MASLD Prevalence Projected to Exceed 40% by 2050, Increasing Health System Burden

Phuc Le, PhD, MPH

Credit: Cleveland Clinic

New research is shedding light on the projected clinical burden of metabolic dysfunction-associated steatotic liver disease (MASLD) in the absence of effective treatments over the next 3 decades.¹

The decision analytical modeling study estimated the prevalence of MASLD would reach 41.4%, equating to approximately 122 million US, in 2050, additionally calling attention to stark increases in prevalent cases of decompensated cirrhosis, incident cases of liver cancer, and the need for liver transplantation.¹

“Understanding the clinical burden of MASLD, especially the number of patients eligible for pharmacologic treatment, could enable health systems and pharmaceutical companies to prepare to meet imminent demand, but estimates vary widely, posing planning challenges,” Phuc Le, PhD, MPH, associate staff at Cleveland Clinic Community Care and an assistant professor of medicine at Cleveland Clinic Lerner College of Medicine, and colleagues wrote.¹

On March 14, 2024, resmetirom (Rezdiffra) became the first-ever liver-directed MASH therapeutic to earn US Food and Drug Administration (FDA) approval for the treatment of the progressive liver disease.² It remains the only FDA-approved pharmacologic option, although other molecules are progressing through clinical development. Understanding the clinical burden of MASLD, including the number of patients eligible for pharmacologic treatment, is essential for preparing health systems and pharmaceutical companies.

To project the burden of MASLD in US adults from 2020 to 2050, investigators conducted a decision analytical modeling study using an agent-based state transition model with a yearly cycle and lifetime time horizon to simulate the natural history of MASLD progression.¹

The first component of the model represents a hypothetical population with age and sex distribution reflecting the US population in 2000 simulated until 2050. At the model start, investigators simulated 2,821,624 individuals and incorporated births and immigrants every year based on US Census Bureau data and mortality based on life tables.¹

The second component of the model tracks the natural history of MASLD in individuals ≥ 18 years of age, modeling the following health states: no steatosis; simple steatosis or metabolic dysfunction–associated steatotic liver (MASL); MASH; fibrosis with or without MASH; cirrhosis; decompensated cirrhosis; hepatocellular carcinoma; liver transplant (LT); and liver-related death. At the end of each cycle, an individual may remain in the same state or move to a more or less severe state with predefined probabilities.¹

For each input of the natural history model component, investigators conducted a literature review of US-based studies to reflect MASLD epidemiology in the adult population. For unknown parameters, they used calibration to estimate values.¹

The cohort simulated in the model had a mean age of 35.8 years and was predominantly (50.9%) female. Calibration and validation measures showed the model accurately replicated the growth of the US population from 2000 to 2020 and came close to other previously published estimates predicting the overall prevalence of MASLD among US adults from 2001-2018, the age-specific prevalence in 2018, the proportion with MASH, the number of HCC cases, and survival.¹

Results showed the model predicted steady growth in the prevalence of MASLD, increasing from 33.7% (86.3 million people) in 2020 to 41.4% (121.9 million people) by 2050. Additionally, the model predicted cases of MASH would increase from 5.8% (14.9 million people) in 2020 to 7.9% (23.2 million people) by 2050.¹

Stratifying by fibrosis stage, 48.4% of patients with MASLD did not have fibrosis in 2020, while 29.1% had F1; 14.5% had F2; 5.7% had F3; and 2.2% had F4. By 2050, disease was projected to be more advanced, with larger proportions of individuals having F2 (17.4%), F3 (8.4%), and F4 (4.0%).¹

The population with MASH and ≥ F2 fibrosis increased by 75%, from 6.7 million in 2020 to 11.7 million in 2050. Investigators noted the prevalence increased across fibrosis stages, with higher rates observed among more advanced stages.¹

The model predicted a mean 11,483 new cases of HCC and 1717 LTs per year from 2020 through 2025. This figure increased to 22,440 new cases of HCC and 6720 LTs per year from 2046 through 2050 for a cumulative total of 527,900 new MASLD-related HCC cases and 132,600 LTs. Additionally, liver-related mortality was estimated to increase from 30,500 incident deaths (1.0% of all-cause deaths in adults) in 2020 to 95,300 deaths (2.4%) in 2050.¹

“This decision analytical modeling study estimates a substantial burden of MASLD in the next 30 years in the US,” investigators concluded.¹ “By implementing preventive strategies, investing in research, and preparing health care systems, we can minimize the impact of MASLD and improve the lives of millions of individuals affected by this disease.”

References

1. ^{Le P, Tatar M, Dasarathy S, et al. Estimated Burden of Metabolic Dysfunction–Associated Steatotic Liver Disease in US Adults, 2020 to 2050. JAMA Network Open. 2025;8(1):e2454707. doi:10.1001/jamanetworkopen.2024.54707}
2. ^{Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed January 16, 2025. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash}