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Page 6 of 17 Gulati et al. Metab Target Organ Damage 2024;4:9 https://dx.doi.org/10.20517/mtod.2023.45

with United States-born Asians. In addition, Hispanic and White patients are more likely to be diagnosed
[34]
with cirrhosis at an age younger than 40 years compared to non-Hispanic Black patients . A study utilizing
the NIS analyzed all adult hospitalizations from 2016 to 2018 with MASH and found that non-Hispanic
Black patients were less likely to have cirrhosis and liver disease-related complications, but had overall
worse hospital mortality, longer lengths of stay, and higher hospital costs than White patients . Multiple
[35]
studies have been done investigating the significance of racial and ethnic disparities in patients undergoing
liver transplantation for MASLD-related HCC. Couto et al. found that Hispanic patients were at increased
risk for needing liver transplant for MASLD-related HCC, which may be attributed to Hispanic individuals
with HCC having more co-morbidities such as diabetes and hypertension than non-Hispanic individuals
[36]
with HCC . It is important to note that while the impact of MASLD on certain populations’ risks of other
associated diseases such as colorectal cancer has been established thoroughly, there is a lack of research on
these phenomena in certain racial and ethnic groups . Further research is needed to determine whether
[37]
MASLD impacts all populations similarly.

An additional limitation results from significant racial and ethnic disparity around the detection of MASLD.
Although liver biopsy is the gold standard for diagnosis and assessment of the severity of MASLD, its use is
limited due to its risks, invasiveness, and cost . Due to this, many noninvasive clinical scores including
[38]
MASLD fibrosis score (NFS), BARD, Fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio
index (APRI) have been developed and are utilized regularly to predict advanced fibrosis in patients with
MASLD. Some of these scores can efficiently use demographic and laboratory test information from
patients to risk-stratify patients with MASLD and help guide clinical decision-making. A study published in
2021 investigated the performance of the NFS, BARD, FIB-4, and APRI in a predominantly Hispanic patient
population and found that while the area under the receiver operating characteristic curve (AUROC) was
similar for these scores in Hispanic and non-Hispanic White populations, they had uniformly lower
negative predictive values among the Hispanic study population . This study suggests that widely used
[38]
non-invasive fibrosis scores may not accurately rule out advanced liver fibrosis in Hispanic populations,
most likely due to differences in the underlying prevalence of disease. Studies have also found disparities in
MASLD diagnostic markers for other ethnicities. De Silva et al. noted that NFS, APRI, FIB-4, and AST/ALT
ratio were less sensitive for detecting advanced liver fibrosis in South Asian populations compared to White
populations . These studies highlight disparities in detecting and staging MASLD, which may contribute
[39]
to our understanding of its epidemiology.

POTENTIAL CONTRIBUTORS OF RACIAL AND ETHNIC DISPARITIES IN MASLD
After recognizing the existence of racial and ethnic disparities in the prevalence, severity, and natural
history of MASLD in the United States, an important next step in decreasing these disparities is discovering
why they exist. Based on available evidence, racial and ethnic disparities in MASLD are likely multifactorial,
resulting from genetics, environmental exposures, diet/physical activity, healthcare factors including access
to primary care and sub-specialists, provider bias, and socioeconomic disparities, including those that
influence health-promoting activities such as exercise [Figure 1] [Table 2]. While the relative contribution
of each factor is unclear, they appear interconnected in promoting the development and progression of
MASLD. The importance of each factor likely varies by race and ethnicity and over one’s lifetime. The
purpose of presenting various potential factors that contribute to these disparities within MASLD is to
promote discussion regarding efforts and initiatives that can be made to decrease the burden of MASLD
within specific populations that are at higher risk for the disease than others.

Contribution of genetics to racial and ethnic disparities within MASLD
Multiple genome-wide association studies (GWAS) have discovered and validated specific genetic