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NAFLD is a heterogeneous disease with a global distribution that varies significantly due to variations in
genetics, lifestyles, and socioeconomic factors [10,14] . The highest prevalence rates have been previously
[3]
reported in the Middle East and South America, while the lowest rates were seen in Africa . In Asia, a
[15]
gradient from higher rates in urban areas to lower prevalence in rural areas is reported .

In Latin America, the epidemic of obesity, type 2 diabetes mellitus (T2DM], and metabolic syndrome has
led to a growing burden of NAFLD . Reported prevalence rates in these regions range from 24% to 68%,
[16]
which is likely influenced by a higher prevalence of T2DM, obesity, and genetic predisposition related to the
presence of the PNPLA3 polymorphism [17-19] .

The prevalence of metabolic syndrome, a key risk factor for the development of NAFLD, has been reported
[16]
to be among the highest globally, according to a study examining several Latin American countries .
Moreover, the consumption of highly processed foods, refined sugars, and saturated fatty acids has
contributed to the increasing prevalence of NAFLD in this region .
[14]

This growing epidemic of fatty liver disease continues to worsen and is expected to persist in the coming
years, driven by continuing trends in obesity and metabolic risk factors . As a result, the increasing
[16]
prevalence is expected to lead to a higher burden of advanced liver disease, complications, and increased
cardiovascular morbidity/mortality .
[20]

The epidemiology of NAFLD also diverges between adult and pediatric populations. The prevalence of
NAFLD rises with age in adults and reaches its highest level in middle age . Similarly, in children, NAFLD
[3]
prevalence increases with age, peaking at 15 years . There are also significant sex and ethnic variations in
[12]
the prevalence of NAFLD. Boys, in general, have higher rates of NAFLD than girls, and Hispanic and Asian
children have higher rates than White and African American children .
[12]

Sex-related differences are observed in both adult and pediatric NAFLD. Among adults, men are more
frequently and severely affected by NAFLD during reproductive age, whereas women start to develop an
increased risk post-menopause, indicating a protective role of estrogen . In children, boys have higher
[21]
rates of NAFLD compared to girls . These sex differences might be associated with differences in body
[12]
composition, as well as etiological factors such as hormonal and genetic factors . Computer modeling has
[22]
further predicted that male and female livers are metabolically distinct, with different regulatory
[21]
mechanisms contributing to sex-specific metabolic outcomes .
The responses to NAFLD treatments may also vary between adults and children. Lifestyle changes, such as
diet and exercise, remain the foundation of treatment for both groups [3,23] . Nonetheless, adherence to these
lifestyle changes can be difficult, especially in adolescents . Although many pharmacological agents have
[24]
shown promise in improving adult NAFLD, their safety and effectiveness in children remain unproven [3,23]
[Figure 1].

PATHOPHYSIOLOGY
Although the underlying pathophysiology of fatty liver disease is similar between the child and adult
populations, there are significant differences in clinical presentation and disease progression . In pediatric
[25]
cases, the presentation of NAFLD is more prominent during the peripubertal phase, with the mean age of
[12]
diagnosis around 12-13 years . Pediatric NAFLD is closely linked to obesity and associated insulin
resistance, although it has also been reported in non-obese children .
[26]