The prevalence of MASLD varies substantially by race and ethnicity in the United States. Using transient elastography data from the National Health and Nutrition Examination Survey (NHANES) 2017 – 2023, the overall prevalence of MASLD was estimated at 25.6%, with a prevalence of fibrosis at 11.3% [¹⁰]. Notably, between the two survey cycles, age-standardized MASLD prevalence decreased (26.8% to 23.6%), while fibrosis prevalence increased (10.4% to 12.7%), suggesting a shift toward more advanced disease in the population [¹⁰]. A summary of prevalence and fibrosis rates by race/ethnicity is presented in .

Hispanic/Latino individuals bear the highest burden. A systematic review and meta-analysis of 22 studies comprising 756,088 subjects found a pooled MASLD prevalence of 41% among U.S. Hispanic adults, with 61% prevalence of MASH and 27% prevalence of MASH-associated advanced fibrosis (defined as bridging fibrosis, stage F3 on the NASH Clinical Research Network fibrosis scale; this definition is used throughout the present review unless otherwise specified) [¹¹]. Compared with non-Hispanic adults, Hispanic adults had a relative risk of 1.50 (95% CI 1.32 – 1.69) for MASLD and 1.42 (95% CI 1.04 – 1.93) for MASH; these estimates were from multivariable-adjusted models in the constituent studies, but adjustment sets were heterogeneous across the meta-analyzed cohorts [¹¹]. The annual percentage increase in MASLD prevalence among Mexican American and other Hispanic/Latino persons was 1.9% and 1.7%, respectively, compared with 1.1% in non-Hispanic Black and non-Hispanic White populations [¹²].

In contrast, non-Hispanic Black individuals consistently demonstrate lower MASLD prevalence. In multivariable-adjusted NHANES analyses (adjusted for age, sex, BMI, diabetes, hypertension, dyslipidemia, and insurance status), both MASLD and fibrosis were inversely associated with non-Hispanic Black race/ethnicity [¹⁰]. This finding persists after controlling for metabolic risk factors and the PNPLA3 rs738409 polymorphism in biopsy cohorts, representing one of the most striking and incompletely understood paradoxes in MASLD epidemiology [¹³]. As discussed below, the apparent paradox should be interpreted with attention to ascertainment differences and to the predominantly tertiary-care setting from which the supporting biopsy cohort is drawn.

Non-Hispanic Asian individuals also demonstrate elevated MASLD risk, with NHANES data showing a significant positive association between non-Hispanic Asian race/ethnicity and MASLD on multivariable adjustment [¹⁰]. This population is particularly notable for developing MASLD at lower body mass index thresholds, a phenomenon termed "lean MASLD."

The labels "Hispanic/Latino" and "Asian" each subsume highly heterogeneous populations whose MASLD risk, PNPLA3 ancestry-allele frequency, immigration history, body composition, dietary patterns, language access, and engagement with the U.S. health system differ substantially. Within U.S. Hispanic/Latino populations, available data suggest the highest MASLD prevalence among Mexican American and Central/South American adults of high Amerindian ancestry, with progressively lower prevalence in adults of predominantly European-Iberian or Afro-Caribbean ancestry; PNPLA3 G allele frequency similarly varies by subgroup, broadly tracking the proportion of indigenous American ancestry [¹²]. Within U.S. Asian populations, MASLD risk and metabolic phenotype differ between East Asian (Chinese, Korean, Japanese), South Asian (Indian, Pakistani, Bangladeshi, Nepali, Sri Lankan), and Southeast Asian (Filipino, Vietnamese, Thai, Cambodian, Indonesian) subgroups, with South Asians displaying the highest reported prevalence of insulin resistance, abdominal adiposity at low BMI, and MASLD; published U.S. cohorts have rarely been powered to compare these subgroups directly. We discuss findings at the broader "Hispanic/Latino" and "Asian" level only because the underlying studies aggregate at this level; where subgroup-specific data are available, we say so, and where they are not (most of the time), the resulting estimates should be regarded as group-level averages that may obscure clinically meaningful subgroup differences.

Before discussing PNPLA3, it is important to distinguish three constructs that are sometimes conflated in disparity research. Self-identified race and ethnicity are social categories that capture lived social experience and structural exposure (housing, education, insurance, neighborhood resources, discrimination, language access). Genetic ancestry is a genome-derived measure of population of origin that is correlated with but not equivalent to self-identified race or ethnicity. Social determinants of health are the upstream non-medical drivers (income, education, food security, housing, neighborhood exposures, discrimination) that operate independently of either. PNPLA3 allele frequency is most properly interpreted as a marker of genetic ancestry; its higher frequency in U.S. Hispanic/Latino populations of high Amerindian ancestry helps explain part of the disease-prevalence gradient, but it does not explain (and should not be invoked to explain) structural disparities in screening, diagnosis, treatment, or transplant access. Framing population-level differences as if they reflected race or ethnicity as biological variables is scientifically inaccurate and risks reinforcing biologistic-determinist interpretations of predominantly socially structured outcomes.

With these definitions in place, genetic variation does play a real role in MASLD susceptibility and severity. Heritability accounts for approximately 50% of the variability in MASLD [²]. The most robustly validated genetic determinant is the rs738409 (I148M) variant in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), which impairs lipid-droplet remodeling and promotes hepatic fat accumulation, inflammation, and fibrogenesis [¹⁴,²].

The PNPLA3 G allele frequency, viewed as an ancestry-related variable, ranges across reference populations from approximately 47% – 52% in U.S. Hispanic/Latino samples to 15% – 23% in non-Hispanic White samples and 14% – 17% in non-Hispanic Black samples [¹²]. The G allele confers an approximately 2.3-fold greater risk of developing MASLD per allele. It is the only common variant robustly and independently associated with histologic MASLD severity in large case-only biopsy cohorts [¹²,¹⁴]. The higher frequency of the G allele in populations of high South/Central American Amerindian ancestry contributes to, but does not by itself account for, the higher MASLD burden observed in Hispanic/Latino communities; nutrition, food insecurity, occupational exposures, healthcare access, and structural barriers operate alongside genetic ancestry [¹²].

Importantly, the phenotypic expression of genetic risk factors is modulated by environmental exposures, including overall adiposity, insulin resistance, diet, and alcohol consumption [²]. Patients with PNPLA3 variants appear to require fewer metabolic risk factors before progressing to MASH, suggesting a gene-environment interaction that may be particularly relevant in populations with high ancestry-related allele frequency [¹²]. Routine genetic screening is not currently recommended; the ancestry-related allele frequencies of risk variants may become a consideration for risk stratification in the future, but should be used at the individual level, based on genotype rather than presumed group membership [¹²].

Other variants, including TM6SF2 and MBOAT7, also contribute to MASLD susceptibility. However, their effect sizes are smaller, and their associations with histologic severity are less robust than those of PNPLA3 [⁴,¹⁴]. A multiancestry evaluation of "tier 1" genetic variants across patients with biopsy-characterized MASLD found that variants in the PNPLA3-SAMM50-PARVB locus showed the most consistent associations with fibrosis severity and NAFLD activity score [¹⁴].

Multiple professional societies now recommend screening for MASLD-related fibrosis in high-risk populations. The American Diabetes Association (ADA) 2025 consensus report and the 2026 Standards of Care recommend the Fibrosis-4 Index (FIB-4) as the most cost-effective initial screening strategy for people with prediabetes and cardiometabolic risk factors or with type 2 diabetes [¹⁸,⁴]. The AASLD and the AACE similarly endorse a staged approach using FIB-4 as a first-line tool, followed by imaging-based assessments such as vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE) for those with indeterminate or elevated scores [¹⁹,²⁰,²¹].

Despite these recommendations, clinicians consistently underestimate the prevalence of at-risk MASH and do not implement appropriate screening strategies, resulting in sparse referral to specialists and inadequate prescription of medications with potential efficacy [¹⁸]. This pattern of underdiagnosis is compounded by the fact that at-risk MASH with clinically significant fibrosis (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\geq$\end{document}≥F2) is frequently observed with plasma aminotransferases below the commonly used cutoff of 40 U/L [¹⁸].

A critical and underappreciated disparity lies in the differential performance of noninvasive screening tools across racial and ethnic groups. In a single prospective study of 244 adults with biopsy-proven MASLD, MRE and VCTE exhibited significantly lower accuracy for detecting significant fibrosis in Hispanic versus non-Hispanic participants (AUROC: MRE, 0.87 vs. 0.98, p = 0.01; VCTE, 0.78 vs. 0.92, p = 0.02) [²²]. Clinical care algorithms yielded high false-negative rates among Hispanic participants in that cohort: 14% with low-risk FIB-4 and 21% with low-risk VCTE had advanced fibrosis on biopsy [²²].

FIB-4 is not a race-neutral biological measurement: it is a composite of age, AST, ALT, and platelet count, and each of these components varies systematically by population. The age term contributes substantially to the FIB-4 value and, with standard cutoffs (<1.3 to rule out, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\geq$\end{document}≥2.67 to refer for further assessment), tends to under-classify younger adults and over-classify older adults regardless of underlying liver disease; this may particularly affect younger Hispanic/Latino patients with high genetic-ancestry risk who can have clinically significant fibrosis at younger ages. Coexistent type 2 diabetes affects aminotransferase distributions and modifies the relationship of FIB-4 to histologic fibrosis. Platelet count varies by population, comorbidity, and certain medications (including some antihypertensives and antiretrovirals). AST and ALT distributions are influenced by sex, body composition, muscle mass, recent exercise, and alcohol intake. Population-level shifts in any of these components can change the operating characteristics of FIB-4 in ways that are not captured by race/ethnicity stratification alone. Implementation pathways that propose race- or ethnicity-specific FIB-4 thresholds should therefore be paired with age- and comorbidity-specific calibration; thresholds that vary by self-identified group risk imply biologic difference where age and comorbidity structure is the real driver.

These findings have direct clinical implications. Standard noninvasive test cutpoints were derived from predominantly non-Hispanic populations and may be insufficiently sensitive for Hispanic individuals, who carry the highest disease burden [²²]. In the derivation cohort, optimized cutpoints of 2.73 kPa for MRE and 6.9 kPa for VCTE were identified for detecting significant fibrosis in Hispanic populations, and these findings were externally evaluated in a Latin American cohort [²²]. A proposed pathway incorporating adjusted FIB-4 and secondary assessment thresholds for Hispanic/Latino patients has been outlined, but these population-specific thresholds should be regarded as investigational. Broader prospective validation in diverse, community-based U.S. populations is required before they are adopted into routine clinical practice, and current professional society guidelines (AASLD, AACE, ADA) do not yet endorse race- or ethnicity-specific cutpoints [¹²].

Lowering screening thresholds – whether universally or for specified subgroups – has consequences beyond improved sensitivity. A more permissive FIB-4 cutoff increases the number of patients referred for second-line VCTE or MRE assessment; in U.S. settings where VCTE and especially MRE capacity is concentrated in tertiary centers, this translates directly into longer wait times, higher per-encounter cost, and (paradoxically) potentially less access for the very populations the change is meant to serve. The same change increases the number of false-positive results that prompt specialist referral, additional imaging, possible biopsy, and patient anxiety – a non-trivial harm that must be weighed against the gain in true positives. Hepatology capacity in safety-net systems is already strained. An equity-focused screening strategy must therefore be implementable, not only clinically valid; we suggest that any move toward population-specific thresholds be accompanied by health-system modeling of the projected change in referral volume, by investment in community-based VCTE infrastructure, and by primary-care decision-support tools that distinguish high-yield from low-yield referrals.

One of the most-cited findings in MASLD epidemiology is the paradoxically lower prevalence of MASLD and advanced fibrosis in non-Hispanic Black individuals, despite a higher burden of metabolic risk factors in some studies. In a NASH Clinical Research Network biopsy cohort of 109 non-Hispanic Black and 1,910 non-Hispanic White adults with biopsy-proven NAFLD, non-Hispanic Black individuals had similar NAFLD activity scores (4.4 vs. 4.3) and proportions with definite MASH (59% vs. 58%) but significantly lower rates of advanced fibrosis (22% vs. 34%, p = 0.01) and cirrhosis (4.6% vs. 12.1%, p = 0.01) [¹³]. After multivariable adjustment for clinical risk factors and PNPLA3 genotype, non-Hispanic Black race remained independently associated with lower odds of advanced fibrosis (adjusted OR 0.48, 95% CI 0.27 – 0.86) [¹³].

However, among those non-Hispanic Black individuals who did develop advanced fibrosis, the NAFLD activity score (5.6 vs. 4.9, p = 0.01) and lobular inflammation grade (2.2 vs. 1.7, p = 0.002) were significantly higher than in non-Hispanic White counterparts with advanced fibrosis [¹³]. This pattern has been interpreted as evidence of a fundamentally different relationship between necroinflammation and fibrogenesis. We urge caution with that inference: the cohort is small (n = 109 non-Hispanic Black participants), drawn from tertiary-referral biopsy practices, and subject to substantial ascertainment bias (see Selection, Ascertainment, and Referral Bias, below). The pattern may equally well reflect differential referral for biopsy, differential delay from disease onset to evaluation, or unmeasured confounding.

Despite lower MASLD prevalence, non-Hispanic Black patients with cirrhosis – in studies of all etiologies – face worse outcomes. In a large metropolitan cohort study of 11,277 patients with cirrhosis from all causes (not restricted to MASH cirrhosis), Black patients had the highest rate of all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (p <0.001 for all) [²⁵]. In multivariable competing-risk analysis (adjusted for age, sex, MELD score, insurance, neighborhood deprivation, and primary cirrhosis etiology), Black patients had a 26% increased hazard of liver-related death (sHR 1.26, 95% CI 1.15 – 1.38) [²⁵]. Because that cohort included patients with cirrhosis from viral hepatitis, alcohol-associated liver disease, and other causes in addition to MASH, these findings should not be interpreted as MASLD/MASH-specific outcome data. MASH-specific outcome data in non-Hispanic Black patients remain limited, and the contribution of disparities in care access, comorbidity burden, and competing causes of death to the worse cirrhosis outcomes observed in this population cannot be disentangled from any MASLD-specific biology in the existing literature.

Resmetirom, a liver-directed thyroid hormone receptor beta (THR-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\beta$\end{document}β) selective agonist, received FDA accelerated approval in March 2024 based on the MAESTRO-NASH trial [⁶]. In this phase 3 trial, 966 patients with biopsy-proven MASH and F1 – F3 fibrosis were randomized to resmetirom 80 mg, 100 mg, or placebo for 52 weeks. MASH resolution without worsening of fibrosis was achieved in 25.9% (80 mg) and 29.9% (100 mg) versus 9.7% (placebo), while fibrosis improvement without worsening of MASH was achieved in 24.2% (80 mg) and 25.9% (100 mg) versus 14.2% (placebo) (p <0.001 for all comparisons) [⁶].

The trial population was demographically homogeneous and underrepresented racial and ethnic minorities relative to the U.S. MASLD-affected population: 89% White, 21% Hispanic, 3% Asian, and only 2% Black or African American [²⁸]. This severe underrepresentation of Black patients limits the generalizability of efficacy and safety data to this population. Current practice guidance on resmetirom use in noncirrhotic MASH does not address race- or ethnicity-specific considerations for patient selection or monitoring.

The cost of resmetirom presents a significant barrier to equitable access. The average annual wholesale price is approximately $47,000 – $57,670, and the medication may not be covered by health insurance or may require prior authorization [²⁹]. An economic evaluation found that at a price of $19,011/year, resmetirom was not cost-effective compared with standard of care at a $100,000/QALY willingness-to-pay threshold [²⁹]. At the current wholesale price, the incremental cost-effectiveness ratio was estimated at $140,134/QALY [²⁹]. In comparison, off-label treatments such as pioglitazone are available generically at a small fraction of the cost of FDA-approved MASH therapies.

Semaglutide received accelerated FDA approval in August 2025 for the treatment of noncirrhotic MASH with moderate to advanced fibrosis (F2 – F3) based on the phase 3 ESSENCE trial [⁷]. In the first 800 participants, 72 weeks of semaglutide 2.4 mg/week achieved resolution of MASH without worsening of fibrosis in 62.9% versus 34.3% with placebo (p <0.001), and improvement in fibrosis without worsening of MASH in 36.8% versus 22.4% (p <0.001) [⁷,⁸].

The ESSENCE trial enrolled a geographically more diverse population than MAESTRO-NASH, with participants from Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%) (Table 2) [⁸]. However, the trial investigators themselves acknowledged limitations including the small number of Black patients and a lack of data regarding genetic polymorphisms as determinants of therapeutic response [⁸]. The trial population was 67.5% White and 57.1% female [⁸].

Issuing an FDA-approved MASH therapy is not the same as a patient actually receiving it. The pre-prescription pathway in the United States involves several sequential steps, each of which is associated with documented or plausible disparities. (1) Risk identification in primary care depends on systematic application of cardiometabolic criteria; underdiagnosis is well-documented and is greater in patients with low health literacy, limited English proficiency, and intermittent care engagement. (2) Fibrosis assessment with FIB-4 is inexpensive but is not routinely ordered; second-line VCTE or MRE requires referral and equipment that is unevenly distributed (see Barriers to Screening Implementation). (3) Specialist referral to hepatology or to a metabolic-MASH program adds a wait of weeks to months and depends on insurance network, transportation, and local capacity. (4) Confirmation of eligibility requires documentation of noncirrhotic F2 – F3 fibrosis and exclusion of cirrhosis; some payers also require demonstration of failed lifestyle intervention. (5) Prior authorization is universal for resmetirom and is increasingly common for GLP-1 receptor agonists [³⁰]; approval rates vary by payer and have been shown in obesity prescribing data to be lower for patients in higher-deprivation neighborhoods [³¹]. (6) Treatment initiation requires that the patient can afford copays (typically $20 – $400/month with insurance, full wholesale cost without it) and can manage the route of administration (oral resmetirom vs. injectable semaglutide). (7) Monitoring and follow-up (addressed below) introduces further demands. Loss at any of these steps disproportionately affects patients with limited insurance, limited English, rural residence, or precarious work schedules. Disparities in actual MASH-pharmacotherapy use will therefore exceed disparities at any single step, and reporting only "prescribed/not prescribed" undercounts the problem.

The cost discussion has tended to dominate the equity literature on new MASH therapies, but ongoing monitoring requirements and adverse-event management are themselves potential equity barriers. Resmetirom requires baseline and periodic monitoring of liver biochemistries, lipid panel, thyroid function (TSH and free T4), and assessment for drug interactions; gastrointestinal adverse effects (diarrhea, nausea) are common in the first weeks of therapy and may require clinical contact for dose adjustment [²⁸,⁶]. Subcutaneous semaglutide requires patient education in self-injection, gradual dose titration to manage nausea and vomiting, and longitudinal contact for safety monitoring (including pancreatitis surveillance and assessment for gallbladder disease) [⁷,⁸]. Each of these touchpoints presupposes reliable access to scheduled care, a phone or portal connection to the prescribing clinician, and the ability to leave work for appointments. Patients in safety-net systems and those facing transportation, language, or scheduling barriers are predictably more likely to miss monitoring visits, to discontinue therapy due to unaddressed side effects, or to fail to obtain dose adjustments. We therefore argue that equity-focused implementation of MASH pharmacotherapy must include (a) pharmacy-based or telehealth-delivered titration support, (b) translated dosing and side-effect material, (c) explicit accommodation for patients without reliable transportation, and (d) systematic measurement of disparities in persistence, not only in initiation.

Clinicians should: (1) universally apply FIB-4 screening for patients with type 2 diabetes, prediabetes with cardiometabolic risk factors, or obesity, regardless of race or ethnicity, per ADA and AACE guidance [¹⁸,⁴,¹⁹]; (2) when interpreting FIB-4 results, account for age and comorbidity rather than relying on a single fixed cutoff in all patients (see Differential Performance of Noninvasive Tests); (3) refer indeterminate or elevated FIB-4 results for VCTE or MRE per existing pathways and document and address barriers to imaging access; (4) screen patients with MASLD for food insecurity, transportation barriers, language preference, insurance coverage, and depression as part of routine assessment [²³,²⁴]; (5) discuss the access pathway for resmetirom and semaglutide candidly with eligible patients, including prior authorization, copay, monitoring requirements, and pharmacy logistics; and (6) refer eligible patients to manufacturer patient-assistance and copay-support programs.

Health systems and payers should: (1) invest in community-based VCTE capacity in safety-net systems serving high-prevalence populations rather than concentrating advanced imaging at tertiary centers [²⁴]; (2) integrate FIB-4 ordering into primary-care and endocrinology workflows with decision support that surfaces social-needs screening alongside the laboratory result; (3) reduce prior-authorization friction for FDA-approved MASH therapies, particularly in Medicaid and Medicare Advantage [³⁰]; (4) expand pharmacy- and telehealth-delivered titration and adherence support for resmetirom and semaglutide, with translated materials; (5) develop transplant-center quality metrics that include race/ethnicity- and sex-stratified time-to-listing, time-to-transplant, and post-transplant survival [²⁷,²⁶]; and (6) require structured measurement and public reporting of disparities in MASLD diagnosis, treatment initiation, treatment persistence, and outcomes.

The following are proposed for further investigation and are not recommended for routine clinical use until validated: (1) prospective validation of population-specific FIB-4, VCTE, and MRE thresholds in diverse, community-based U.S. cohorts with explicit subgroup reporting by Hispanic/Latino subgroup (Mexican American, Central/South American, Caribbean Hispanic) and Asian subgroup (East/South/Southeast Asian) [²²]; (2) PNPLA3- and genetic-ancestry-stratified efficacy and safety analyses for resmetirom, semaglutide, and emerging agents in adequately powered trials or registries [¹²]; (3) equity-weighted cost-effectiveness analyses of MASH pharmacotherapy that incorporate downstream costs of untreated MASH in high-risk populations [²⁹]; (4) mechanistic studies of the non-Hispanic Black biopsy-cohort paradox that control for ascertainment and referral effects [¹³]; (5) implementation-science evaluations of community-health-worker, pharmacist-led, and culturally tailored care models for MASLD [¹²]; and (6) intersectional disparity research that simultaneously stratifies by race/ethnicity, sex, age, rurality, insurance, and language. The FDA’s 2024 final guidance on Diversity Action Plans provides a regulatory framework that supports the trial-side components of this agenda; sponsors are now expected to submit prospective enrollment goals stratified by race, ethnicity, sex, and age for most pivotal trials. We suggest, as expert opinion, that pre-specified subgroup analyses by race, ethnicity, and PNPLA3 genotype be planned for pivotal MASH trials and that trials be powered (or, when this is infeasible, descriptively reported) to permit meaningful interpretation of these subgroups; mandating such analyses for every pivotal trial would, however, be a policy choice for regulators rather than an evidence-based requirement.