ArticleHepatology communications2026
Sequential FIB-4-based testing limits detection of fibrotic MASLD despite optimized ELF thresholds.
Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSocietal guidance recommends sequential noninvasive testing for metabolic dysfunction-associated steatotic liver disease (MASLD), using Fibrosis-4 (FIB-4) ≥1.3 as a gatekeeper before second-line assessment with the Enhanced Liver Fibrosis (ELF) score (<7.7 as a rule-out). The impact of this pathway design on the detection of fibrotic MASH remains uncertain. We aimed to evaluate the performance of guideline-endorsed sequential testing and to determine optimized ELF thresholds within alternative strategies.
methodsIn this prospective study, patients with or at risk for MASLD underwent FIB-4, ELF testing, magnetic resonance elastography (MRE), and liver biopsy within 1 month. Fibrotic MASLD was defined as fibrosis stage ≥2 on histology or liver stiffness ≥3.1 kPa on MRE. Diagnostic performance of ELF was assessed, and sequential (ELF applied after FIB-4 ≥1.3) and concurrent (either test positive) testing strategies were compared.Results:Among 186 participants (median age 51 years; 69% women), fibrotic MASLD was present in 71 (38%). ELF demonstrated AUROC 0.77 (95% CI 0.70-0.84); the cohort-derived cutoff was 9.4 (80% sensitivity, 65% specificity). Lower cutoffs (8.7 and 7.7) increased sensitivity (≥90% and 100%) but low specificity (34% and 4%). FIB-4 ≥1.3 showed limited sensitivity (57%), resulting in 43% of fibrotic MASH cases being excluded from second-line testing. Sequential application of ELF, therefore, failed to overcome this sensitivity ceiling. A concurrent strategy using FIB-4 ≥1.3 or ELF ≥9.4 improved sensitivity to 87% with 64% specificity.
conclusionsSequential FIB-4-based testing substantially limits the detection of fibrotic MASLD due to gatekeeping sensitivity constraints. Concurrent first-line testing with FIB-4 and ELF improves case identification, underscoring the importance of pathway design in optimizing noninvasive fibrosis assessment.
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