A 45-year-old woman with no alcohol history, BMI 34, type 2 diabetes and hypertension has elevated transaminases. Liver biopsy shows hepatocyte ballooning, lobular inflammation, pericellular fibrosis and Mallory-Denk bodies. FIB-4 score is 3.2. The diagnosis is NASH with advanced fibrosis. Which recently FDA-approved (2024) agent directly targets hepatic steatosis and fibrosis in NASH/MAFLD?
- A Metformin
- B Vitamin E
- C Resmetirom (thyroid hormone receptor-beta agonist) ✓
- D Orlistat
Explanation
Resmetirom (Rezdiffra) is the first FDA-approved pharmacotherapy specifically for NASH (now termed metabolic dysfunction-associated steatohepatitis, MASH) with moderate-to-advanced liver fibrosis (F2–F3), approved in March 2024 based on the MAESTRO-NASH trial. It is a liver-targeted thyroid hormone receptor-beta (THR-β) agonist that reduces hepatic triglyceride synthesis and steatosis, achieving NASH resolution and fibrosis improvement. Metformin has no proven anti-fibrotic benefit in NASH. Vitamin E (PIVENS trial) benefits non-diabetic non-cirrhotic NASH but is not approved. Orlistat promotes weight loss without direct hepatic action.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.