Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), represent significant and growing health concerns globally [
1]. In the United States, these conditions are the most common chronic liver diseases, affecting approximately 75–100 million Americans [
2]. However, the burden of these conditions and their outcomes are not uniformly distributed across different racial and ethnic groups. Understanding the underlying factors and their interplay is crucial for managing and improving patient outcomes, especially given the racial and ethnic disparities in healthcare access and quality. This editorial discusses the disparities in MASLD outcomes among racial and ethnic groups, emphasizing the importance of addressing social determinants of health (SDOH) and implementing culturally sensitive interventions for effective management and prevention.
Genetic background and environmental factors in MASLD
The variability in MASLD outcomes among different racial and ethnic groups can be attributed to a combination of genetic, environmental, and socioeconomic factors. Genetic polymorphisms such as
PNPLA3, TM6SF2, and
MBOAT7 significantly influence NAFLD susceptibility and progression with varying prevalence among racial and ethnic groups [
3]. For instance, the
PNPLA3 I148M variant is more prevalent among Hispanics, contributing to their higher susceptibility to NAFLD compared to non-Hispanic Whites and Blacks [
4]. Additionally, populations with the same genetic variant show a higher propensity for developing severe liver disease, highlighting the role of genetic differences in disease progression and outcomes [
5].
Environmental factors, including diet, physical activity, and access to healthcare, also play critical roles. SDOH, such as income, education, and neighborhood conditions, profoundly impact MASLD prevalence and outcome. Hispanic populations often experience higher levels of adverse SDOH [
6], which exacerbate their risk of developing severe MASLD [
2]. Limited access to healthy foods, lower levels of physical activity due to unsafe neighborhoods, and reduced healthcare access due to social and economic barriers contribute to worse health outcomes.
Disparities in MASLD outcomes
Nguyen et al. [
7] recently published a paper indicating significant disparities in NAFLD outcomes among different racial and ethnic groups using longitudinal real-world data. This study found that Black patients with NAFLD face the highest risk of overall and non-liver-related mortality, followed by Hispanic patients, while Asian patients exhibit the lowest risk for all adverse outcomes compared to white patients [
7]. These findings highlight the complex interplay of genetic predisposition, environmental exposures, and SDOH in shaping MASLD outcomes.
Black patients, despite having a lower prevalence of NAFLD, tend to have worse outcomes once the disease is established [
8]. Studies suggest that Black patients with NAFLD are disproportionately affected by comorbid conditions such as obesity, prediabetes, type 2 diabetes, hypertension, and dyslipidemia, all of which contribute to increased mortality rates [
8,
9]. Moreover, structural racism and socioeconomic disadvantages limit their access to early diagnosis, treatment, and preventive care. This disparity is further compounded by systemic biases within healthcare systems that can result in less aggressive treatment and follow-up care for minority patients.
Hispanic patients, on the other hand, exhibit the highest prevalence of NAFLD, often linked to higher rates of obesity and diabetes in this population [
2,
10]. However, the progression to severe liver disease and related mortality is also significant among Hispanics, necessitating targeted interventions [
2]. The cultural context, including dietary habits and lifestyle factors, plays a crucial role. For instance, traditional diets high in carbohydrates and fats can contribute to higher rates of obesity and metabolic syndrome, leading to MASLD. Addressing these dietary patterns through culturally sensitive dietary interventions can be an effective strategy in this population.
Cardiovascular mortality and MASLD
One critical aspect of managing NAFLD is recognizing that the leading cause of death in these patients is not liverrelated but cardiovascular. This has led to the proposal of MASLD as a more comprehensive term that better captures the metabolic dysfunctions associated with fatty liver disease [
1]. MASLD emphasizes the role of metabolic syndrome components such as obesity, insulin resistance, and dyslipidemia, which are prevalent across various racial and ethnic groups but manifest differently [
11].
Studies show that patients with MASLD have higher allcause and cardiovascular mortality compared to those with NAFLD [
12]. This further underscores the need for integrated care approaches that address both liver and cardiovascular health, particularly in high-risk racial and ethnic populations. Managing metabolic syndrome through lifestyle modifications and pharmacotherapy can significantly reduce the risk of both liver-related and cardiovascular outcomes [
13,
14].
Precision medicine and culturally sensitive interventions
Addressing racial and ethnic disparities in MASLD outcomes requires a precision medicine approach that considers the unique genetic, environmental, and social factors affecting different populations [
15]. Culturally sensitive interventions are crucial for improving health outcomes in these groups. For example, tailored lifestyle modification programs that respect cultural dietary preferences and incorporate community-based support can enhance engagement and effectiveness [
13].
Healthcare providers should be trained to understand and address the specific needs of diverse populations. This includes not only clinical knowledge but also cultural competence to build trust and improve patient-provider communication. Using culturally relevant materials and involving community health workers who share similar backgrounds with the patients can improve outreach and adherence to treatment plans [
16]. Policymakers must also work towards reducing structural barriers to healthcare access and implementing policies that address broader SDOH, such as improving education, housing, and economic opportunities for marginalized communities [
17].
Moreover, precision medicine involves using genetic information to tailor treatments. Genetic testing can identify individuals at higher risk for severe MASLD and allow for early interventions. For instance, knowing that a Hispanic patient with obesity carries the
PNPLA3 I148M variant can prompt more aggressive lifestyle interventions and monitoring [
18]. This personalized approach ensures that interventions are both effective and efficient, addressing the root causes of disparities in MASLD outcomes [
19].
Conclusion
The disparities in MASLD outcomes among different racial and ethnic groups are a complex issue influenced by genetic, environmental, and social factors. Black and Hispanic patients are at higher risk for adverse outcomes, including higher mortality rates, compared to White and Asian patients [
7]. Addressing these disparities requires a multifaceted approach that includes precision medicine, culturally sensitive interventions, and policies aimed at improving SDOH. By doing so, we can move towards more equitable healthcare and better outcomes for all patients with MASLD.
FOOTNOTES
-
Authors’ contribution
Conception or design of the work: JHB. Data collection: JHB. Data analysis and interpretation: JHB. Drafting the article: JHB. Critical revision of the article: JHB. Final approval of the version: JHB.
-
Conflicts of Interest
The author has no conflicts to disclose.
Abbreviations
metabolic dysfunction-associated steatotic liver disease
non-alcoholic fatty liver disease
social determinants of health
REFERENCES
- 1. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol 2020;73:202-209.
- 2. Rich NE, Oji S, Mufti AR, Browning JD, Parikh ND, Odewole M, et al. Racial and ethnic disparities in nonalcoholic fatty liver disease prevalence, severity, and outcomes in the United States: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018;16:198-210.e2.
- 3. Longo M, Meroni M, Paolini E, Erconi V, Carli F, Fortunato F, et al. TM6SF2/PNPLA3/MBOAT7 loss-of-function genetic variants impact on NAFLD development and progression both in patients and in in vitro models. Cell Mol Gastroenterol Hepatol 2022;13:759-788.
- 4. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461-1465.
- 5. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011;53:1883-1894.
- 6. Ochoa-Allemant P, Marrero JA, Serper M. Racial and ethnic differences and the role of unfavorable social determinants of health across steatotic liver disease subtypes in the United States. Hepatol Commun 2023;7:e0324.
- 7. Nguyen VH, Le I, Ha A, Le RH, Rouillard NA, Fong A, et al. Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal realworld study. Clin Mol Hepatol 2023;29:1002-1012.
- 8. Nguyen VH, Le MH, Cheung RC, Nguyen MH. Differential clinical characteristics and mortality outcomes in persons with NAFLD and/or MAFLD. Clin Gastroenterol Hepatol 2021;19:2172-2181.e6.
- 9. Kardashian A, Serper M, Terrault N, Nephew LD. Health disparities in chronic liver disease. Hepatology 2023;77:1382-1403.
- 10. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73-84.
- 11. Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020;158:1999-2014.e1.
- 12. Kim KS, Hong S, Ahn HY, Park CY. Metabolic dysfunction-associated fatty liver disease and mortality: A population-based cohort study. Diabetes Metab J 2023;47:220-231.
- 13. Younossi ZM, Zelber-Sagi S, Henry L, Gerber LH. Lifestyle interventions in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2023;20:708-722.
- 14. Jang H, Kim Y, Lee DH, Joo SK, Koo BK, Lim S, et al. Outcomes of various classes of oral antidiabetic drugs on nonalcoholic fatty liver disease. JAMA Intern Med 2024;184:375-383.
- 15. Lazarus JV, Mark HE, Anstee QM, Arab JP, Batterham RL, Castera L, et al. Advancing the global public health agenda for NAFLD: a consensus statement. Nat Rev Gastroenterol Hepatol 2022;19:60-78.
- 16. He J, Bundy JD, Geng S, Tian L, He H, Li X, et al. Social, behavioral, and metabolic risk factors and racial disparities in cardiovascular disease mortality in U.S. adults: An observational study. Ann Intern Med 2023;176:1200-1208.
- 17. Lazarus JV, Anstee QM, Hagström H, Cusi K, Cortez-Pinto H, Mark HE, et al. Defining comprehensive models of care for NAFLD. Nat Rev Gastroenterol Hepatol 2021;18:717-729.
- 18. Stender S, Kozlitina J, Nordestgaard BG, Tybjærg-Hansen A, Hobbs HH, Cohen JC. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nat Genet 2017;49:842-847.
- 19. Eslam M, George J. Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology. Nat Rev Gastroenterol Hepatol 2020;17:40-52.
Citations
Citations to this article as recorded by
- Prevalence and risk factors for metabolic dysfunction–associated steatotic liver disease in Sweden: Insights from the SCAPIS cohort
Oumarou Nabi, Jonas Spaak, Göran Bergström, Gunnar Engström, Carl Johan Östgren, Andrei Malinovschi, Joel Kullberg, Anders Blomberg, Tomas Jernberg, Daniel P. Andersson, Hannes Hagström
Journal of Internal Medicine.2026; 299(4): 481. CrossRef - Resveratrol dual efficacy in high-altitude hypoxia and NAFLD: inhibits ferroptosis by modulating key proteins, including HIF-1α, ACSL4, and TfR1
Minghui Zhao, Hongfang Mu, Qian Ji, Jiale Song, Fuyixuan Zheng, Tianlong Liu, Wenbin Li, Rong Wang
Phytomedicine.2026; 153: 157992. CrossRef - Association of serum uric acid and serum uric acid/creatinine ratio with metabolic dysfunction-associated fatty liver disease in young adults: a retrospective study
Yue Li, Zixian Li, Siyu Wu, Ling Cao, Beibei Qian, Junxian Tao, Zhimin Qian, Li Xie, Xiaoli Cai, Xiaofang Sun, Ying Li, Zhenwen Zhang, Caifeng Yan, Dunmin She
BMC Endocrine Disorders.2026;[Epub] CrossRef - MASLD In Children - A Distinct Phenotype?
Pervej Alom Barbhuiya, Manash Pratim Pathak
Current Obesity Reports.2026;[Epub] CrossRef - Hepatic Outcomes in Lean Versus Nonlean Metabolic Dysfunction–Associated Steatotic Liver Disease: Propensity‐Matched Cohort Study
Rishi Chowdhary, Manjeet Kumar Goyal, Ashita Rukmini Vuthaluru, Megh Patel, Tanisha Sehgal, Kirti Arora, Rahul Chowdhary, Varun Mehta, Akash Batta, Omesh Goyal
Hepatology Research.2026;[Epub] CrossRef - Use of Hepatoscope 2DTE for non-invasive assessment of liver stiffness among Mexican immigrant adults in a community-based setting
Edgar A. Villavicencio, Cindy Serdjebi, Adriana Maldonado, Estefania Ochoa Mora, Adrien Besson, Naim Alkhouri, David O. Garcia
Clinics and Research in Hepatology and Gastroenterology.2025; 49(5): 102581. CrossRef - Frailty and MASLD in the Arab region: An urgent call for regional clinical and public health strategies
Mohamed El-Kassas, Khalid Alswat, Asma Labidi, Maen Almattooq, Doaa Zakaria, Nabil Debzi, Faisal M Sanai, Mohamed Elbadry, Ali Tumi, Imam Waked, Abdel-Naser Elzouki, Khalid M. AlNaamani
Arab Journal of Gastroenterology.2025; 26(4): 315. CrossRef - Dietary Interventions in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review of Evidence, Mechanisms, and Translational Challenges
Alejandra Paredes-Marin, Yulu He, Xiaotao Zhang
Nutrients.2025; 17(21): 3491. CrossRef - Research and clinical trial design in patients with metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD): a narrative review
Pedro Acuña, Omar Albhaisi, Francisco Idalsoaga, Naim Alkhouri, Mazen Noureddin, Luis Antonio Díaz, Juan Pablo Arab
Metabolism and Target Organ Damage.2025;[Epub] CrossRef - Correspondence to editorial on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study”
Vy H. Nguyen, Mindie H. Nguyen
Clinical and Molecular Hepatology.2024; 30(4): 1000. CrossRef - Reply to correspondence on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study”
Jae Hyun Bae
Clinical and Molecular Hepatology.2024; 30(4): 1047. CrossRef
