Association between the Fibrosis-4 index and stroke and related outcomes: a meta-analysis.

OBJECTIVE: This meta-analysis evaluated the associations between the Fibrosis-4 index (FIB-4) and overall stroke, ischemic stroke, hemorrhagic outcomes, poor functional outcome, and all-cause mortality. METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to November 4, 2025. Cohort and cross-sectional studies evaluating categorical or continuous FIB-4 were eligible. Quantitative syntheses were stratified by outcome, FIB-4 modeling approach, and effect measure, with odds ratios (ORs) and hazard ratios (HRs) analyzed separately. Prediction intervals were calculated for random-effects analyses containing at least three independent estimates. RESULTS: Twenty-two studies, including 20 cohort studies and two cross-sectional studies, were included, of which 20 contributed to at least one quantitative synthesis. Elevated categorical FIB-4 was associated with greater odds of overall stroke (OR = 1.86, 95% CI: 1.63-2.14), ischemic stroke (OR = 2.03, 95% CI: 1.72-2.40), symptomatic intracranial hemorrhage (OR = 2.52, 95% CI: 1.79-3.53), poor functional outcome (OR = 2.88, 95% CI: 2.47-3.35), and all-cause mortality (OR = 2.98, 95% CI: 2.51-3.53). Continuous FIB-4 was also associated with overall stroke (HR = 1.08, 95% CI: 1.02-1.14), symptomatic intracranial hemorrhage (OR = 1.33, 95% CI: 1.20-1.48), poor functional outcome (OR = 1.26, 95% CI: 1.11-1.43), and all-cause mortality (HR = 1.08, 95% CI: 1.03-1.12). However, prediction intervals crossed the null for the continuous analyses of poor functional outcome and all-cause mortality, and the categorical overall-stroke analysis was exploratory. CONCLUSION: Higher FIB-4 was associated with stroke and adverse stroke-related outcomes across several observational analyses. FIB-4 may provide adjunctive risk information, but prospective validation and formal assessment of its incremental clinical value are required before routine implementation. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/search, identifier: CRD420251207801.