Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK.
Leicester Real World Evidence Unit, Leicester General Hospital, Leicester, UK.
Liver Int. 2019 Mar;39(3):557-567. doi: 10.1111/liv.13994. Epub 2018 Dec 4.
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.
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.
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.
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.
非酒精性脂肪性肝病（NAFLD）与心血管疾病（CVD）和 2 型糖尿病（T2DM）之间的因果关系仍未得到证实。我们旨在通过检查观察性关联对可能混杂因素的敏感性来定量因果关系的可能性。
于 2018 年 6 月 5 日检索了研究 NAFLD 与 CVD 或 T2DM 纵向关联的研究。采用随机效应荟萃分析合并研究特异性相对风险（RR），并使用偏倚分析中的汇总估计值。
13 项（258743/18383 例患者/事件）和 20 项（240251/12891 例患者）研究报道了 NAFLD 与 CVD 和 T2DM 的相关性。与无 NAFLD 的患者相比，NAFLD 患者的合并 RR 分别为 CVD 1.48（95%CI：0.96，2.29）和 T2DM 2.17（1.77，2.65）。在偏倚分析中，对于与 NAFLD 和 CVD 均相关且 RR 为 1.25 的未测量混杂因素，具有真实（因果）效应的 NAFLD 对 CVD 的 RR 超过 1.10（即 NAFLD 患者 CVD 风险增加 10%）的研究比例为 0.67（95%CI：0.42，0.92），而对于增加 75%，该比例为 0.36（0.11，0.62）。对于 T2DM，NAFLD 患者的 T2DM 风险增加 10%时，RR 为 0.97（0.91，1.00），而增加 75%时，RR 为 0.70（0.49，0.92）。
本研究结果强烈提示 NAFLD 与 T2DM 之间存在因果关系，而 NAFLD 与 CVD 之间因果关系的证据则不太可靠。针对 NAFLD 的治疗策略可能会降低发生 T2DM 的风险。
