Global MASH Burden Projected to Double Costs, Raise Mortality Without Intervention

Metabolic dysfunction–associated steatohepatitis (MASH) is on track to drive major clinical and economic consequences worldwide, according to new projections that estimate costs could more than double by 2040 if no action is taken.¹

Using a Markov model calibrated with national data, researchers modeled disease progression across 9 countries between 2021 and 2040: the US, Germany, Spain, France, Italy, the UK, Japan, Brazil, and Saudi Arabia. The analysis integrated the prevalence of obesity and type 2 diabetes, transition probabilities for liver disease progression, and country-specific costs to capture the comprehensive impact of MASH. Findings were published in Clinical Gastroenterology and Hepatology.

Rising Prevalence and Advanced Disease

Prevalence is expected to climb steadily across the 9 countries, with the highest estimates in Brazil and the lowest in France:

Direct medical costs are forecast to more than double by 2040. | Image credit: Philip Steury – stock.adobe.com

• Brazil, from 7.19% to 7.52%
• Saudi Arabia, from 7.39% to 7.50%
• US, from 6.7% to 7.4%
• Spain, from 4.5% to 5.4%
• Italy, from 4.58% to 5.37%
• UK, from 4.75% to 5.21%
• Japan, from 3.7% to 5.0%
• Germany, from 4.43% to 4.97%
• France, from 4.04% to 4.50%

Importantly, advanced MASH—including stage F3 fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and liver transplant—is projected to rise by at least 20% in every country. In the US alone, there are about 4.3 million cases of MASH with advanced fibrosis as of 2025, and this number could reach nearly 5 million by 2040, with about 200,000 new cases every 5 years. Meanwhile, cases of MASH with DCC are expected to grow from 590,880 to 704,753, cases with HCC from 10,522 to 15,057, and cases with liver transplant from 1952 to 2398.

US Maintains Highest Mortality Rate

Mortality rates are also projected to grow over the next 15 years, with the highest overall rate in the US both in 2025 (247.21 per 100,000) and 2040 (261.08 per 100,000). Italy, Spain, Germany, and France followed in 2040 estimated prevalence, with rates of 213.85, 196.43, 180.75, and 153.84 per 100,000, respectively. Rates are expected to still rise but be much lower in Saudi Arabia (0.88 per 100,000), Brazil (0.38 per 100,000), the UK (0.28 per 100,000), and Japan (0.07 per 100,000).

Rates of cardiovascular disease (CVD)–related and liver-related MASH deaths also increased across the board. Saudi Arabia saw the largest increase in CVD-related death rates between 2025 and 2040, climbing from 137.63 deaths to 206.66 per 100,000. Brazil followed, climbing from 213.24 to 262.59 per 100,000. The rate in the US is currently 52.58 per 100,000 and is projected to rise to 55.12 per 100,000, while the UK and Japan are projected to reach much higher rates at 176.69 and 168.7 deaths per 100,000, respectively. The lowest 2040 rate was estimated in France at 26.48 deaths per 100,000.

Liver-related MASH deaths are much less common, but Saudi Arabia again saw the largest increase in mortality rates, with estimates climbing from 34.31 to 51.93 deaths per 100,000; Brazil again followed, going from 47.58 to 58.63 per 100,000. The US is currently estimated to have 11.62 deaths per 100,000, increasing to 12.42 per 100,000. Liver-related deaths are again estimated to be higher in the UK (31.58 per 100,000) and Japan (31.51 per 100,000) in 2040 than in the US, while France has the lowest rate (10.25 per 100,000).

Economic Toll of MASH

Direct medical costs are forecast to more than double, reaching $78.6 billion annually in the US in 2040—more than 6 times the total of the other 8 countries combined. As a result, per-patient costs are estimated to rise from $2291 to $3601. MASH-associated productivity loss is also estimated to rise from $128.6 billion to $246 billion, costing $11,300 per patient in 15 years compared with the current $7126.

“Without intervention, the clinical, economic, and quality-of-life burden of MASH is projected to increase across most regions of the world,” the authors concluded. “These findings highlight the urgent need for both national and global strategies to reduce the negative impact of MASH on individuals and society.”

These projections align with recent evidence showing how the burden of MASH translated into downstream complications. Global Burden of Disease 2021 data found that MASH-related liver cancer among adults aged 65 and older more than doubled in incidence, deaths, and disability-adjusted life years between 1990 and 2021.² According to the data, men carry a higher disease burden than women, with low- and middle-income regions disproportionately affected. East Asia, South Asia, and high-income North America had the most cases of MASH-related liver cancer in 2021, while the lowest numbers were recorded in Oceania, central Sub-Saharan Africa, and the Caribbean.

Reference

1. Younossi ZM, Paik JM, Lazarus JV, et al. Supplementary material for projected global clinical, humanistic, and economic impact of metabolic dysfunction-associated steatohepatitis (MASH): the cost of inaction based on data from nine countries. Clin Gastroenterol Hepatol. Published online September 8, 2025. doi:10.1016/j.cgh.2025.09.002
2. Klein HE. Global burden of MASH-related liver cancer rising sharply among older adults. AJMC^®. August 26, 2025. Accessed September 11, 2025. https://www.ajmc.com/view/global-burden-of-mash-related-liver-cancer-rising-sharply-among-older-adults