MASH (Metabolic-Associated Steatohepatitis): The New Treatment Landscape

From NASH to MASH: Nomenclature and Disease Burden

The transition from NASH (nonalcoholic steatohepatitis) to MASH (metabolic-associated steatohepatitis) reflects the updated nomenclature adopted in 2023, emphasizing the metabolic drivers of the disease. MASH affects an estimated 5% of the global adult population, with progression to cirrhosis, hepatocellular carcinoma, and liver-related mortality representing the primary clinical concerns.

Resmetirom: The First Approved MASH Therapy

Resmetirom (Rezdiffra), a thyroid hormone receptor beta agonist, received FDA approval in March 2024 for adults with noncirrhotic MASH and moderate to advanced fibrosis (stages F2-F3). The MAESTRO-NASH trial demonstrated MASH resolution without worsening fibrosis in 25.9% of patients at 80 mg and 29.9% at 100 mg versus 9.7% with placebo. Fibrosis improvement of one or more stages occurred in 24.2% (80 mg) and 25.9% (100 mg) versus 14.2% with placebo.

GLP-1 Agonists in MASH: Semaglutide and Tirzepatide

Semaglutide 2.4 mg weekly demonstrated MASH resolution in 59% of patients versus 17% with placebo in Phase 2 data. The SYNERGY trial showed tirzepatide achieved MASH resolution in up to 74% of patients, representing potentially the highest response rate of any investigational MASH therapy. Both agents address the metabolic comorbidities (obesity, diabetes) that drive disease progression.