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 independent of genetic risk factors.

• Why it matters: Genetic variants like PNPLA3, HSD17B13, TM6SF2, MTARC1, and MBOAT7 are linked to more severe liver disease, but their influence on treatment response remains unclear, impacting personalized therapy strategies.
• What they did: The study analyzed 738 patients from the MAESTRO-NASH trial, genotyping for key risk alleles and assessing liver biopsy, MRI-PDFF, and biomarkers at baseline and Week 52 to evaluate treatment efficacy across different genetic profiles.
• The result: Resmetirom's positive effects on liver health were consistent across patients with various high-risk genotypes, suggesting its mechanism may counteract genetic predispositions and enabling broader therapeutic application.