Fibrosis-Focused End Points Could Reshape MASH Trial Design: Zobair M. Younossi, MD

Building on data he presented at the European Association for the Study of the Liver Congress in May 2026, Zobair M. Younossi, MD, chairman of the Global NASH Council, addressed the practical implications of shifting metabolic dysfunction–associated steatohepatitis (MASH) trial design to use fibrosis, rather than steatohepatitis resolution, as the primary end point in part 3 of his interview with The American Journal of Managed Care^®.

Younossi identified 3 concrete changes this shift would bring to trial design. First, enrollment would become considerably easier, as trials would no longer need to confirm that all components of steatohepatitis, such as ballooning degeneration and lobular inflammation, are present at screening because this is no longer the primary end point.

Second, because fibrosis can be measured with more sophisticated and objective technologies, such as artificial intelligence–based analysis and morphometry, sponsors would be able to detect quantitative, incremental changes in fibrosis rather than relying on cruder binary assessments. This would make the end point easier to achieve and interpret, Younossi argued.

The shift also carries more than logistical benefits. Because fibrosis is closely linked to long-term outcomes, Younossi explained that meeting a fibrosis end point gives investigators greater confidence that a drug could translate into meaningful clinical benefit over time.

The third major shift would be the potential replacement of liver biopsy with validated noninvasive fibrosis biomarkers. Growing evidence suggests that these biomarkers can predict both fibrosis and downstream outcomes, he noted, positioning them as potential substitutes for biopsy in both enrollment and monitoring. This change could remove a major barrier to trial participation.

Younossi framed these developments as an early, foundational step in an ongoing dialogue with regulators about how MASH trial end points and methodology should evolve.

“It’s the first step, or one of the first steps, in terms of conversation here about what the regulatory body should do,” he concluded. “I suspect that that’s where we are slowly moving toward anyway because of validating noninvasive tests and getting more data in that context.”