Sequential FIB-4-based testing limits detection of fibrotic MASLD despite optimized ELF thresholds

Area of Science:

• Hepatology
• Diagnostic Accuracy
• Noninvasive Biomarkers

Background:

• Current guidelines recommend sequential noninvasive testing for metabolic dysfunction-associated steatotic liver disease (MASLD).
• The Fibrosis-4 (FIB-4) index (≥1.3) acts as a gatekeeper to second-line Enhanced Liver Fibrosis (ELF) score assessment (<7.7).
• The diagnostic yield of this sequential pathway for detecting fibrotic MASLD is not well-established.

Purpose of the Study:

• To evaluate the performance of guideline-recommended sequential testing for fibrotic MASLD.
• To compare sequential versus concurrent testing strategies.
• To identify optimized ELF score thresholds for alternative diagnostic pathways.

Main Methods:

• Prospective study involving 186 patients with or at risk for MASLD.
• Patients underwent FIB-4, ELF testing, magnetic resonance elastography (MRE), and liver biopsy.
• Diagnostic performance was assessed for sequential (FIB-4 followed by ELF) and concurrent (FIB-4 or ELF) strategies.

Main Results:

• Fibrotic MASLD was present in 38% of participants.
• The guideline-recommended sequential strategy using FIB-4 ≥1.3 excluded 43% of fibrotic MASLD cases due to low FIB-4 sensitivity (57%).
• A concurrent strategy using FIB-4 ≥1.3 or ELF ≥9.4 achieved 87% sensitivity and 64% specificity for fibrotic MASLD detection.

Conclusions:

• Sequential FIB-4-based testing significantly limits the detection of fibrotic MASLD due to sensitivity constraints.
• Concurrent first-line testing with FIB-4 and ELF enhances case identification.
• Optimizing noninvasive testing pathway design is crucial for effective fibrotic MASLD assessment.