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Page 2 of 18 Llamoza-Torres et al. Metab Target Organ Damage 2024;4:40 https://dx.doi.org/10.20517/mtod.2024.64

INTRODUCTION
In the last two decades, there has been a significant global increase in the prevalence of the entities
associated with fatty deposits in the liver, as well as in the incidence of hepatocellular carcinoma (HCC), the
most common primary liver neoplasia . Although the heterogeneity of individuals affected by these
[1-7]
diseases is complex, a deeper understanding of their pathophysiology has led to therapeutic advancements
that have not only changed the treatments of choice but also foreseen a potential revolution in their
[8]
management . The conceptual shift from non-alcoholic fatty liver disease (NAFLD), essentially a diagnosis
of exclusion, to metabolic dysfunction-associated steatotic liver disease (MASLD), which has occurred in
recent years (2020-2023) [9-15] , reflects the confrontation of scientific explanations with clinical reality.

BEYOND THE MASLD TERMINOLOGY CHANGE
In 2000, a nomenclature change from NAFLD to metabolic dysfunction-associated fatty liver disease
[9]
(MAFLD) was proposed . This change aimed to provide greater precision regarding the association with
metabolic dysfunction while retaining the term “fatty”, which many considered stigmatizing. Additionally,
the MAFLD definition required the inclusion of individuals with at least two metabolic risk factors for its
diagnosis.

In 2023, the conclusions of a multidisciplinary consensus (organized by the American Association for the
Study of Liver Disease, AASLD; the European Association for the Study of the Liver, EASL; in collaboration
with the Asociación Latinoamericana para el Estudio del Hígado, ALEH; and with the participation of other
stakeholders, even patient representatives) were published . Based on the Delphi methodology, the
[10]
consensus aimed to evaluate a change in the nomenclature and/or definition of what was previously known
as NAFLD. The consensus focused on five key areas, one of which was to help patients and health
professionals better understand the disease. The term “steatotic liver disease” (SLD) was adopted as an
umbrella term to encompass all conditions leading to hepatic steatosis, including NAFLD, alcoholic-
associated liver disease (ALD), and other related liver conditions [16,17] . This consensus mainly reflects the
intention to associate the presence of cardiovascular risk factors, which are indicators of insulin resistance,
as central drivers of hepatic steatosis in the MASLD concept .
[10]

Since then, relevant communications have concluded that most of the data related to NAFLD or MAFLD
remain valid within the context of the new definition of MASLD, despite the evolved concept indicating
that they are not identical [11-14] . In nearly all studies that have compared the old and new terminologies, the
percentage of agreement for classifying patients as NAFLD and MASLD exceeds 95% [15-17] . This high
concordance suggests that existing data on the epidemiology, natural history, biomarkers, and clinical trials
in the NAFLD population could be extrapolated to MASLD patients . Although the MAFLD terminology
[17]
is still in use and continues to fuel the debate on the change of nomenclature, it omits alcohol intake
assessment in its definition, complicating the identification of high-risk populations. Emerging data suggest
that there are notable differences, mainly in mortality rates and the risk of complications such as hepatic
fibrosis, cardiovascular disease, and chronic kidney disease [18-21] . Pennisi et al. evaluated the prognostic
impact of NAFLD and MAFLD on overall mortality, cardiovascular mortality, non-fatal cardiovascular
events, risk of developing chronic kidney disease, and extrahepatic neoplasms. They reported higher overall
mortality in the MAFLD population; however, it should be noted that the studies included in their analysis
showed significant heterogeneity (I = 73%; P < 0.01) for overall mortality, with a 12%-15% higher mortality
2
rate in MAFLD compared to NAFLD .
[22]
Additionally, metabolic dysfunction-associated steatohepatitis (MASH) has been proposed to replace non-
alcoholic steatohepatitis (NASH) to describe patients with MASLD and active necroinflammation