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particle before it) to a positive definition related to metabolic dysfunction in both the metabolic
dysfunction-associated fatty liver disease (MAFLD) and MASLD definitions. While stigma on alcohol
consumption is frequently perceived, fewer data are available on whether the word “non-alcoholic”
contained in NAFLD/NASH may also carry this unpleasant burden.

The potential stigma related to the term NAFLD has been recently investigated in a global survey completed
[62]
by both patients and healthcare providers . The survey showed that the degree of perceived stigma was
highly heterogeneous across countries (it was generally higher in the United States) and differed
significantly between patients and physicians. Overall, patients reported more commonly stigmatization
related to overweight-obesity (26%) than related to NAFLD (8%). They generally felt similarly comfortable
with the terms NAFLD and MAFLD. Among practitioners, the word “nonalcoholic” was considered
stigmatizing by 34% of respondents, while the word “fatty” by 38%. These discrepancies and geographical
differences led some Authors to propose continuing the use of both the NAFLD and MAFLD/MASLD
[63]
terminology within the scientific community .

COMPARING THE DEFINITIONS OF NAFLD, MAFLD AND MASLD
Diagnostic criteria for the three considered definitions are shown in Figure 3. As described before,
international guidelines recommended diagnosing NAFLD by demonstrating excessive fat content in the
liver (steatosis in ≥ 5% of hepatocytes as evaluated through liver biopsy or histology). Moreover, they
recommended excluding other causes of steatosis (such as specific medications and genetic disorders), co-
existence of other forms of chronic liver disease (such as chronic viral hepatitis, autoimmune disease,
hemochromatosis, and Wilson’s disease, among others) and the concomitant use of significant amounts of
alcohol [64-68] . Agreement on the exact threshold for defining excessive alcohol consumption is not universal;
it has been defined as ≥ 30 g/day in men and ≥ 20 g/day in women, or 2 standard drinks per day for men and
1 standard drink per day for women.

In contrast, to diagnose MAFLD, evidence of liver steatosis may come from histology, imaging techniques,
or even serum-based biomarkers [such as the fatty liver index (FLI)]. Furthermore, metabolic dysfunction
[69]
needs to be present . It is defined as the presence of overweight or obesity (with BMI thresholds differing
according to ethnicity), type 2 diabetes (T2D) or, in normal-weight individuals, as the presence of at least
two of the following features: increased waist circumference, elevated blood pressure, elevated plasma
triglycerides, low plasma High-density lipoprotein (HDL-cholesterol), pre-diabetes, an elevated homeostatic
model assessment of insulin resistance (HOMA-IR), an elevated high-sensitivity C-reactive protein.
Importantly, exclusion of other forms of chronic liver disease and significant alcohol consumption is not
needed to perform the diagnosis, leading to the possibility of diagnosing patients with more than one
chronic liver condition.

The recent Delphi consensus, in an effort to provide a more transparent, universal, and systematic process,
redefined the whole landscape of liver steatosis. When steatosis is present (mainly detected through imaging
or histology), a diagnosis of steatotic liver disease (SLD) can be made . Within SLD, MASLD is
[70]
characterized by the absence of significant alcohol consumption (using 30/20 g/day in men and women,
respectively, as a threshold), other specific etiologies (e.g., drug-induced liver injury or monogenic forms),
and evidence of at least one of the following cardio-metabolic criteria: elevated BMI or waist circumference,
pre-diabetes or T2D, elevated blood pressure, elevated triglycerides, and low HDL-cholesterol. In the case of
steatosis, metabolic dysfunction, and a higher alcohol intake (20-50 and 30-60 g/day in women and men,
respectively), a diagnosis of “MASLD and increased alcohol intake (MetALD)” can be made. For even
higher alcohol consumption, a diagnosis of ALD is recommended. Finally, in the case of SLD without