GLP-1s Lower MASH Activity but Not Fibrosis: Winston Dunn, MD, FAASLD

Patients screened for metabolic dysfunction-associated steatohepatitis (MASH) trials now show less disease activity but more advanced fibrosis, and GLP-1 therapy may help explain the split, according to Winston Dunn, MD, FAASLD, professor of medicine in gastroenterology and hepatology at the University of Kansas Medical Center. Dunn presented the findings, along with SMART-MASH, a new cirrhosis screening tool, at AASLD’s The Liver Meeting 2026.

Why Fibrosis Is Rising in the GLP-1 Era

Dunn said trial protocols have become better at finding patients with fibrosis through vibration-controlled transient elastography (VCTE) and Enhanced Liver Fibrosis (ELF) testing, but no effective tool exists to identify ballooning, a marker of disease activity. Meanwhile, GLP-1 use has lowered ballooning over time.

Citing the ESSENCE trial, in which fewer patients needed treatment to achieve MASH resolution than fibrosis improvement, Dunn noted that disease activity responds faster than fibrosis. In his dataset, patients had taken GLP-1s for a median of about 1 year, likely long enough to lower NAS scores but not fibrosis. That matters for trial design. The FDA requires both MASH resolution and fibrosis improvement, though some trials enroll cohorts based on a fibrosis cutoff alone, which may suit patients already taking GLP-1s.

“The fibrosis is actually the most important predictor of clinical outcome,” he said.

A More Efficient Cirrhosis Screen

SMART-MASH uses VCTE alone in a third of patients, VCTE plus ELF in another third and point-of-care labs in the rest, conserving costly or less available tests. Compared with Agile 4, it had a higher area under the curve and identified about a third more patients with cirrhosis, who face higher risk of major adverse liver outcomes and may need liver cancer and portal hypertension surveillance.

“So it can save resources and it can identify additional patients at the same time,” Dunn said.