome (using ethnic- and country-specific cutoff points of increased
[20]
waist circumference) ; (2) a homeostasis model assessment-estimated insulin resistance score ≥ 2.5; or (3)
a plasma high sensitivity-C-reactive protein (hs-CRP) level > 2 mg/L. It is well known that the metabolic
syndrome is a complex of inter-related risk factors for both type 2 diabetes and cardiovascular disease.
These risk factors include dysglycaemia, hypertension (or raised blood pressure), atherogenic dyslipidemia
(typically defined by increased plasma triglycerides and low high-density lipoprotein cholesterol) and
[20]
obesity (particularly increased abdominal adiposity) . Interestingly, the new definition of MAFLD also
includes elevated plasma hs-CRP levels as one of the metabolic risk factors, because it is well established
that this plasma inflammatory biomarker (mostly secreted by the liver) is also often increased with
cardiometabolic disorders.