Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD

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 scor...

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Main Authors: Jun Zhang, Lin Li, Ling Lin, Yifan Wu, Lifen Hu, Zhaolan Feng, Deju Zhang, Taoli Fu, Huilei Zhao, Xiaoping Yin, Peng Yu, Xiang Gu, Xiao Liu, Wenting Wang
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Language:English
Published: BMC 2025-08-01
Series:BMC Public Health
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Online Access:https://doi.org/10.1186/s12889-025-23883-x
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author Jun Zhang
Lin Li
Ling Lin
Yifan Wu
Lifen Hu
Zhaolan Feng
Deju Zhang
Taoli Fu
Huilei Zhao
Xiaoping Yin
Peng Yu
Xiang Gu
Xiao Liu
Wenting Wang
author_facet Jun Zhang
Lin Li
Ling Lin
Yifan Wu
Lifen Hu
Zhaolan Feng
Deju Zhang
Taoli Fu
Huilei Zhao
Xiaoping Yin
Peng Yu
Xiang Gu
Xiao Liu
Wenting Wang
author_sort Jun Zhang
collection DOAJ
description 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
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spelling doaj-art-1f180bdc7b0e4e13bc78fc237061c1b92025-08-20T04:02:50ZengBMCBMC Public Health1471-24582025-08-0125111710.1186/s12889-025-23883-xPrognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLDJun Zhang0Lin Li1Ling Lin2Yifan Wu3Lifen Hu4Zhaolan Feng5Deju Zhang6Taoli Fu7Huilei Zhao8Xiaoping Yin9Peng Yu10Xiang Gu11Xiao Liu12Wenting Wang13Department of Cardiology, Affiliated Hospital of Jiujiang UniversityDepartment of Traditional Chinese Medicine, Fujian University of Traditional Chinese MedicineFujian Medical UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital of Nanchang UniversityDepartment of Infectious Diseases, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Cardiovascular Medicine, Jiu jiang NO.1 People’s HospitalFood and Nutritional Sciences, School of Biological Sciences, The University of Hong KongDepartment of Endocrinology and Metabolism, The Third Hospital of NanchangDepartment of Anesthesiology, The Third Hospital of NanchangDepartment of Neurology, Affiliated Hospital of Jiujiang UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, Affiliated Hospital of Jiujiang UniversityJiujiang Clinical Precision Medicine Research CenterDepartment of Anesthesiology, The Second Affiliated Hospital of Hainan Medical UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12889-025-23883-xNonalcoholic fatty liver diseaseCardiovascular diseaseCardiovascular mortalityMeta-analysis
spellingShingle Jun Zhang
Lin Li
Ling Lin
Yifan Wu
Lifen Hu
Zhaolan Feng
Deju Zhang
Taoli Fu
Huilei Zhao
Xiaoping Yin
Peng Yu
Xiang Gu
Xiao Liu
Wenting Wang
Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD
BMC Public Health
Nonalcoholic fatty liver disease
Cardiovascular disease
Cardiovascular mortality
Meta-analysis
title Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD
title_full Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD
title_fullStr Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD
title_full_unstemmed Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD
title_short Prognostic value of FIB-4 and NFS for cardiovascular events in patients with and without NAFLD
title_sort prognostic value of fib 4 and nfs for cardiovascular events in patients with and without nafld
topic Nonalcoholic fatty liver disease
Cardiovascular disease
Cardiovascular mortality
Meta-analysis
url https://doi.org/10.1186/s12889-025-23883-x
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