Authors advocate for longer duration and composite non-invasive endpoints in biopsy-free MASH trials

Metabolic dysfunction-associated steatohepatitis (MASH), progressing to cirrhosis and hepatocellular carcinoma (HCC), poses a significant global health burden. Traditional diagnosis and endpoint assessment rely on liver biopsy, which is invasive, costly, and not widely utilized in routine clinical practice. This creates a critical gap in identifying and monitoring patients, hindering the development and evaluation of effective therapies. Non-invasive tests (NITs) offer a promising alternative for patient identification and tracking disease progression.

In this authors' reply, the researchers addressed prior commentary regarding the design of MASH clinical trials. They specifically advocated for the integration of longer trial durations and the adoption of composite non-invasive test (NIT) endpoints. Their argument centered on the need for trial methodologies that better reflect real-world clinical progression and improve the feasibility of large-scale studies, particularly in the context of biopsy-free approaches.

The authors argued that current MASH trial designs, often relying on liver biopsy for primary endpoints, face practical limitations. They recommended that future trials incorporate longer durations to capture clinically meaningful disease progression, moving 'beyond feasibility' to demonstrate sustained efficacy. Furthermore, they emphasized the utility of composite NIT endpoints as a more practical and scalable alternative to biopsy, particularly for identifying patients with at-risk MASH and monitoring therapeutic response. This approach aims to accelerate drug development by facilitating larger, more accessible trials.