MASH: Liver health’s silent epidemic
Liver disease is a growing global health concern, yet many of its most serious forms remain under-recognised and underdiagnosed. Metabolic dysfunction-associated steatohepatitis (MASH) stands out as a particularly urgent challenge. MASH is a progressive liver condition closely tied to metabolic dysfunction. It has been estimated that MASH cases in the United States will increase by 82.6% to19.53 million by 2039.1 MASH is also quickly becoming one of the leading causes of liver-related morbidity and mortality in the United States with a recent study indicating MASH as the second leading cause and the most rapidly increasing indication of liver transplantation in patients without hepatocellular cancer.2
Despite its prevalence, MASH often goes unnoticed until advanced stages, earning its reputation as a silent disease. With rising rates of obesity, type 2 diabetes and other cardiometabolic conditions, the burden of MASH is expected to grow significantly in the coming years. Fortunately, recent advances in diagnostics, a change of nomenclature and new treatments offer new hope for earlier detection and more effective management.
This blog explores the evolving understanding of MASH, its clinical and demographic impact and the real-world data shaping how we respond to this hidden epidemic.
A new name for greater clarity
Previously, MASH was known as nonalcoholic steatohepatitis (NASH), part of the broader category of nonalcoholic fatty liver disease (NAFLD). These terms were increasingly seen as problematic: defining the disease by what it is not (alcohol-related) and using stigmatising language such as “fatty”.
In 2023, liver experts globally adopted a new nomenclature. NAFLD became metabolic dysfunction-associated steatotic liver disease (MASLD) and NASH was renamed MASH, reflecting its direct link to metabolic dysfunction.3,4
This shift aims to:
- Improve patient understanding
- Reduce stigma
- Clarify diagnostic pathways
The change in name better captures the complex, systemic nature of the disease, laying the groundwork for more precise research and clinical care.
The scale of the crisis
MASH is rapidly emerging as one of the most urgent challenges in liver health. It is now the leading cause of chronic liver disease, with a growing clinical burden and projections suggesting it will soon become the primary driver of liver cancer and transplants in the United States.2,5 Despite this alarming trajectory, the majority of patients remain undiagnosed.6,7
Who is affected?
Real world data from Symphony Health, an ICON plc company, provides insight into the demographic profile of MASH patients. Analysing patients in the US with at least one medical claim for MASH between January 2020 and December 2024, the data show:
- Median age: 59 years
- Gender: Slight female predominance (58%)
- Ethnicity: Majority Caucasian (71%)
Source: Symphony Health, an ICON plc company: Open claims data from Integrated Dataverse (IDV®) - Patients with at least 1 MASH diagnosis claim from January 2020-December 2024. For cirrhosis, they also need at least 1 diagnosis claim indicating cirrhosis. For no cirrhosis, they did not have any diagnosis claims indicated cirrhosis within the timeframe.
Given the nature of this silent disease, Real world data can help identify the characteristics of patients and those factors that may help physicians and other care practitioners better identify patients who are likely to have MASH. This promotes more testing, earlier diagnosis and earlier treatment.
Why so many go undiagnosed
One of the greatest challenges with MASH is its asymptomatic nature in early stages. Patients often show no signs until significant liver damage or cirrhosis has occurred. Routine liver function tests are frequently inadequate. The current gold standard, liver biopsy, is invasive, expensive and impractical for widespread screening.6
These factors, combined with low awareness among both patients and clinicians, has led to widespread underdiagnosis. For millions of patients worldwide, progressive liver disease remains hidden until it is too late for effective intervention. However, recent advances in non-invasive diagnostics, such as composite scores with laboratory tests (e.g., FibroScan-AST [FAST] score, MRI-AST [MAST] score) and treatment options offer hope.
A turning point in treatment
For decades, there were no approved treatments for MASH. That changed in March 2024, when the US Food and Drug Administration (FDA) approved resmetirom (Rezdiffra™) — the first treatment for adults with non-cirrhotic MASH and moderate to advanced fibrosis.8
Resmetirom is a thyroid hormone receptor-β agonist that mimics localised hyperthyroidism, reducing lipid accumulation and liver fibrosis. In the pivotal MAESTRO-NASH trial, it demonstrated both histological resolution of MASH and improvement in fibrosis.9
In August 2025, the FDA approved semaglutide (Wegovy®) for adults with MASH and moderate to advanced fibrosis.10 Already approved for type 2 diabetes, obesity and cardiovascular risk reduction, semaglutide (a GLP-1 agonist) showed promising results in the ESSENCE trial, including histological resolution and fibrosis improvement.11
These approvals mark a new era in MASH management. While lifestyle changes remain essential, clinicians now have pharmacological tools to slow disease progression. The treatment pipeline is expanding rapidly, with several promising therapies under investigation.12
The burden of comorbidities
MASH rarely exists in isolation and is often deeply intertwined with other chronic conditions such as obesity and type 2 diabetes.13,14 Most patients live with multiple cardiometabolic comorbidities which accelerate liver disease progression and complicate treatment.
Among those with cirrhosis, the prevalence of comorbidities is even higher, highlighting the strong link between advanced liver disease and systemic metabolic dysfunction.
Effective management requires more than just targeting MASH. A holistic approach that addresses weight, glycaemic control, blood pressure and lipid levels is essential for optimal care.
Looking ahead
MASH is a silent epidemic with global implications. Left unaddressed, it will continue to drive rising rates of cirrhosis, liver transplantation and healthcare costs.
Fortunately, the landscape is changing and entering a transformative phase. This is due to:
- New nomenclature improving clarity
- Non-invasive tools enabling earlier detection
- The first wave of approved therapies entering practice
Real world data plays a key role in bridging research and practice with supporting clinical trial design through patient identification, site selection, and external control arms, while informing commercialization by mapping patient journeys, treatment patterns, and payer dynamics. Real-world data also plays a crucial role in understanding how MASH is diagnosed, treated and managed outside clinical trials. These insights help identify undiagnosed patients, close gaps in care and measure the impact of new therapies.
The challenge is clear. Dealing with MASH requires increasing awareness, reducing stigma, expanding screening and ensuring equitable access to innovative treatments. By combining clinical progress with real world evidence and a comprehensive patient journey, we can bring MASH out of the shadows to change the future of liver health.
Connect with us to discover how integrated healthcare data can support your clinical research.
References
1 Younossi ZM, Paik JM, Henry L, et al. The Growing Economic and Clinical Burden of Nonalcoholic Steatohepatitis (NASH) in the United States. J Clin Exp Hepatol. 2023;13(3):454-467. doi:10.1016/j.jceh.2022.12.005
2 Younossi ZM, Stepanova M, Ong J, et al. Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States. Clin Gastroenterol Hepatol. 2021;19(3):580-589.e5. doi:10.1016/j.cgh.2020.05.064Rinella ME, Sookoian S. From NAFLD to MASLD: updated naming and diagnosis criteria for fatty liver disease. J Lipid Res. 2024;65(1):100485. doi:10.1016/j.jlr.2023.100485
3 Rinella ME, Sookoian S. From NAFLD to MASLD: updated naming and diagnosis criteria for fatty liver disease. J Lipid Res. 2024;65(1):100485. doi:10.1016/j.jlr.2023.100485
4 Yilmaz Y. The heated debate over NAFLD renaming: An ongoing saga. Hepatol Forum. 2023;4(3):89-91. Published 2023 Sep 7. doi:10.14744/hf.2023.2023.0044
5 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. Published 2025 Jan 2. doi:10.1001/jamanetworkopen.2024.54707
6 Lazarus JV, Brennan PN, Mark HE, et al. A Call for Doubling the Diagnostic Rate of At-Risk Metabolic Dysfunction-Associated Steatohepatitis. Lancet Reg Health Eur. 2025;54:101320.
7 Alexander M, Loomis AK, Fairburn-Beech J, et al. Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease. BMC Med. 2018;16(1):130. Published 2018 Aug 13. doi:10.1186/s12916-018-1103-x
8 FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. FDA News Release. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease. Published Mar 14 2024. Accessed Sep 29 2025.
9 Mousa AM, Mahmoud M, AlShuraiaan GM. Resmetirom: The First Disease-Specific Treatment for MASH. Int J Endocrinol. 2025;2025:6430023. Published 2025 Feb 26. doi:10.1155/ije/6430023
10 FDA Approves Treatment for Serious Liver Disease Known as ‘MASH’. FDA News Release. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash. Published Aug 15 2025. Accessed Sep 29 2025.
11 Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089-2099. doi:10.1056/NEJMoa2413258
12 Noureddin M. MASH clinical trials and drugs pipeline: An impending tsunami. Hepatology. Published online March 19, 2024. doi:10.1097/HEP.0000000000000860
13 Sandireddy R, Sakthivel S, Gupta P, Behari J, Tripathi M, Singh BK. Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases. Front Cell Dev Biol. 2024;12:1433857. Published 2024 Jul 16. doi:10.3389/fcell.2024.1433857
14 Younossi ZM, Mangla KK, Chandramouli AS, Lazarus JV. Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH. Hepatol Commun. 2024;8(8):e0488. Published 2024 Jul 22. doi:10.1097/HC9.0000000000000488