Non-invasive tests for resmetirom treatment fail to accurately define the target population: Evidence from a biopsy-proven MASLD cohort

Abstract

Background and Aim: Resmetirom received conditional Food and Drug Administration (FDA) approval in 2024 for metabolic dysfunction-associated steatotic liver disease (MASLD) based on its promising liver-targeted therapy. Clinical trials required a histological diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) with F2-F3 fibrosis, excluding cirrhosis, while real-world prescribing relies on non-invasive tests (NITs). This study evaluates their efficacy in identifying the target population within a biopsy-proven Turkish MASLD cohort. Materials and Methods: We analyzed 266 patients with biopsy-proven MASLD from the Turkish NAFLD Biobank. Inclusion required AST >17 U/L (females) or >20 U/L (males), and CAP ≥280 dB/m. Eligibility was defined by liver stiffness measurement (LSM) of 10–19.9 kPa (excluding cirrhosis or low platelet count) or a FAST score ≥0.67. Results: Among the study population, 130 patients (48.9%) had histologically confirmed MASH with F2-F3 fibrosis. Based on LSM criteria applied to histologically eligible patients, 81 patients (62.3%) were underdiagnosed, compared to 95 patients (73.1%) when using the FAST score. Additionally, among patients who corresponded to NIT, 34 patients (41.0%) were overprescribed using LSM, while 23 patients (39.7%) were overprescribed using the FAST score. The kappa value as a measure of agreement showed poor compatibility for both LSM and FAST with liver biopsy (0.128 and 0.101, respectively). When treatment decisions were guided by either of the NITs, 44 patients (44.0%) received unnecessary prescriptions, and 74 patients (44.6%) had missed diagnoses. Conclusion: The NITs defined for identifying the target population for resmetirom demonstrated poor performance in accurately detecting or ex cluding eligible patients. Therefore, performing a liver biopsy before starting resmetirom treatment will prevent unnecessary increases in cost and significantly reduce the economic burden of the treatment.