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Causality between non‐alcoholic fatty liver disease and risk of cardiovascular disease and type 2 diabetes: A meta‐analysis with bias analysis
Author(s) -
Morrison Amy E.,
Zaccardi Francesco,
Khunti Kamlesh,
Davies Melanie J.
Publication year - 2019
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13994
Subject(s) - confounding , medicine , fatty liver , meta analysis , relative risk , disease , type 2 diabetes , type 2 diabetes mellitus , causality (physics) , diabetes mellitus , observational study , metabolic syndrome , publication bias , gastroenterology , confidence interval , obesity , endocrinology , physics , quantum mechanics
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.