Resmetirom and MASLD Spectrum: Hepatology Communi — March 2026

Introduction

Metabolically associated steatotic liver disease (MASLD) has become one of the most common causes of chronic liver disease worldwide, closely linked to the global epidemics of obesity and type 2 diabetes. The progressive form, metabolic dysfunction–associated steatohepatitis (MASH), can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and liver transplantation. Until recently, treatment options were limited mainly to lifestyle modification. Resmetirom, a selective thyroid hormone receptor-β (THR-β) agonist, represents a new pharmacologic therapy targeting hepatic steatosis and inflammation and is now approved for MASH with F2–F3 fibrosis. Beyond histologic improvements, its effect on health-related quality of life (HRQL) across the MASLD spectrum remained uncertain.

Summary

This analysis from the MAESTRO-NAFLD-1 trial and its open-label extension evaluated HRQL outcomes in patients with early MASH and MASH cirrhosis treated with resmetirom. A total of 1143 patients with early MASH and 180 with MASH cirrhosis were included. HRQL was assessed using disease-specific instruments, including CLDQ-NAFLD and LDQoL.

Patients with MASH cirrhosis had significantly poorer baseline quality-of-life scores compared with those with earlier disease. Treatment with resmetirom (80–100 mg) resulted in meaningful improvements in several HRQL domains, particularly worry, abdominal symptoms, and health distress, beginning by week 24 and sustained through week 52 and into year 2. Improvements were more pronounced in patients who achieved MRI-PDFF response, indicating a reduction in hepatic fat.

Overall, the study demonstrates that resmetirom not only improves liver pathology but also enhances disease-specific quality of life in patients across the MASLD spectrum, including those with cirrhosis, supporting its broader clinical benefit beyond histologic endpoints.