Nutr Metab Cardiovasc Dis. 2026 Sep 28:105008. doi: 10.1016/j.numecd.2026.105008. Online ahead of print.
ABSTRACT
AIM: MASLD/NAFLD clusters with type 2 diabetes, obesity, chronic kidney disease, heart failure and atherosclerotic cardiovascular disease. The Fibrosis-4 index (FIB-4), a simple blood-based marker of liver fibrosis, may also identify a broader high-risk cardiometabolic phenotype. We aimed to evaluate whether an elevated FIB-4 is associated with all-cause mortality in adults with MASLD/NAFLD and/or cardiometabolic-risk conditions.
DATA SYNTHESIS: We systematically reviewed longitudinal studies reporting FIB-4 or related blood-based liver-fibrosis non-invasive tests as prognostic markers (PROSPERO CRD420261420744). Because eligible cohorts proved non-exchangeable in population and exposure definition, the primary synthesis was a structured synthesis without meta-analysis (SWiM) restricted to MASLD, with random-effects pooling reported for reference only. The evidence map comprised 34 records. Across all cohorts, elevated FIB-4 was consistently associated with higher all-cause mortality (adjusted hazard ratio approximately 1.5-2.6, all statistically significant). A reference pool of the four MASLD studies sharing a FIB-4≥2.67 threshold (Feng, Chung, Barbosa, Ciardullo) gave a hazard ratio of 2.21 (Hartung-Knapp 95% CI 1.80-2.72; prediction interval 1.08-4.52, excluding the null) but with substantial residual heterogeneity (I2 70.8%), so no single pooled effect size is presented as primary. Heterogeneity persisted after restriction to MASLD and to a common threshold.
CONCLUSION: Elevated FIB-4 is consistently associated with higher all-cause mortality across MASLD/NAFLD and cardiometabolic populations. FIB-4 should be interpreted as an inexpensive prognostic risk enhancer and triage signal that may prompt broader cardiometabolic and liver-risk assessment, rather than as a standalone causal cardiovascular risk score.
PMID:42967849 | DOI:10.1016/j.numecd.2026.105008