Two-year data from a multicenter study presented at the American College of Gastroenterology Scientific Meeting suggest that resmetirom, a thyroid hormone receptor beta agonist, may improve portal hypertension and liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis.

Presented by Naim Alkhouri, MD, director of the Steatotic Liver Disease Program at Summit Clinical Research in Phoenix, Arizona, this oral abstract won the ACG Governors Award for Excellence in Clinical Research.

The analysis included 122 patients with Child Pugh A MASH cirrhosis and assessed changes in noninvasive biomarkers, liver stiffness, and clinically significant portal hypertension (CSPH).

Patients received 80 mg of resmetirom for up to 2 years as part of the MAESTRO-NAFLD-1 study and its open-label extension. CSPH was defined according to Baveno VII criteria, incorporating FibroScan vibration-controlled transient elastography (VCTE), platelet count, and magnetic resonance elastography (MRE).

At baseline, 63% of patients met probable or definitive CSPH criteria. Following treatment, 20% no longer met CSPH criteria at 1 year, increasing to 28% at 2 years. Additionally, 35% of patients with confirmed F4 fibrosis at baseline demonstrated regression to F3 by year 2, defined as VCTE <15 kPa and ≥25% reduction from baseline.

“Resmetirom demonstrated significant improvements in noninvasive biomarkers, liver stiffness on imaging and portal hypertension risk in patients with MASH cirrhosis,” the authors reported. The discontinuation rate was low (8%), and the most frequent adverse events were mild gastrointestinal disorders.

These results reinforce resmetirom’s therapeutic potential beyond earlier-stage disease. “Resmetirom was safe and well-tolerated in this population,” the authors concluded, noting that these findings support further validation in the ongoing MAESTRO-NASH OUTCOMES trial, which is evaluating clinical outcomes in 845 patients with MASH cirrhosis.

Reference
Alkhouri N, Taub R, Labriola D, Lu X, Moussa S, Noureddin M. Treatment with resmetirom for up to two years led to improvement in liver stiffness, fibrosis biomarkers, fibrosis scores, and portal hypertension risk in 122 patients with compensated MASH cirrhosis. Presented at: American College of Gastroenterology Scientific Meeting, October 24-29, 2025; Phoenix, AZ.