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

Area of Science:

• Hepatology
• Non-invasive diagnostics
• Liver fibrosis assessment

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing concern.
• Advanced fibrosis in MASLD requires accurate detection.
• The Fibrosis-4 (FIB-4) index is a widely used non-invasive marker for advanced liver fibrosis.

Purpose of the Study:

• To systematically evaluate the diagnostic performance of the FIB-4 index for advanced fibrosis in MASLD.
• To investigate potential variations in FIB-4 performance across different populations and geographical regions.
• To compare FIB-4 performance at different diagnostic thresholds.

Main Methods:

• A systematic review and bivariate meta-analysis of 14 studies involving 5521 participants.
• Analysis of 2x2 contingency data for FIB-4 thresholds <1.0 and <1.3.
• Comparison against liver biopsy or transient elastography (TE) as reference standards.
• Subgroup analyses for regional effects (India vs. global) and heterogeneity assessment.

Main Results:

• At a FIB-4 threshold <1.3, pooled sensitivity was 0.73 and specificity was 0.69.
• At a FIB-4 threshold <1.0, sensitivity decreased to 0.63, while specificity increased to 0.83.
• Indian cohorts showed higher specificity (0.83) compared to global estimates (0.66) at <1.3, with similar sensitivity.

Conclusions:

• The FIB-4 index, particularly below 1.3, serves as a practical initial tool for excluding advanced fibrosis in MASLD.
• Observed regional variations in specificity suggest potential for tailored diagnostic approaches.
• Further large-scale studies are recommended to validate cut-offs and inform sequential testing strategies.