Early Liver Fat Changes Predict Resmetirom Response in MASH

Early reductions in liver fat measured by MRI-proton density fat fraction (MRI-PDFF) predicted biopsy-confirmed MASH resolution and fibrosis improvement with resmetirom, according to a MAESTRO-NASH analysis presented at The Liver Meeting 2026 in Denver, Colorado. Parvez Mantry, MD, says the findings reflect a shift already under way in practice.¹

“About 95 percent of the time or so we can use non-invasive tests to make a reliable diagnosis of the severity of MASH, and then use it serially for monitoring,” Mantry, medical director of the Liver Institute Research and the Hepatobiliary Tumor Program at Methodist Health System in Dallas, Texas, told HCPLive.

What Did the MAESTRO-NASH Analysis Show?

Resmetirom (Rezdiffra) received FDA approval after the phase 3 MAESTRO-NASH trial showed higher rates of MASH resolution and fibrosis improvement than placebo at 52 weeks in patients with F2 or F3 fibrosis.² In the new analysis, a 30% or greater reduction in MRI-PDFF at weeks 16 and 52 was strongly associated with biopsy response, with roughly 6.5-fold higher odds of MASH resolution at week 52 among responders treated with resmetirom.¹ Patients receiving resmetirom were also far more likely than those receiving placebo to achieve that liver fat response (odds ratio, 12.4 at week 16).¹ Reductions in ALT, liver stiffness by magnetic resonance elastography, and PRO-C3 also correlated with fibrosis improvement.¹

Mantry notes that fat is the central driver of inflammation and fibrosis in MASH. That makes liver fat an especially informative marker for a drug that works by improving hepatic fat metabolism.

How Should Clinicians Monitor Response?

In practice, Mantry and colleagues use noninvasive tests at 6 months and 1 year, comparing transient elastography readings with baseline to judge stability or improvement. Biopsy remains useful when noninvasive tests are discordant, he adds.

Watch the full interview to hear Mantry discuss how sharing early results affects patient adherence, when to consider stopping therapy, and what validation is still needed before noninvasive monitoring becomes standard.

Mantry has no relevant disclosures.

References

1. Loomba R, Taub R, Padmanabhan K, et al. Early and week 52 biomarker (MRI-PDFF, ALT, MRE and PRO-C3) responses to resmetirom predict improvements in MASH and liver fibrosis. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000