Understanding Why Metabolic-Dysfunction-Associated Steatohepatitis Lags Behind Hepatitis C in Therapeutic Development and Treatment Advances

Therapeutic development for metabolic-dysfunction-associated steatohepatitis (MASH) trails behind the success seen in hepatitis C virus (HCV) management. HCV, characterized by a viral etiology, benefits from direct-acting antivirals (DAAs) targeting viral proteins, achieving cure rates exceeding 90%. In contrast, MASH involves complex metabolic, genetic, and environmental factors, presenting challenges for drug development. Non-invasive diagnostics like ultrasound, FibroScan, and serum biomarkers, while increasingly used, lack the diagnostic accuracy of liver biopsy, the current gold standard. This review evaluates therapies for MASH, including resmetirom (Rezdiffra) and combinations like pioglitazone and vitamin E, which show potential but offer modest improvements due to MASH’s heterogeneity. The limited efficacy of these treatments highlights the need for multi-targeted strategies addressing metabolic and fibrotic components. Drawing parallels to HCV’s success, this review emphasizes advancing diagnostics and therapies for MASH. Developing effective, patient-specific therapies is crucial to closing the gap between MASH and better-managed liver diseases, optimizing care for this growing health challenge.