Globally, the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) which is also known as non-alcoholic fatty liver disease (NAFLD) has shifted dramatically, reaching 38% of adults in North America and Australia by 2019. MASLD along with its more severe form, metabolic dysfunction–associated steatohepatitis (MASH), poses significant risks for adverse liver outcomes, including liver transplantation. According to estimates most of the liver transplants performed in the US are caused by MASH.
In 2023, the term MASLD was redefined to emphasize its association with metabolic dysfunction despite all NAFLD patients being categorized under MASLD. Pioglitazone and glucagon-like peptide-1 receptor agonists currently being used for obesity have the potential to enhance MASH and its related fibrosis. As there are higher incidences of MASLD and MASH cases it is important for the healthcare facilities and the pharmaceutical industries to identify the clinical implications and predict the probable growth of the disease to handle the emergent need for medicines and proper care.
The analytical modeling study is conducted based on approval from the Cleveland Clinic Institutional Review Board and adheres to the strengthening of the reporting of empirical simulation studies (STRESS) checklist. A state transition model with yearly cycle and horizons by lifetime was established based on agent-based micro-simulation to reflect variability and heterogeneity of the population. The features include demographics and interventional-based annual incidence and prevalence mimicking a hypothetical US population that began with 2,821,624 subjects in 2000 followed up to assess the natural history of MASLD in the adult population. The model assumed a hypothetical US population that grew by births and decreased by mortality and migration while the people moved through the different health states of steatosis, MASH, fibrosis, cirrhosis, hepatocellular carcinoma (HCC), liver transplant (LT), and liver-related death.
US-based studies informed the incidence and prevalence data, with careful calibration of unknown parameters to enhance model accuracy. The transition probabilities from one health state to another were derived from meta-analyses and longitudinal studies on the conversion of patients from steatosis to MASH and between fibrosis stages. The accuracy of models was confirmed based on a comparison between predicted demographics and the actual US population as well as based on the National Health and Nutrition Examination Survey (NHANES), surveillance, epidemiology, and end results (SEER), and United Network for Organ Sharing (UNOS) datasets.
The study estimated that 33.7% of U.S. adults had MASLD in 2020 with a projection of increase in the future to 41.4% by 2050 with 121.9 million people at risk. The prevalence of this disease in the elderly would seem to rise greatly, especially those above 80 years old is expected to rise dramatically with a 300% increase. Fibrosis stages would also increase by 2050 41.6% of patients at the F0 stage and 4.0% at the F4 stage.
This model predicted an extensive increase in the incidence of HCC, from 11483 in the calendar year 2020 to 22440 in 2050 as well as an increase in LT and liver-related mortality. The MASLD-related mortality by the year 2050 will be 95,300 mortalities per year. The study was able to find out that if the occurrence of MASLD does not decrease then the persistence rate will increase to 38.2% by 2050. However, if it rises further then it will reach 42.9%.
By 2050, MASLD is projected to affect 41.4% of the adult population in the US, with complications including fibrosis, cirrhosis and the eventual need for a liver transplant will rise exponentially. This model presents a more accurate estimate than previous studies because it uses current data considering the new rates of obesity and diabetes. However, barriers like high costs associated with the drug, sky-high pricing pressures, accessibility, and the requisite for improved monitoring are still present. The observational data used might be inaccurate, incomplete, and biased and thus insert uncertainty in the evaluation results. Therefore, there is a need for further research on efficient and economic approaches to cases of this rising health concern.
The prevalence of MASLD in the US is likely to rise in the next 30 years underscores the urgent need for increased investment in research, preventive measures, and enhanced health system preparedness.
References: Le P, Tatar M, Dasarathy S, et al. Estimated burden of metabolic dysfunction–associated steatotic liver disease in US adults, 2020 to 2050. JAMA Netw Open. 2025;8(1): e2454707. doi:10.1001/jamanetworkopen.2024.54707
