Effects of MASH risk genotypes on resmetirom efficacy in patients with MASH and fibrosis.

Resmetirom improves MASH resolution and fibrosis in non-cirrhotic patients regardless of high-risk MASH genotypes, with effects consistent across genetic profiles.

• Why it matters: Genetic variants like PNPLA3, HSD17B13, TM6SF2, MTARC1, and MBOAT7 are linked to increased susceptibility and severity of MASH and related liver diseases, but their influence on treatment response remains unclear.
• What they did: The study analyzed 738 patients from the MAESTRO-NASH trial, genotyping for key risk alleles, and assessed liver biopsy, MRI-PDFF, and biomarker responses at baseline and Week 52, comparing resmetirom versus placebo.
• The result: Resmetirom's positive effects on MASH, fibrosis, and hepatic steatosis were not significantly affected by the presence of common MASH risk genotypes, suggesting its mechanism may counteract genetic risk factors.