Defining Noninvasive Criteria for Indicating Drug Therapy in Metabolic Dysfunction-associated Steatotic Liver Disease...

Resmetirom is the first Food and Drug Administration-approved drug for metabolic dysfunction-associated liver disease (MASLD) in F2 and F3 patients with steatohepatitis. Noninvasive criteria have been proposed for initiating treatment; however, these have not been validated in clinical practice. We validated the proposed criteria and established new guidelines for initiating resmetirom treatment in clinical practice.

This was a cross-sectional study of 1281 MASLD patients from the HEPAmet registry with biopsy, comorbidity assessment, analytical profile, and elastography. Identification of MASLD with F2 and F3 was the main endpoint. A comprehensive review of international guidelines and expert consensus up to November 2024, focusing on therapeutic indications, was conducted.

A total of 38% (n = 486 of 1281) of patients were diagnosed with MASLD F2 and F3 based on biopsy. However, only 39% and 56% of them met treatment eligibility criteria according to the Expert Panel Criteria and the American Association for the Study of Liver Diseases Practice Guidance, respectively. They included 45% of patients with early-stage fibrosis. False positive and false negative rates ranged from 23% to 41% and 44% to 60%, respectively, with area under the receiver-operating characteristic curve values below 0.60.These findings were validated in an external cohort. A two-step strategy, first selecting patients with Fibrosis-4 (FIB-4) ≥1.30, or with diabetes and overweight if FIB-4 <1.30, followed by a liver stiffness between 8 and 25 kPa, demonstrated higher positive (55%) and negative predictive values (77%) and higher area under the receiver-operating characteristic curve (0.67).This approach successfully identified 74% of the target population.

The diagnostic performance and reliability of the proposed noninvasive criteria for initiating resmetirom treatment were suboptimal. About the half of patients with indication would not receive treatment under these criteria. A new strategy, using FIB-4, the presence of diabetes and overweight, and liver stiffness improved the identification of MASLD patients with F2 and F3.