Global Burden of MASLD Grows as Experts Highlight Comorbidities and Racial Disparities

Key facts

The analysis from Healthgrades examines the growing recognition of metabolic dysfunction-associated steatotic liver disease (MASLD) as a worldwide public health priority, detailing how its intersection with comorbid conditions creates distinct challenges for racially diverse patient populations. Affecting an estimated 38 percent of adults globally, MASLD occurs when excessive fat accumulates within liver cells, known clinically as hepatic steatosis, in individuals who consume little to no alcohol. Under the updated diagnostic framework established by international liver organizations, a formal MASLD diagnosis requires the presence of hepatic fat alongside at least one of five core metabolic risk factors: elevated body mass index or waist circumference, impaired fasting blood glucose or diagnosed type 2 diabetes, high blood pressure, elevated plasma triglycerides, or decreased high-density lipoprotein cholesterol levels.

The findings highlight that MASLD rarely exists in isolation. Patients with the disease frequently present with multiple metabolic comorbidities, which act synergistically to accelerate liver tissue damage. When hepatic fat accumulation causes inflammation and cellular injury, the condition advances to metabolic dysfunction-associated steatohepatitis (MASH). MASH can trigger progressive liver scarring, or fibrosis, eventually leading to cirrhosis, liver failure, and primary liver cancer (hepatocellular carcinoma).

The presentation and outcome of MASLD vary significantly across racial and ethnic lines due to a combination of biological, genetic, and socio-economic factors, according to the reporting. In the United States, Hispanic individuals exhibit the highest prevalence of hepatic steatosis among major racial and ethnic groups. Genetic research has linked this heightened risk to a higher frequency of the rs738409 single nucleotide polymorphism in the PNPLA3 gene, which impairs normal lipid breakdown in liver cells. Conversely, non-Hispanic Black individuals display relatively lower average intrahepatic triglyceride levels, yet suffer disproportionately high rates of metabolic complications such as severe hypertension and insulin resistance. This clinical mismatch can lead to underdiagnosis or delayed screening in Black patients when primary care clinicians rely solely on standard liver enzyme tests or conventional fat thresholds. Additionally, Asian populations often develop MASLD at lower body mass index thresholds—a phenomenon known as lean MASLD—reflecting ethnic variations in visceral fat distribution and metabolic sensitivity.

Why it matters

The escalating prevalence of MASLD presents profound public health, clinical, and economic implications globally. Chronic liver disease has rapidly transitioned from being driven primarily by viral hepatitis B and C to being overwhelmingly driven by metabolic dysfunction. Because early-stage hepatic steatosis is largely asymptomatic, millions of individuals remain undiagnosed until advanced liver fibrosis or end-stage liver disease develops, creating severe strains on specialized health services and organ transplant networks.

Furthermore, cardiovascular disease—not liver failure—remains the leading cause of death among patients diagnosed with MASLD. The systemic vascular inflammation and insulin resistance associated with metabolic liver disease significantly increase the incidence of myocardial infarction, stroke, and heart failure. The presence of type 2 diabetes doubles the risk of progression from simple steatosis to MASH and advanced fibrosis, creating a dangerous feedback loop between endocrine and hepatic dysfunction.

For healthcare systems and insurers, managing MASLD and its associated comorbidities incurs substantial financial costs, encompassing frequent hospitalizations, routine imaging, long-term pharmacological management, and liver transplants. Addressing racial and ethnic disparities in MASLD care is critical to closing broader health equity gaps. Underserved communities often face reduced access to specialized diagnostic tools—such as transient elastography—and encounter delays in accessing emerging therapeutic interventions, threatening to widen existing health outcome disparities as advanced treatments enter the commercial market.

The current clinical understanding of MASLD is the result of a deliberate, multi-year effort by the global medical community to refine disease definitions and eliminate stigmatizing vocabulary. In June 2023, a consensus statement published jointly by the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the Latin American Association for the Study of the Liver (ALEH) officially introduced the term steatotic liver disease (SLD) as an overarching umbrella. Within this new structure, nonalcoholic fatty liver disease (NAFLD) was formally renamed metabolic dysfunction-associated steatotic liver disease (MASLD), while nonalcoholic steatohepatitis (NASH) became metabolic dysfunction-associated steatohepatitis (MASH).

The nomenclature shift was designed to achieve two major objectives: replacing negative terms such as nonalcoholic and fatty with affirmative, patient-centric medical descriptors, and establishing clear diagnostic criteria centered on positive metabolic indicators rather than the exclusion of alcohol consumption. The panel also created a distinct subcategory termed MetALD to classify individuals with MASLD who consume greater amounts of alcohol per week than standard MASLD thresholds allow, but less than the thresholds defining pure alcohol-related liver disease (ALD).

Historically, clinical management of MASLD relied almost exclusively on lifestyle interventions, including calorie-restricted diets, Mediterranean dietary patterns, increased physical activity, and targeted weight loss goals of 7 to 10 percent of total body weight, which can promote fibrosis regression. However, sustained weight loss through lifestyle modifications alone remains difficult for many patients to achieve and maintain long-term.

The therapeutic landscape experienced a major shift in March 2024 when the U.S. Food and Drug Administration approved resmetirom, marketed under the brand name Rezdiffra, developed by Madrigal Pharmaceuticals. Resmetirom became the first targeted prescription medication approved for adults with non-cirrhotic MASH featuring moderate-to-advanced liver scarring (fibrosis stages F2 and F3). Concurrent advancements in metabolic medicine, particularly the widespread clinical use of glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/GIP receptor agonists initially developed for type 2 diabetes and obesity management, have shown notable secondary benefits in reducing liver fat and systemic inflammation.

Reaction

Medical organizations, hepatology researchers, and patient advocacy groups have welcomed the standardized MASLD framework, viewing it as a pivotal step toward integrated cardiovascular, metabolic, and hepatic care. Professional societies, including the American College of Physicians and the American Diabetes Association, have increasingly advocated for primary care clinicians and endocrinologists to perform proactive MASLD screening among high-risk patient groups, such as adults living with type 2 diabetes or persistent metabolic syndrome.

Hepatology specialists emphasize the necessity of transitioning routine screening away from invasive liver biopsies toward non-invasive testing modalities. The use of simple blood-based scoring systems, such as the Fibrosis-4 (FIB-4) index, alongside point-of-care transient elastography (FibroScan), is widely recommended to identify patients at low risk who can be managed in primary care versus those requiring rapid referral to specialized liver centers.

At the same time, health equity scholars and patient advocacy coalitions have called for targeted public health investments to eliminate systemic barriers in minority communities. Advocates emphasize that culturally tailored medical education, equitable access to non-invasive diagnostic technologies, and inclusive clinical trial representation are essential to ensure that newly developed pharmacological treatments benefit all demographic groups equally.

What we don't know yet

Despite significant advances in clinical research, important uncertainties persist regarding MASLD epidemiology and management. The long-term real-world efficacy, durability, and safety of newly approved MASH medications, including resmetirom, across broader populations outside controlled clinical trials remain to be fully evaluated over multi-year periods.

Additionally, the exact biological mechanisms through which various genetic polymorphisms—such as variants in PNPLA3, TM6SF2, and MBOAT7—interact with dietary, environmental, and socio-economic determinants of health remain incomplete. It is also unclear how effective current non-invasive diagnostic algorithms are at detecting early-stage liver disease across diverse racial groups, particularly in populations where liver fat accumulation does not follow standard clinical patterns. Furthermore, the extent to which public and private insurance providers will cover long-term treatment with novel MASH therapeutics and high-cost metabolic medications for non-diabetic MASLD patients remains a key open question.

What to watch

Moving forward, several key milestones will shape the management of MASLD and its associated comorbidities. Researchers and clinicians are closely tracking data from ongoing late-stage clinical trials evaluating next-generation metabolic compounds, including dual and triple incretin receptor agonists like tirzepatide and retatrutide, to determine their capacity to achieve MASH resolution and reverse established liver fibrosis.

Observers will also monitor the adoption and publication of updated clinical practice guidelines by global medical associations, aimed at institutionalizing routine MASLD screening protocols in primary care clinics and diabetic management programs worldwide. Internationally, healthcare registries and epidemiological tracking systems will monitor long-term shifts in end-stage liver disease incidence, liver transplant waitlist demographics, and cardiovascular event rates to evaluate whether earlier diagnostic detection and novel targeted therapies successfully alter the global trajectory of steatotic liver disease.

This report is based on reporting published by Healthgrades, which outlined the epidemiology, comorbid risks, and healthcare considerations associated with metabolic dysfunction-associated steatotic liver disease across diverse populations.