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Page 2 of 16 Iruzubieta et al. Metab Target Organ Damage. 2025;5:10 https://dx.doi.org/10.20517/mtod.2024.143

INTRODUCTION
The recognition of hepatic steatosis in patients with high alcohol consumption dates back to 1836, when
[1]
Addison first described the condition . Later, in 1980, Ludwig et al. identified a similar histological pattern
in patients without alcohol consumption, leading to the introduction of the term non-alcoholic
[2]
steatohepatitis (NASH) . This discovery laid the foundation for the broader concept of non-alcoholic fatty
liver disease (NAFLD), a term that encompasses a spectrum of conditions ranging from simple steatosis to
NASH, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Over the past four decades, the prevalence
of NAFLD has increased exponentially, paralleling the rise in obesity, type 2 diabetes mellitus (T2DM), and
metabolic syndrome (MetS). Today, it is the most common chronic liver disease worldwide, affecting
[3]
approximately 38% of the global population . In fact, NAFLD has become the second leading cause of end-
stage liver disease and primary liver cancer in adults. However, the impact of NAFLD extends far beyond
liver-related complications. Cardiovascular disease (CVD) remains the leading cause of mortality in
NAFLD patients, underscoring the strong association between liver disease and systemic metabolic
dysfunction . The natural history of NAFLD involves a bidirectional relationship with components of
[4]
MetS, particularly T2DM, which not only increases the risk of hepatic fibrosis and cirrhosis but is also
exacerbated by NAFLD itself. NAFLD has been shown to impair glycemic control and increase the risk of
[5]
both microvascular and macrovascular complications . This intricate interplay between hepatic and
systemic metabolic dysfunction highlights the need for a classification that more accurately reflects the
metabolic drivers of disease progression.

In response to these challenges, the terminology for steatosis-related liver diseases has evolved significantly.
In 2020, Eslam et al. proposed the term “metabolic-associated fatty liver disease” (MAFLD) to emphasize
the link between hepatic steatosis and metabolic dysfunction . However, the adoption of MAFLD met with
[6]
resistance due to the absence of a global consensus. In 2023, following a four-round Delphi process, an
international panel of 225 experts, including hepatologists, gastroenterologists, endocrinologists, primary
care physicians, and patient advocates, endorsed the term “metabolic dysfunction-associated steatotic liver
[7]
disease” (MASLD) . Supported by leading organizations such as the American Association for the Study of
Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the Latin
American Association for the Study of the Liver (ALEH), MASLD aimed to remove the stigma associated
with the term “fatty” and to highlight the primary role of metabolic dysfunction in the disease’s
pathogenesis.

The broad international consensus achieved promotes uniformity in the application of this terminology.
However, this consensus not only led to the adoption of the term MASLD but also introduced “steatotic
liver disease” as an umbrella term encompassing all clinical entities characterized by hepatic steatosis. This
shift breaks down the artificial division between the underlying causes of hepatic steatosis, acknowledging
that these causes are often multifactorial and may co-occur, especially in cases where alcohol consumption
and metabolic factors align, a condition now termed “metabolic and alcohol-related liver disease”
(MetALD). This standardized terminology has raised awareness of this liver disease, creating opportunities
to enhance the training of physicians across multiple specialties in this pathology. It also opens new avenues
for research, treatment development, and the study of dual conditions such as MetALD.

Despite the broad international consensus supporting MASLD, several challenges remain. Some researchers
and clinicians remain hesitant to abandon NAFLD, given its extensive use in scientific literature and clinical
guidelines. Furthermore, the implementation of MASLD may pose educational and logistical challenges,
especially in regions where clinical practice has yet to fully transition to the updated classifications. In this
review, we emphasize the benefits of the new nomenclature as well as some of its controversial aspects. To