Who Should Receive Resmetirom?: CGH | April 2026

• Resmetirom is the first FDA-approved therapy for patients with MASH/MASLD and stage F2–F3 fibrosis, creating an urgent need for reliable noninvasive methods to identify treatment candidates.
• This study evaluated whether currently proposed noninvasive treatment eligibility criteria accurately identify patients with biopsy-proven F2–F3 disease.
• The analysis included 1,281 patients from the HEPAmet registry with liver biopsy, elastography, metabolic profiling, and clinical characterization.
• Approximately 38% of patients had biopsy-confirmed F2–F3 fibrosis, representing the target population for treatment.
• Current expert panel recommendations and existing practice guidance performed poorly in real-world settings.
• Depending on the criteria used, only 39%–56% of eligible F2–F3 patients would have been identified for treatment.
• False-negative rates were particularly concerning, meaning that many patients who could potentially benefit from therapy would not receive treatment.
• Existing approaches also generated substantial false-positive rates, exposing some lower-risk patients to unnecessary therapy.
• The authors proposed a simplified two-step strategy.
• Step 1:

FIB-4 ≥1.3

OR diabetes plus overweight/obesity even if FIB-4 is <1.3

• Step 2:

Liver stiffness measurement between 8 and 25 kPa

• This strategy improved identification of patients with clinically significant fibrosis and captured approximately 74% of the target F2–F3 population.
• The model also showed better diagnostic performance than currently proposed treatment algorithms.
• The findings emphasize that reliance on a single noninvasive marker is insufficient for treatment selection in MASLD.
• Combining metabolic risk factors with fibrosis assessment provides a more clinically useful approach.
• As additional therapies for MASLD become available, accurate noninvasive treatment selection will become increasingly important.
• The study supports moving toward pragmatic clinical algorithms that can be easily implemented in routine hepatology practice.

Bottom line: Current noninvasive criteria for selecting patients for resmetirom miss a substantial proportion of biopsy-proven F2–F3 MASLD patients. A simple strategy combining FIB-4, metabolic risk factors (diabetes/overweight), and liver stiffness measurement may more accurately identify patients who are likely to benefit from treatment.