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Page 10 of 17 Gulati et al. Metab Target Organ Damage 2024;4:9 https://dx.doi.org/10.20517/mtod.2023.45

[56]
children with biopsy-proven MASLD . Multivariate analyses controlling for age, sex, and severity of
obesity found a significant association between elevated TSH and MASLD. This association has been found
in both pediatric and adult Hispanic and non-Hispanic populations; thus, this association does not
currently appear to be race-specific. A study was published in 2022 that analyzed antinuclear antibody
(ANA) status in 38 Hispanic children with a histologic diagnosis of MASLD . The analysis found that in
[57]
this population, a positive ANA result is associated with insulin resistance and lower HDL levels and thus
concluded that ANA may be more indicative of pro-inflammatory activity of adipose tissue rather than an
autoimmune hepatitis process. Although this association between ANA and insulin resistance was found, it
cannot currently be assumed that the association is driven by race or ethnicity. Each of these studies
contributes to understanding the pathogenesis of MASLD in Hispanic populations, a process that is likely to
begin at an early age. Further research is needed to elucidate the nuances of how these hormones and
antibodies influence the pathogenesis of MASLD within various populations.

Contribution of environmental exposures to increased predominance of MASLD
Although the exact mechanism is unknown, environmental exposures are believed to play a role in the
pathogenesis of MASLD. More research has been conducted recently, including experiments among
animals, identifying an association of exposures to mercury and arsenic with MASLD. Frediani et al.
investigated 8518 multiethnic individuals from the National Health and Nutrition Survey (2005-2014) and
found that there was a positive association between urinary arsenic exposure level and risk of MASLD
among United States adolescents and adults, and interestingly, the association was the highest among
Mexican Americans . Similar effects have been found with other exposures. A study published in 2018 of
[58]
944 adolescents found that individuals with higher quartiles of exposure to bisphenol-A (BPA), a chemical
used in plastic manufacturing, had an increased risk of suspected MASLD, especially those of Hispanic
ethnicity . One’s risk of suspected MASLD was defined by meeting certain thresholds of ALT and BMI,
[59]
and evidence of insulin resistance. On the other hand, Chen et al. analyzed data from 6,389 adolescents (12-
17 years old) from the NHANES (1999-2014) and found a positive association between blood mercury
[60]
exposure and risk of MASLD, which was highest among non-Hispanic White individuals . Cadmium is
another heavy metal exposure previously associated with MASLD . A study from 2022 analyzing 423 soil
[61]
samples from the southern United States found that as the percentage of non-White populations increased
in an area, so did the concentration of metals in the soil including arsenic and cadmium, suggesting that
[62]
populations of minority races and ethnicities have a greater risk of exposure to these metals . These recent
studies highlight a variety of environmental exposures that may play an important, yet underappreciated
role in individuals developing MASLD, and different exposures may make certain populations more
vulnerable to MASLD than others.

Contribution of health behavioral factors to predominance of MASLD
As the global incidence of obesity and diabetes mellitus increases, so does the global incidence of MASLD .
[4]
Obesity is a major risk factor for MASLD, and both body mass index and waist circumference have been
shown to be positively correlated with the presence of MASLD and its progression [5,63] . It is well documented
that patients with MASLD in their 40s to 60s are likely to be obese . While the risk of obesity is
[64]
multifactorial, specific behavioral risk factors among patients with MASLD, including fast food
consumption, infrequent physical activity, and sedentariness, are associated with more obesity [65,66] . Several
different diets have been implicated including diets high in fat and carbohydrates, which promote liver fat
deposition via mechanisms including mitochondrial defects and endoplasmic reticulum and oxidative
stress [67,68] . Consumption of red and processed meat and MASLD have been inversely related, while
consumption of sugar-sweetened beverages is associated with a higher prevalence of MASLD, the presence
of MASH, and a higher degree of fibrosis [69,70] . Regardless of race and ethnicity, these dietary behaviors
increase one’s risk of developing MASLD, but whether they impact one race or ethnicity more so than