Improvement in Health-Related Quality of Life After Treatment With Resmetirom in Cirrhotic and Noncirrhotic Patients With MASLD: Data From MAESTRO-NAFLD-1

Metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH are associated with significant impairments in health-related quality of life (HRQL), particularly in patients with advanced fibrosis.¹ The MAESTRO-NAFLD-1 trial evaluated resmetirom in patients with MASLD cirrhosis (MASH cirrhosis) or MASLD without cirrhosis (early MASH).² In the early MASH cohort (VCTE 5.5 up to 8.5 kPa or MRE 2.0 up to 4.0 kPa), 1143 patients were enrolled into a double-blind arm of resmetirom 100 mg (n=325), resmetirom 80 mg (n=327), or placebo (n=320), or an open-label arm of resmetirom 100 mg (n=171). The MASH cirrhosis cohort included 180 patients with well-compensated MASH cirrhosis with no history of decompensation who received open-label resmetirom 80 mg. The median age of patients in the early MASH cohort was 56 years; 43% were male, 53% had T2DM, and the median MRI-PDFF was 18%. The median age of patients in the MASH cirrhosis cohort was 61 years; 38% were male, 73% had T2DM, and the median MRI-PDFF was 9%.

In this study, treatment of MASLD was associated with improved HRQL, especially in patients who had improvement with MRI-PDFF. This suggests that it is the treatment of disease that is improving how patients feel. Despite the GI side effects associated with resmetirom, abdominal symptoms significantly improved. When patients report feeling better, this could be from reducing hepatomegaly. Essentially, the results show how preventing disease progression is vital to this population, as this decreases the concern patients have about becoming ill from this progressive disease.

—Nancy S. Reau, MD

Younossi and colleagues reported on the effects of resmetirom treatment on HRQL in patients with MASLD with and without cirrhosis enrolled in the MAESTRO-NAFLD-1 trial.³ HRQL was assessed using the 17-domain Liver Disease Quality of Life (LDQOL) questionnaire and the 6-domain Chronic Liver Disease Questionnaire–non-alcoholic fatty liver disease (CLDQ-NAFLD). At baseline, HRQL scores in patients with MASH cirrhosis were significantly lower than those of patients with early MASH. In the early MASH cohort, after no differences were found between the double-blind resmetirom arm and the open-label resmetirom arm, the two groups were pooled for subsequent analyses.

In patients with early MASH, 52 weeks of resmetirom was associated with significant improvements over placebo in abdominal symptoms, worry, and health distress scores, and appeared to reduce the extent of declines in physical and emotional role functioning. Patients who attained a 30% or greater reduction in MRIPDFF after 52 weeks of resmetirom had greater improvements in the Worry and Abdominal Symptoms domains of CLDQ-NAFLD and the Stigma from liver disease domain of the LDQOL than patients in the placebo arm or nonresponders (Figure 3).

Figure 3.

Selected health-related quality-of-life scores in patients with early metabolic dysfunction-associated steatohepatitis who achieved a 30% or more reduction in magnetic resonance imaging–proton density fat fraction (from baseline by week 52) with resmetirom treatment vs nonresponders and placebo in the MAESTRO-NAFLD-1 trial.

CLDQ-NAFLD, Chronic Liver Disease Questionnaire–Non-Alcoholic Fatty Liver Disease; LDQOL, Liver Disease Quality of Life instrument.

Adapted from Younossi ZM, et al. AASLD abstract 0181. Presented at: The Liver Meeting; November 7-11, 2025; Washington, DC.³

Across all domains, HRQL scores were lower in patients with cirrhosis than in patients with early MASH and in patients with biopsy-proven F2 to F3 MASH (per historic data in the MAESTRO-NASH trial).⁴ The greatest impairments were observed in the Worry, Health Distress, Role Physical, Hopelessness, Physical Functioning, and General Health domains. Among patients with MASH cirrhosis, resmetirom was associated with improvements in the Worry domain of the CLDQ-NAFLD and the Health Distress domain of the LDQOL by week 24, and these improvements were sustained out to year 2 (P<.05). Significant improvements in the Stigma score were observed in patients with MASH cirrhosis with a PDFF response at week 52 (P<.05).

Resmetirom was associated with improvements in selected HRQL scores in patients with MASH cirrhosis and those with early MASH, and these benefits were sustained long-term. The findings suggest that resmetirom addresses patient-reported outcomes in patients with MASLD.

ABSTRACT SUMMARY A Phase 2, Multicenter, Randomized, Placebo-Controlled Trial of Pemvidutide in MASH.

Pemvidutide is a 1:1 glucagon/GLP-1 dual receptor agonist that was designed with a pharmacokinetic profile to enhance tolerability. The efficacy of pemvidutide in patients with F2/F3 MASH was evaluated in the phase 2b multicenter, randomized, placebo-controlled IMPACT trial (Abstract 5001). A total of 212 patients were randomly assigned to pemvidutide 1.2 mg (n=41), 1.8 mg (n=85), or placebo (n=86) weekly. At week 24, MASH resolution without worsening of fibrosis was attained in 58% of patients at the 1.2-mg dose and 52% at the 1.8-mg dose, compared with 20% with placebo. Multiple fibrosis biomarkers were significantly improved with pemvidutide, including FAST score, ELF, LSM, and PRO-C3, as were the liver injury and inflammatory biomarkers ALT, AST, and corrected T1. Liver fat content was significantly reduced with pemvidutide at 24 weeks and weight loss of up to 5.8% occurred. GI toxicities were primarily mild or moderate and included nausea (up to 41.2%), diarrhea (up to 21.2%), constipation (up to 12.9%), and vomiting (up to 8.2%). One patient discontinued pemvidutide compared with 2 patients on placebo.