Health-Related Quality of Life Improvements With Resmetirom, With Zobair Younossi, MD, MPH

While the hepatic benefits of resmetirom (Rezdiffra) are well established following its US Food and Drug Administration approval for metabolic dysfunction-associated steatohepatitis (MASH), new research is shedding light on the treatment’s impact on health-related quality of life (HRQoL).

The data were presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025 by Zobair Younossi, MD, MPH, chairman of the Global NASH/MASH Council and professor and chairman of Beatty Liver and Obesity Research at Inova Health System, and highlight improvements in select disease-specific HRQoL scores among patients without or with cirrhosis due to MASLD treated with resmetirom in the phase 3 MAESTRO-NAFLD trial.

“As physicians, we always look at biochemical, physiological, liver histology or NITs as ‘important’ endpoints or outcomes, but from a patient's perspective, it's how they feel, how they experience the disease or the treatment,” Younossi explained to HCPLive. “To me, that should be the most important, because if you're going to do patient-centered care, then the patient has to be at the center…. In my opinion, putting the patient-reported outcome at least on an equal footing to the physiological, biochemical and other outcomes is extremely important.”

Research he presented at AASLD explored the HRQoL impacts of treatment with resmetirom in MAESTRO-NAFLD. Patients with MASLD with cirrhosis (CP-A) or MASLD without cirrhosis were enrolled in a 52-week, phase 3 double-blind placebo-controlled study of resmetirom (Period 1 of MAESTRO-NAFLD) and upon treatment completion, were offered to enroll in a 52-week open-label extension study of resmetirom (Period 2). HRQoL was assessed using LDQOL, CLDQ-NAFLD and WPAI throughout treatment period 1 at baseline, week 24, week 52 and treatment Period 2 at day 1, week 12, week 28, and week 52.

For non-cirrhotic MASLD, PDFF response was defined as a decrease in MRI-PDFF ≥30% from baseline. For cirrhotic MASLD, it was defined as ≥20% decrease in MRI-PDFF if baseline MRI-PDFF was >5%.

MAESTRO NAFLD included a total of 1307 MASLD patients. Of these, 193 had cirrhosis (23% with baseline MRI-PDFF ≤5%) and 1114 were without cirrhosis (baseline MRI-PDFF ≥8%).

At baseline, HRQoL scores of patients with cirrhosis were significantly lower (up to -16% of score range) for all 6 domains of CLDQNAFLD, 14/17 domains of LDQOL, Activity Impairment of WPAI (p<0.05). Among patients with cirrhosis, there was no significant difference in baseline HRQL scores between those with MRI-PDFF ≤5% and >5% (all P >.05). By week 24 of treatment with resmetirom during period 1, patients with cirrhosis experienced improvements in Worry (CLDQ-NAFLD) and Health Distress (LDQOL) up to +4% of score range which sustained by week 52 and throughout Period 2 (P <.05).

In cirrhotic patients with MRI-PDFF >5%, PDFF response by Period 1 week 52, there was an improvement in Stigma score (LDQOL; mean change, +4.0 vs -5.7; P = .011). By weeks 24 and 52 of treatment, non-cirrhotic patients receiving placebo experienced worsening of HRQL in some physical health-related domains of LDQOL (mean decrease up to -5%; P <.05) while no decreases were observed in non-cirrhotic patients treated with resmetirom.

Additionally, non-cirrhotic patients receiving resmetirom experienced improvement in Abdominal and Worry domains of CLDQ-NAFLD and Health Distress of LDQOL (mean increase up to +5% of score range size), while no similar improvements were observed in placebo (all P >.05). Non-cirrhotic patients with PDFF response also experienced improvements in Abdominal and Worry scores (up to +7%), which were greater than those seen in placebo or non-responders.

“From my perspective, the PROs really have 2 important aspects in this context,” Younossi explained. “One is that the drug that you're using is not worsening patients' quality of life, because some drugs, historically, interferon for hepatitis C, have caused a lot of side effects, and quality of life actually took a dive. Here, not only are you not seeing a decline in quality of life, but you're actually seeing improvement, so you're improving our patient's experience and how they feel.”

Editors' note: Younossi reports relevant disclosures with Intercept, Gilead, Boehringer Ingelheim, Ipsen, Bristol-Myers Squibb, GSK, NovoNordisk, Siemens, Madridgal, Merck, Akero and Abbott.

References

1. Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed November 11, 2025. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash

2. Younossi Z, Nader F, Labriola D, et al. Improvement In Health-Related Quality of Life After Treatment with Resmetirom in Cirrhotic and Non-Cirrhotic Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Data From MAESTRO‑NAFLD. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.