Causality between non-alcoholic fatty liver disease and risk of cardiovascular disease and type 2 diabetes: a meta-analysis with bias analysis
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BACKGROUND & AIMS: A causal association of non-alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and type 2 diabetes (T2DM) remains unproved. We aimed to quantify the likelihood of causality examining the sensitivity of observational associations to possible confounding. METHODS: Studies investigating longitudinal associations of NAFLD with CVD or T2DM were searched on 5 June 2018. Study-specific relative risks (RRs) were combined in random-effects meta-analyses and pooled estimates used in bias analyses. RESULTS: Associations of NAFLD with CVD and T2DM were reported in 13 (258 743/18 383 participants/events) and 20 (240 251/12 891) studies respectively. Comparing patients with NAFLD to those without, the pooled RR was 1.48 (95% CI: 0.96, 2.29) for CVD and 2.17 (1.77, 2.65) for T2DM. In bias analyses, for an unmeasured confounder associated to both NAFLD and CVD with a RR of 1.25, the proportion of studies with a true (causal) effect of NAFLD on CVD surpassing a RR of 1.10 (ie, 10% increased risk of CVD in participants with NAFLD) was 0.67 (95% CI: 0.42, 0.92) while for 75% increase, it was 0.36 (0.11, 0.62). Corresponding figures for T2DM were 0.97 (0.91, 1.00) for a 10% increased risk of T2DM in participants with NAFLD to 0.70 (0.49, 0.92) for a 75% increase. CONCLUSIONS: The results of this study are strongly suggestive for a causal relationship between NAFLD and T2DM, while the evidence for a causal link between NAFLD and CVD is less robust. Therapeutic strategies targeting NAFLD are likely to reduce the risk of developing T2DM.
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NAFLD is the most common chronic liver disease worldwide and a risk factor for type 2 diabetes, obesity, and cardiovascular disease.
“NAFLD is the most common chronic liver disease worldwide and a risk factor for type 2 diabetes, obesity, and cardiovascular disease (CVD) [8,12,22].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [22]
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- Authors
- Morrison, A. E., Zaccardi, F., Khunti, K., & Davies, M. J.
- Affiliations
- Leicester General Hospital (GB)
- Corresponding author
- Zaccardi, Francesco
- Venue
- Liver International
- Publisher
- Wiley
- Published
- 2018-12-04
- Volume
- 39
- Issue
- 3
- Pages
- 557-567
- ISSN
- 0106-9543 (ISSN-L)
- 1478-3223
- 1478-3231
- OpenAlex
- W2898460805
- Cited by
- 92
- References
- 45
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 14 · 2023: 13 · 2022: 16 · 2021: 8 · 2020: 14 · 2019: 10 · 2018: 1
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion, other-oa)
- Funders
- National Institute for Health Research
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, cardiovascular disease, type 2 diabetes, causal inference, confounding, bias assessment, relative risk, observational studies
- MeSH terms
- Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Risk Factors, Incidence, Risk Assessment, Non-alcoholic Fatty Liver Disease
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