Presentation (CTI)

OBJECTIVES: Metabolic dysfunction-associated steatohepatitis (MASH) is associated with progressive fibrosis, cirrhosis, liver-related complications, impaired quality of life, and increasing healthcare resource use. With emerging pharmacological therapies, this review aimed to characterise the current evidence base and identify key evidence gaps relevant to access decision-making across United Kingdom, France, Germany and the United States.
METHODS: A targeted literature review was conducted across various published sources. Evidence was extracted across epidemiology, disease burden, unmet need, diagnosis, HTA reports, regulatory and reimbursement status, economic evidence, patient-reported outcomes, and pivotal Phase II/III trials of resmetirom, semaglutide, tirzepatide, and retatrutide. Evidence gaps were identified by mapping available evidence against HTA-relevant decision domains.
RESULTS: Across markets, MASH was associated with substantial and increasing clinical and economic burden, with costs concentrated in advanced fibrosis, cirrhosis, and liver-related complications, supporting the potential value of earlier intervention. However, underdiagnosis remained a consistent challenge, particularly among patients with moderate-to-advanced fibrosis, while variations in the use and reimbursement of non-invasive tests such as FIB-4, ELF, and FibroScan may limit identification of eligible populations. Pivotal trials demonstrated clinically meaningful effects across liver-directed and metabolic treatment approaches, but heterogeneity in endpoints, trial duration, populations, and comparator strategies may increase uncertainty in comparative effectiveness and economic evaluation.
CONCLUSIONS: The MASH evidence base is rapidly evolving, but HTA readiness remains limited by diagnostic fragmentation and uncertainty linking short-term histological or metabolic endpoints to long-term outcomes. To support future HTA and reimbursement decisions, evidence generation should prioritise appropriate identification of eligible F2-F3 patients, validation of surrogate endpoints, prevention or delay of disease progression, quality-of-life impact, reduction of healthcare resource utilisation, and the comparative effectiveness and value of liver-directed versus metabolic treatment strategies.