Meta-Analysis: Enhanced Liver Fibrosis (ELF) Test for Identifying Significant Fibrosis, Advanced Fibrosis, and Cirrhosis in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND

Non-invasive tests are increasingly employed to evaluate liver fibrosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Accurate cutoffs for significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) are critical for establishing diagnostic guidelines and qualification for MASLD-related anti-fibrotic therapy.

AIMS: Determine optimal Enhanced Liver Fibrosis (ELF) Test MASLD cutoffs for ≥F2, ≥F3, and F4 identification and decision-making, evaluate the appropriateness of guideline-recommended cutoffs, and assess ELF performance.

METHODS

Using four databases, we identified 34 MASLD-focused studies conducted between 2004 and 2026 evaluating ELF cutoffs (37 cohorts): quality was assessed using Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2). Multiple cutoffs were integrated using hierarchical summary receiver operating characteristic analysis. Sensitivity (Sens) and specificity (Spec) at Youden cutoffs and guideline-recommended cutoffs were estimated using Steinhauser's hierarchical multi-cutoff random-effects model and R diagmeta package v0.5-1.

RESULTS

Youden cutoffs (AUROCs [95% CIs]) were: ≥F2: 9.37 (0.818 [0.781-0.850]); ≥F3: 9.64 (0.818 [0.782-0.850]); F4: 9.99 (0.774 [0.711-0.827]). Sens and Spec at established cutoffs were: ≥F2 (9.00) 0.86 Sens, 0.61 Spec; ≥F3 (9.80) 0.70 Sens, 0.79 Spec; F4 (11.30) 0.21 Sens, 0.96; and F4 (10.50) 0.50 Sens, 0.86 Spec. For F2 rule-out (7.70), Sens = 0.98 and Spec = 0.14.

CONCLUSION

ELF < 9.00 may be useful to rule out ≥ F2 fibrosis in MASLD. ELF ≥ 9.80 and ≥ 11.30 represent balanced cutoffs for ≥F3 and F4 fibrosis, respectively. ELF ≥ 10.50 could represent an upper limit for MASLD-related anti-fibrotic therapeutic decision-making. ELF at 7.70 is not a meaningful cutoff for any purpose.

TRIAL REGISTRATION: PROSPERO registration: CRD420251145859.