Global Bivariate Meta-Analysis of FIB-4 Cut-Offs to Rule Out Advanced Fibrosis in MASLD.

Background: The fibrosis-4 (FIB-4) index, a non-invasive marker, evaluates advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), but the variability in its performance across different populations remains unclear. Methods: We conducted a systematic review and bivariate meta-analysis of 14 studies (N = 5521) with 2 × 2 contingency data for FIB-4 at thresholds < 1.0 and < 1.3, compared with liver biopsy or transient elastography (TE). The Reitsma model (R v4.4.3) estimated pooled sensitivity and specificity. Subgroup analyses assessed region (India vs. global) and reference standard effects, with heterogeneity and publication bias (Deeks' test) evaluated. Results: Pooled sensitivity was 0.73 (95% CI: 0.69-0.77), and specificity was 0.69 (95% CI: 0.61-0.76) at < 1.3. The < 1.0 threshold demonstrated higher specificity (0.83, 95% CI: 0.75-0.89) but lower sensitivity (0.63, 95% CI: 0.58-0.68). Indian cohorts (n = 3) exhibited higher specificity (0.83) than the global estimate (0.66) at < 1.3, whereas sensitivity remained similar. Conclusion: FIB-4 below 1.3 is a useful initial tool for ruling out advanced fibrosis in MASLD, with potential regional variations in specificity. Larger studies are needed to confirm cut-offs, supporting tailored guidelines with sequential testing.