New Study Shows Resmetirom Improves QOL for Patients Across the MASLD Spectrum

Patients living with metabolic dysfunction–associated steatotic liver disease (MASLD) often face a significant burden that extends beyond liver damage, affecting their daily functioning, emotional well-being, and overall quality of life. New research suggests that treatment with thyroid hormone receptor-β agonist resmetirom may help address not only the biological drivers of disease but also the patient-reported symptoms that impact everyday life.

The findings come from an analysis of the phase 3 MAESTRO-NAFLD-1 clinical trial program, which evaluated health-related quality of life (HRQOL) outcomes in patients with metabolic dysfunction–associated steatohepatitis (MASH), a progressive form of MASLD that can lead to fibrosis, cirrhosis, and liver failure. Researchers recently published these findings in Hepatology Communications.

As the treatment landscape for MASLD and MASH continues to evolve, the incorporation of HRQOL measures into clinical trials may help ensure that emerging therapies deliver benefits that matter most to patients, noted the researchers of their findings, adding that these new findings support the growing role of resmetirom as a therapy capable of addressing both the biological and humanistic burden of disease.

Approved by the FDA as Rezdiffra (Madrigal Pharmaceuticals) in 2024,² the drug selectively activates thyroid hormone receptor-β in the liver, helping reduce hepatic fat accumulation, inflammation, and fibrosis while avoiding the systemic side effects associated with thyroid hormone therapy.

To understand how treatment affects patients beyond traditional clinical endpoints, investigators analyzed HRQOL data from more than 1300 individuals enrolled in the MAESTRO-NAFLD-1 trial who were followed for up to 2 years. The study included 1,143 patients with early MASH and 180 with well-compensated MASH cirrhosis.

The team used 2 validated instruments—the Chronic Liver Disease Questionnaire for NAFLD (CLDQ-NAFLD) and the Liver Disease Quality of Life (LDQOL) survey—to assess patient-reported outcomes. These tools evaluate multiple domains, including abdominal symptoms, fatigue, emotional health, social functioning, and disease-related worry.

At baseline, patients with cirrhosis reported substantially worse quality-of-life scores than those with earlier disease, highlighting how symptom burden increases as liver damage progresses. Over the course of treatment, patients receiving resmetirom experienced improvements in several key HRQOL domains compared with placebo. Among individuals with early MASH, notable gains were observed in measures of abdominal symptoms, worry about disease, and health distress. Improvements became evident by week 24 and were sustained through week 52.

Importantly, these benefits were most pronounced among patients who achieved significant reductions in liver fat, measured using magnetic resonance imaging–proton density fat fraction (MRI-PDFF). Patients who experienced at least a 30% reduction in hepatic fat showed greater improvements in symptom-related quality-of-life scores than nonresponders or those receiving a placebo. Improvements in stomach symptoms, worry, and total CLDQ-NAFLD scores were statistically significant (P < .05).

These findings, wrote the researchers, suggest that improvements in underlying liver pathology may translate into tangible gains in how patients feel and function in their daily lives.

The study also demonstrated improvements among patients with well-compensated MASH cirrhosis, a group with limited treatment options. Participants receiving resmetirom reported sustained improvements in emotional well-being, particularly in domains related to disease-related worry and health distress.

“Interestingly, some HRQOL domain scores related to sleep, concentration/memory, and symptoms of liver disease showed declines (worsening) over time,” noted the researchers. “In patients with cirrhosis, the decline in cognitive function may reflect neuropsychiatric status with disease progression, and general worsening of symptoms may also reflect the natural history of this advanced disease.”

Among those who responded to treatment with reductions in liver fat, additional benefits included improvements in perceived stigma associated with liver disease and stabilization of social and emotional measures that otherwise worsened in nonresponders.

References:

1. Younossi ZM, Nader F, Labriola D, et al. Improvement in health-related quality of life after treatment with resmetirom in patients with the spectrum of MASLD: From early MASH to MASH cirrhosis. Hepatol Commun. 2026;10(3):e00913. doi:10.1097/HC9.0000000000000913
2. FDA approves first treatment for patients with liver scarring due to fatty liver disease. FDA news released. Published online March 14, 2024. Accessed March 11, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease