Abstract
BACKGROUND: The association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) is well studied. Liver fibrosis is the main histopathologic manifestations of NAFLD. However, whether concomitant NAFLD influence the association of non-invasive liver fibrosis scores with CVD remains unclear. METHODS: We systematically searched PubMed, Cochrane Library, and Embase databases for cohort studies exploring the association between liver fibrosis score (LFS)and CVD events up to June 10, 2025. Random-effects model was used to pool results. CVD events were defined as cardiovascular mortality, myocardial infarction, and coronary heart disease. RESULTS: Nineteen cohorts involving 1,481,875 adults were included with an average age of 54.8 years old, and 50.2% males. Fibrosis 4 score (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS) and APRI (Aspartate transaminase/platelet ratio index) were associated with increased risks of CVD events (FIB-4: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.58–1.99, low certainty; NFS: OR 2.40, 95% CI 1.83–3.14, low certainty; APRI: OR 1.61, 95% CI 1.17–2.21, low certainty). Each one-unit increment in FIB-4, NFS scores was associated with CVD events (FIB-4: OR 1.21, 95% CI 1.12–1.31; NFS: OR 1.38, 95% CI: 1.17–1.62). A positive linear relationship was observed between FIB-4 (P-nonlinearity = 0.000), NFS (P-nonlinearity = 0.7145) and CVD events. Risk estimates for cardiovascular events were similar in patients with NAFLD (FIB-4: OR 1.87, 95% CI 1.53–2.28; NFS: OR 2.59, 95% CI 1.55–4.33) and without NAFLD (FIB-4: OR 1.74, 95% CI 1.51-2.00; NFS: OR 2.26, 95% CI 1.64–3.11) (P for difference: FIB-4 = 0.56; NFS = 0.66). CONCLUSION: FIB-4 and NFS were associated with an increased risk of CVD events in patients with and without NAFLD. FIB-4 and NFS risk estimates for cardiovascular events were not influenced by concomitant NAFLD. REGISTRATION: URL: http://www.crd.york.ac.uk/prospero/ PROSPERO (registration number: CRD42023421092). GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-23883-x.