Quality of Life With Resmetirom in MASH Cirrhosis: Zobair Younossi, MD, MPH

Resmetirom (Rezdiffra) was associated with modest improvements in disease-related worry and health distress among patients with compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis, according to a post hoc analysis of the phase 3 MAESTRO-NAFLD-1 trial presented at AASLD The Liver Meeting 2026.¹

Zobair Younossi, MD, MPH, chairman of the Global NASH/MASH Council, presented the findings and discussed them in an interview with HCPLive. He described health-related quality of life (HRQL) as central to the comprehensive burden of MASH, alongside clinical and economic burden, and noted quality of life tends to worsen as liver disease advances.

How Did Resmetirom Affect Quality of Life in MASH Cirrhosis?

The analysis included 160 patients with compensated MASH cirrhosis from MAESTRO-NAFLD-1 who completed HRQL assessments, including the Liver Disease Quality of Life (LDQoL), Chronic Liver Disease Questionnaire-MASH (CLDQ-MASH), CLDQ-MASH Symptom Questionnaire, and Work Productivity and Activity Impairment (WPAI) questionnaires.¹ At baseline, sleep- and fatigue-related domains showed the greatest impairment.

After 52 weeks of resmetirom 80 mg, patients showed improvement in the CLDQ-MASH Worry domain (mean, +0.30; P = .001), with a trend toward improvement in LDQoL Health Distress (+3.44; P = .051). Improvements in both domains were more pronounced among patients with portal hypertension.¹

Patients achieving a relative decrease of at least 25% in liver stiffness by vibration-controlled transient elastography (VCTE) reported improvement in bleeding gums and joint pain symptoms. The authors concluded resmetirom was associated with modest but significant improvements in mental health distress and worry, as well as relief of specific symptoms.¹

Younossi noted the findings extend earlier analyses. Previous MAESTRO-NAFLD-1 data showed improvements in Worry and Health Distress scores among patients with and without cirrhosis. Additionally, prior MAESTRO-NASH data linked histologic response to HRQL gains in noncirrhotic MASH.^2,3

What Do PROs Add to MASH Treatment Decisions?

Younossi said the link between liver stiffness response and symptom improvement offers clinicians added confidence in the real-world benefit of fibrosis-directed therapy. He emphasized the goal of treatment extends beyond surrogate markers to how patients feel and how long they live.

“Patients should feel better and should live longer, right? So it’s about quality of life and quantity of life,” Younossi said.

He also highlighted the absence of worsening in HRQL domains without improvement as a signal of tolerability, contrasting resmetirom with interferon-based hepatitis C therapy, which substantially impaired quality of life. Younossi cautioned year-long trials remain short for capturing the full effect on patient-reported outcomes (PROs).

“These trials are short, even if they’re a year long. If you continue these drugs longer and you continue to improve fibrosis, I suspect the quality of life will improve even more,” he said.

In clinical practice, Younossi recommended a minimum symptom assessment focused on fatigue, distinguishing pathologic fatigue unrelieved by rest from normal fatigue. He also advised screening for comorbidities such as depression, which can overlap with fatigue.

Resmetirom is approved by the US Food and Drug Administration for adults with noncirrhotic MASH and moderate to advanced fibrosis (F2–F3). MAESTRO-NAFLD-1 was a 52-week phase 3 safety trial including an open-label cohort of patients with compensated MASH cirrhosis.⁴

Editors’ Note: Younossi reports relevant disclosures with Intercept, Boehringer Ingelheim, Ipsen, BMS, GSK, Novo Nordisk, Madridgal, Merck, Aligos, Akero, Sanofi, and others.

References:

1. Younossi Z, Nader F, Taub R, et al. Impact of resmetirom on health-related quality of life, work productivity, and disease-specific symptoms in compensated MASH cirrhosis. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Younossi Z. Health-related quality of life improvements with resmetirom, with Zobair Younossi, MD, MPH. HCPLive. Published November 11, 2025. Accessed November 6, 2026. https://www.hcplive.com/view/health-related-quality-life-improvements-resmetirom-zobair-younossi-md-mph

3. Younossi Z. Zobair Younossi, MD, MPH: resmetirom’s impact on health-related quality of life in MASH. HCPLive. Published October 9, 2024. Accessed November 6, 2026. https://www.hcplive.com/view/zobair-younossi-md-mph-resmetirom-impact-health-related-quality-life-mash

4. Harrison SA, Taub R, Neff GW, et al. Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2023;29(11):2919-2928. doi:10.1038/s41591-023-02603-1