Roughly 8 Million US Adults May be Eligible for Resmetirom Treatment for MASH

A substantial number of US adults fall within the eligibility criteria for resmetirom for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced liver fibrosis (stages F2-F3), according to a recent study.1

Metabolic dysfunction-associated steatotic liver disease (MASLD), of which MASH is a possible outcome, is the most prevalent chronic liver disease in the world. It affects roughly 38% of the adult population and almost 10% of children globally.2,3

Additionally, MASLD is more prevalent in patients with type 2 diabetes mellitus (T2DM), and patients with both conditions often exhibit histologically confirmed MASH and advanced fibrosis. This connection has risen in recent years from 55% to 65%, which has given rise to concern over the hepatologic implications, particularly because 66% of patients with T2DM and MASLD often exhibit histologically confirmed MASH, and 15% present with advanced fibrosis.1

Resmetirom, an oral thyroid hormone receptor beta-selective agonist, is the first liver-targeted medication approved by the US Food and Drug Administration (FDA), specifically indicated for patients with noncirrhotic MASH and fibrosis stages F2-F3. The MAESTRO-NASH trial proved resmetirom’s safety and efficacy in promoting histological improvement in MASLD; however, despite its efficacy, the exact size of the eligible patient population is unknown.1

“To address these knowledge gaps, we sought to estimate the eligible population based on NITs from the MAESTRO-NASH trial, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017—March 2020 cycle, which provides a representative sample of the US population,” wrote Phuc Le, PhD, MPH, assistant professor of medicine at Cleveland Clinic Lerner College of Medicine, and colleagues.1

Investigators selected adult participants ≥18 years for analysis; patients with documented liver cirrhosis, pregnant women, individuals with viral hepatitis, and those reporting excess alcohol consumption were excluded.1

An initial total of 15,560 patients were selected; 6537 were excluded due to incomplete examinations, 709 due to missing ALT data, and 1075 for meeting ≥1 of the exclusion criteria. The final analysis included 7244 adults with a mean age of 49 years. T2DM prevalence was 18.6% (n = 1349), and obesity was 43.2% (n = 3103). Mean ALT and AST levels were 22.4 and 21.9 U/L, respectively. FibroScan examinations indicated a mean CAP of 263 dB/m and LSM of 5.8 kPa.1

Investigators established 2 sets of criteria, liberal and stringent. When applying the liberal criteria, 2801 participants (38.67%) exhibited a CAP value >280 dB/m, 704 (9.72%) had an LSM >8 kPa, and 3158 (43.57%) had elevated ALT levels, defined as >17 U/L for women and >20 U/L for men. A total of 276 (3.81%) met all 3 criteria, corresponding to roughly 8.3 million individuals in the US population (4%; 95% CI, 3.2-4.8%).1

The stringent criteria application saw 75 individuals fulfill the requirements, representing an estimated 2.3 million individuals (1.1%; 95% CI, .7%-1.5%). This group was predominantly male (76.2% versus 59.9%), younger (46.7 versus 48.3 years), and exhibited similar body mass index (36.6 versus 38.1 kg/m2). The stringent criteria group also had higher transamine levels. Despite having the same CAP threshold, the mean CAP value was higher in patients meeting the stringent criteria.1

T2DM was identified in 1349 participants (18.62%), of which 140 patients (10.38%) met the liberal criteria for resmetirom and 39 (2.89%) met the stringent criteria. These percentages correspond with roughly 3.5 million and 800,000 individuals, respectively.1

The team noted these percentages as indicating approximately 8.4 million individuals in the US are eligible for resmetirom therapy.1

“This significant treatment-eligible population underscores the need for rigorous patient selection protocols to optimize cost-effectiveness, integration of resmetirom into comprehensive healthcare struggles, and standardization of diagnostic approaches,” Le and colleagues wrote. “These insights provide valuable guidance for healthcare stakeholders in resource allocation and therapeutic implementation strategies, particularly as we advance toward more precise and cost-effective treatment paradigms in MASH management.”1

References

1. Le P, Kaya E, Phan A, Yilmaz Y, Alkhouri N. Resmetirom-eligible population among US adults: An estimation analysis based on NHANES 2017–March 2020. Hepatology Communications. 2025;9(7). doi:10.1097/hc9.0000000000000755

2. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review. Hepatology. 2023;77(4):1335-1347. doi:10.1097/hep.0000000000000004

3. Paik JM, Kabbara K, Eberly KE, Younossi Y, Henry L, Younossi ZM. Global burden of NAFLD and chronic liver disease among adolescents and young adults. Hepatology. 2021;75(5):1204-1217. doi:10.1002/hep.32228