DAY 1: Translating Targeted Therapies for Metabolic Dysfunction-Associated Steatohepatitis Into Real-World Uptake Poses Significant Challenges

The real-world uptake of resmetirom remains low more than 1 year after the medication received regulatory approval in the United States for the treatment of adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced fibrosis, according to retrospective data presented at the 2026 Annual Scientific Meeting of the American College of Gastroenterology in Nashville, Tennessee.

In a cross-sectional analysis of data included in ambulatory electronic health records after March 2024, researchers at the Cleveland Clinic in Florida analyzed resmetirom prescribing patterns to identify potential gaps in the real-world implementation of MASH therapies. The analysis showed that less than 2% of nearly 13,000 patients diagnosed with MASH or metabolic dysfunction-associated steatotic liver disease (MASLD) were prescribed resmetirom since the March 2024 regulatory approval. Moreover, prescription rates remained low even in the highest risk categories, as determined by the Fibrosis-4 (FIB-4) index, suggesting that biomarker-based risk stratification was not strongly reflected in treatment utilization. 

Patients who had been diagnosed with MASH before resmetirom became available for this indication had higher prescription rates than newly diagnosed patients (1.84% vs. 1.34%), with a median of 190 days lapsing from new diagnosis to first prescription. Most prescriptions (80%) originated from gastroenterology practices, while primary care prescriptions accounted for only 4% of the total prescriptions. 

“Our findings demonstrate [reduced] real-world uptake of resmetirom despite its availability, with prescribing concentrated in gastroenterology and limited [prescriptions originating] in primary care,” said author Tasneem Jamal Al-Din, MD, a research fellow at the Cleveland Clinic in Florida. “These findings highlight gaps in patient identification, fibrosis assessment, treatment access, and coordination between primary care and specialty care.” She noted that racial disparities contribute to the prescription gap, as does delayed initiation of therapy. The analysis revealed racial disparities in prescription patterns, with higher prescription rates observed among white patients (1.7%) compared to black patients (0.8%). “Electronic health record-based eligibility workflows, structured primary care pathways, and targeted access interventions are needed to improve uptake in this high-risk population,” Jamal Al-Din added. 

In a separate retrospective analysis of nearly 13,000 people with MASH or MASLD, the research team looked at the efficacy of risk scores such as the FIB-4 index in identifying patients with advanced MASH-related fibrosis and their impact on prescribing decisions. The study showed that FIB-4 alone missed cases of advanced fibrosis, leading to undertreatment and treatment delays. 

The FIB-4 index is a low-cost, first-line tool for ruling out advanced liver fibrosis, but it has several well-documented clinical limitations. Because the score relies mathematically on age, platelet count, and liver enzyme measurements, any condition or demographic factor that independently skews these variables can distort the results. Vibration-controlled transient elastography (VCTE or Fibroscan) provides liver stiffness measurements (LSM) and measures the controlled attenuation parameter (CAP), which help stage fibrosis and quantify steatosis. In comparing FIB-4 and VCTE data, Jamal Al-Din and colleagues found that FIB-4 missed a substantial proportion of patients with LSM-confirmed advanced fibrosis, and that many patients who met VCTE eligibility criteria remained untreated. Among the 564 patients who had both FIB-4 and LSM data, 119 (21.1%) had LSM-confirmed advanced fibrosis (stage F3 or F4) despite being assigned low or intermediate FIB-4 scores. These patients represented 63.3% of the advanced fibrosis cases identified by VCTE.
 
Resmetirom prescription rates were higher for patients who underwent VCTE (5.5%) than for the overall cohort (1.56%). However, the analysis showed that only 10% of the patients who were eligible according to the combined VCTE criteria were prescribed resmetirom, pointing to a potential gap between patient eligibility and treatment utilization. 
“FIB-4 alone may miss a substantial proportion of patients with advanced fibrosis,” Jamal Al-Din concluded, noting that “even among patients identified by VCTE as having significant fibrosis and steatosis, treatment uptake remained limited.” The integration of VCTE measurements into care pathways for MASH and MASLD may boost the identification of patients with advanced fibrosis who could benefit from therapy.