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. 2025 Jan 2;8(1):e2454707.
doi: 10.1001/jamanetworkopen.2024.54707.

Estimated Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease in US Adults, 2020 to 2050

Phuc Le  1 , Moosa Tatar  1   2 , Srinivasan Dasarathy  3   4 , Naim Alkhouri  5 , William H Herman  6   7 , Glen B Taksler  1 , Abhishek Deshpande  1 , Wen Ye  6 , Olajide A Adekunle  1 , Arthur McCullough  4 , Michael B Rothberg  1
Affiliations

Estimated Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease in US Adults, 2020 to 2050

Phuc Le et al. JAMA Netw Open. .

Abstract

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease and is projected to become the leading indication for liver transplant (LT) in the US. Understanding its clinical burden can help to identify opportunities for prevention and treatment.

Objective: To project the burden of MASLD in US adults from 2020 to 2050.

Design, setting, and participants: This decision analytical modeling study used an agent-based state transition model that simulates the natural history of MASLD progression among adults 18 years of age or older. Primary data sources for model inputs were the published literature.

Exposure: Natural history of MASLD.

Main outcomes and measures: Cases of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, hepatocellular carcinoma (HCC), LT, and liver-related death.

Results: The model simulated 2 821 624 individuals (mean age. 35.8 years; 50.9% female). The model predicted a steady increase in the prevalence of MASLD from 33.7% (86.3 million people) in 2020 to 41.4% (121.9 million people) by 2050. Cases of MASH would increase from 14.9 million (5.8% of US adults) in 2020 to 23.2 million (7.9% of US adults) by 2050. The number of cases of MASH and clinically significant fibrosis (ie, F≥F2, centrilobular and periportal fibrosis or more severe disease) were estimated to increase from 6.7 million to 11.7 million. By 2046 to 2050, MASLD would cause 22 440 new cases of HCC and 6720 new cases of LT per year compared with 11 483 new cases of HCC and 1717 new cases of LT in 2020 to 2025. Liver-related mortality was estimated to increase from 30 500 deaths (1.0% of all-cause deaths in adults) in 2020 to 95 300 deaths (2.4%) in 2050.

Conclusions and relevance: In this decision analytical modeling study, the model forecast a substantial increase in clinical burden of MASLD over the next 3 decades in the absence of effective treatments. These results suggest that health systems should plan for large increases in the number of HCC cases and in the need for LT.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dasarathy reported receiving grants from Cleveland Clinic during the conduct of the study. Dr Alkhouri reported receiving grants from 89bio, Akero Therapeutics, Arbutus Biopharma, AstraZeneca, Better Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Corcept Therapeutics, CymaBay Therapeutics, DSM, Galectin Therapeutics, Genentech, Genfit, Gilead Sciences, Healio, Hepagene Therapeutics, Intercept Pharmaceuticals, Inventiva Pharma, Ionis Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Noom, NorthSea Therapeutics, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking Therapeutics, and Zydus Pharmaceuticals during the conduct of the study; personal fees from 89bio, Boehringer Ingelheim, Echosens, Fibronostics, Gilead Sciences, Intercept Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk, and Perspectum Consulting outside the submitted work. Dr Herman reported receiving grants from the Agency for Healthcare Research and Quality (AHRQ) during the conduct of the study. Dr Taksler reported receiving grants from National Institute on Aging during the conduct of the study. Dr Deshpande reported receiving personal fees from Merck outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Model Diagram of the Progression of Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD)
In each cycle, people can die from other causes of death from any of these health states. F0 to F4 represent fibrosis stage 0 (no fibrosis) to 4 (cirrhosis); HCC, hepatocellular carcinoma; MASH, metabolic dysfunction–associated steatohepatitis, MASL, metabolic dysfunction–associated steatotic liver.
Figure 2.
Figure 2.. Model Prediction of Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) Burden From 2020 to 2050, by MASLD and Metabolic Dysfunction–Associated Steatohepatitis (MASH) Status and by Age Group
Figure 3.
Figure 3.. Model Prediction of Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) Burden From 2020 to 2050 by Fibrosis Stage for All MASLD and Metabolic Dysfunction–Associated Steatohepatitis (MASH) Cases
F0 to F4 represents fibrosis stage 0 (no fibrosis) to 4 (cirrhosis).
Figure 4.
Figure 4.. Model Prediction of Annual Incident Metabolic Dysfunction–Associated Steatotic Liver Disease–Related Hepatocellular Carcinoma and Liver Transplant Between 2020 and 2050
See this image and copyright information in PMC

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