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Page 2 of 8 Gómez-Mendoza et al. Metab Target Organ Damage. 2025;5:24 https://dx.doi.org/10.20517/mtod.2024.108

INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) has emerged as a growing and leading health problem, not only
in adults but increasingly in children. It is defined as the accumulation of fat in the liver without significant
alcohol consumption . NAFLD is characterized by hepatic steatosis, identified through imaging or
[1,2]
[3]
histology, in the absence of secondary causes of fat accumulation . Meanwhile, nomenclature and
diagnostic definitions for fatty liver disease have changed markedly, with the initial change from NAFLD to
metabolic dysfunction-associated fatty liver disease (MAFLD), and more recently from MAFLD to
[4,5]
metabolic dysfunction-associated steatotic liver disease (MASLD) . The gradual shifts in this definition
demonstrate a growing knowledge of the complex relationship between the disease and metabolic
dysfunction, underscoring the need for routine and accurate guidelines for diagnosis.

NAFLD, abbreviated as NAFLD, was initially described as hepatic steatosis occurring in the absence of
[3]
excessive alcohol consumption . This definition, while widely accepted, had drawbacks, not least its
exclusionary nature. The term “non-alcoholic” characterizes the disease by what it is not, rather than by its
[4]
underlying pathophysiology . This resulted in the introduction of the term “Metabolic Dysfunction-
Associated Fatty Liver Disease”, abbreviated as MAFLD , which is a more comprehensive and
[6]
pathophysiologically relevant terminology. MAFLD is a major conceptual shift from the previous diagnosis;
it takes into account fatty liver known to be related to metabolic dysfunctions with obesity, type 2 diabetes,
dyslipidemia, and insulin resistance . MAFLD differed from NAFLD in that the diagnostic criteria for
[6,7]
MAFLD absolved liver steatosis from having to occur in the absence of significant alcohol consumption yet
required its co-occurrence with at least one of a number of cardiometabolic risk factors . It also includes
[5]
individuals with moderate alcohol consumption who exhibit metabolic risk factors, thereby addressing a
clear shortcoming of the original NAFLD definition.

The current evolution in terminology resulted in the erm “Metabolic Dysfunction-Associated Steatotic Liver
[4,8]
Disease”, abbreviated as MASLD . This change is intended to more accurately reflect the central role of
metabolic dysfunction in the disease pathogenesis, hile also helping to reduce the stigma associated with
earlier terms. MASLD is defined as steatotic liver disease (SLD) in individuals with at least one cardio-
metabolic risk factor and without harmful alcohol consumption . In addition, a novel category, metabolic
[8]
dysfunction and alcohol-related liver disease (MetALD), has also been proposed, which is defined as
MASLD plus moderate alcohol intake .
[4]

These conceptual shifts have greatly altered the way we think about fatty liver disease. The transition from
NAFLD to MAFLD and, more recently, MASLD has expanded the disease concept and scope, emphasizing
the strong association of the disease with metabolic disorders and encompassing metabolic dysfunction as
pivotal in its pathogenesis . The updated definitions have also helped researchers and practitioners in their
[9]
efforts to include more diverse patient populations in research, allowing for a better characterization of the
[5]
disease’s epidemiology, natural history, and response to treatment .

EPIDEMIOLOGY
NAFLD has become a global epidemic, with prevalence estimates ranging from 23% to 42% in adults [10,11] .
The prevalence is also growing in the pediatric population, with a reported prevalence between 5% and 10%
in the general pediatric population, with even higher rates observed in obese children . In contrast, the
[12]
global prevalence of NAFLD in adolescents has risen from 3.73% in 1990 to 4.71% in 2019. Notably, this
disease exhibits a male predominance in this specific group, with a higher prevalence in males compared to
females .
[13]