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The first change was announced in 2020, following a survey and Delphi process, where experts proposed the
[10]
term MAFLD . The primary aim of this change was to shift from a negative nomenclature of “non-
[10]
alcoholic” to a more positive diagnosis . The term MAFLD encompasses all patients with fatty liver who
have at least two of the metabolic risk factors: waist circumference ≥ 102/88 in Caucasian men/women and
≥ 90/80 in Asian men/women; blood pressure ≥ 130/85 mm of Hg; plasma high-density lipoprotein levels
< 40 mg/dL in men and 50 mg/dL in women; the presence of prediabetes, defined as fasting glucose levels
between 5.6-6.9 nmol/L, or a 2-h postprandial glucose levels between 7.8-11.0 mmol/L, or HbA1c levels
between 5.7%-6.4%; Homeostatic model assessment for insulin resistance (HOMA-IR) score ≥ 2.5; and
plasma high-sensitivity C-reactive protein levels >2mg/L [10,11] . Initially, MAFLD was proposed as an umbrella
term; however, concerns were later raised regarding the presence of other co-existing etiologies that may
ultimately influence the natural course of the disease and must be addressed when treating these patients .
[12]
The need for this change in nomenclature is supported by the following reasons. The term “metabolic”
reflects the pathophysiolsogic basis of the disease, focusing on a positive attribute rather than the exclusion
of ethanol abuse. Therefore, the diagnosis can be made more quickly and simply, without the need to rule
out other liver diseases. It is hoped that this change in nomenclature may generate renewed enthusiasm
among healthcare personnel to identify these patients and promote a more holistic approach to managing
the condition. Additionally, it helps identify patients with advanced fibrosis, enabling the stratification of
those at high risk of mortality. Patients with dual etiologies of fatty liver (e.g., Hepatitis C and NAFLD), who
were previously managed based on only one dominant cause, may receive a more comprehensive treatment
approach. Finally, the potentially stigmatizing term “Alcohol” is avoided in MAFLD.

This nomenclature received wide acceptance [11,13,14,15] but was also criticized for several reasons. While it was
widely believed that the pathogenesis of MAFLD was similar to that of metabolic syndrome, most of the
drugs used to treat hypertension, diabetes, hyperlipidemia, and other related conditions proved ineffective
in treating MAFLD. For example, statins, antihypertensive drugs, and many antidiabetic or lipid-lowing
medications have not shown benefit for MAFLD patients. Additionally, the role of genetic factors, intestinal
dysbiosis, and sarcopenia, which play a major role in the pathophysiology of MAFLD, was ignored due to
the excess focus on metabolic components. MAFLD also failed to account for the additive/synergistic effects
of viral hepatitis or ethanol abuse on the natural progression and prognosis of fatty liver disease.
Furthermore, reports have highlighted a significant subset of patients with “lean NAFLD”, where metabolic
syndrome may not be prominent . Some authors spoke frankly against the name change, stating that it is
[16]
not supported in their regions [17,18,19] .

Amid ongoing debates, the second change in nomenclature was introduced by another Delphi consensus
meeting . Surprisingly, many of the experts who participated in the first Delphi consensus were also
[11]
involved in the second. The rationale for this second name change was threefold. First, the term “Fatty” was
now considered stigmatizing for patients. Second, experts wanted to expand the spectrum to include alcohol
and other causes of fatty liver, recognizing that many patients may have multiple contributing factors.
Finally, the change aimed to address the “Potential negative impact of changes in diagnostic criteria for the
[20]
disease in terms of biomarker and therapeutic development” . To reflect these considerations, a new term,
Met-alcoholic liver disease (ALD), was introduced, which represents a middle point in the spectrum of
illness, positioned between MASLD (Ethanol abuse of less than 30 g per day in males and less than 20 g per
day in females) at on one end and ALD at the other end (Ethanol abuse of more than 60 g per day in males
and 50 g per day in females) . Additionally, patients with uncommon etiologies of fatty liver, such as drug-
[11]
induced steatosis, HCV infection, and monogenic causes of steatosis (Secondary SLD), were included under
the classification of specific etiology MASLD. Monogenic causes, in particular, must be actively considered