Cost-Effectiveness of Blood-Based Fibrosis Screening in High-Risk Metabolic Liver Diseases With Emerging Therapies

Metabolic dysfunction-associated steatotic liver disease (MASLD) remains a global public health threat. With emerging effective pharmacologic therapies, early identification of significant fibrosis in primary care is critical. We evaluated the cost-effectiveness of blood-based noninvasive tests incorporating real-world diagnostic performance in the contemporary MASLD treatment era.

We developed a decision-analytic model for MASLD natural history and treatment to compare 6 noninvasive test strategies using Fibrosis-4 (FIB-4) and/or enhanced liver fibrosis (ELF) tests at varying cutoffs. Patients identified with significant fibrosis were referred for hepatology staging (biopsy and/or imaging-based), and eligible individuals were considered for Resmetirom ($47,400/y; mean duration: 1.6-1.8 year). Model parameters were informed by a real-world cohort (n = 400) of high-risk primary care patients with suspected MASLD who underwent both tests. Outcomes included quality-adjusted life-years (QALYs), lifetime costs, incremental cost-effectiveness ratios, and adverse liver outcomes averted.

The modeled population had a mean age of 64 years, mean body mass index of 32 kg/m², with 82% having type-2 diabetes and 15% significant fibrosis. Sequential screening with ELF (cutoff 9.80) following indeterminate FIB-4 (1.3-2.67) was the most cost-effective, yielding 8.610 QALYs and $96,990 in lifetime costs at a $100,000/QALY threshold. ELF-alone screening at a 9.00 cutoff maximized QALYs and individuals treated but increased unnecessary referrals. Resmetirom cost was most influential on results: if cost fell below $11,570/y (base case, $47,400/y), ELF-alone screening became the preferred strategy. Findings remained robust across sensitivity analyses, including in low-risk populations.

By integrating real-world diagnostic performance with new MASLD therapies, this translational modeling study identifies a scalable, cost-effective fibrosis screening pathway using FIB-4 and ELF. These findings support implementation of blood-based fibrosis screening in general primary care populations.