Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton, UK.
Metabolism. 2018 Oct;87:1-12. doi: 10.1016/j.metabol.2018.06.004. Epub 2018 Jun 20.
It is currently uncertain whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of colorectal tumours. We performed a meta-analysis of relevant observational studies to quantify the magnitude of the association between NAFLD and risk of colorectal adenomas and cancer.
We searched PubMed, Scopus and Web of Science from January 2000 to November 2017 using pre-defined keywords to identify observational studies of asymptomatic adults undergoing screening colonoscopy, in which NAFLD was diagnosed by imaging or histology. Data from selected studies were extracted and meta-analysis was performed using random-effects modelling.
Eleven observational studies (8 cross-sectional and 3 longitudinal) with aggregate data on 91,124 asymptomatic adults (32.1% with NAFLD) of predominantly Asian descent accounting for a total of 14,911 colorectal adenomas and 1684 cancers were included in the final analysis. NAFLD was associated with an increased risk of prevalent colorectal adenomas (n = 7 studies using liver imaging techniques; random-effects odds ratio [OR] 1.28, 95% CI 1.11-1.48; I = 82.9% or n = 1 study using liver biopsy; random-effects OR 1.61, 95% CI 0.90-2.89) and cancer (n = 4 studies using liver imaging techniques; random-effects OR 1.56, 95% CI 1.25-1.94; I = 65.6% or n = 1 study using liver biopsy; random-effects OR 3.04, 95% CI 1.29-7.18). NAFLD was also associated with an increased risk of incident colorectal adenomas (n = 3 studies; random-effects hazard ratio [HR] 1.42, 95% CI 1.18-1.72; I = 0%) and cancer (n = 1 study; random-effects HR 3.08, 95% CI 1.02-9.03). These risks were independent of age, sex, smoking, body mass index and diabetes (or metabolic syndrome). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias.
This meta-analysis of observational studies (involving asymptomatic individuals of predominantly Asian descent undergoing screening colonoscopy) suggests that NAFLD (detected by imaging or biopsy) is independently associated with a moderately increased prevalence and incidence of colorectal adenomas and cancer. However, the observational design of the studies does not allow for proving causality, and the possibility of residual confounding by some unmeasured factors cannot be ruled out. More prospective studies, particularly in European and American individuals, and mechanistic studies are required to better understand the association between NAFLD and colonic carcinogenesis.
目前尚不确定非酒精性脂肪性肝病(NAFLD)是否会增加结直肠肿瘤的风险。我们进行了一项荟萃分析,以量化 NAFLD 与结直肠腺瘤和癌症风险之间的关联程度。
我们使用预定义的关键字从 2000 年 1 月至 2017 年 11 月在 PubMed、Scopus 和 Web of Science 上进行了检索,以识别接受筛查性结肠镜检查的无症状成年人的观察性研究,其中 NAFLD 通过影像学或组织学诊断。从选定的研究中提取数据,并使用随机效应模型进行荟萃分析。
最终分析纳入了 11 项观察性研究(8 项横断面研究和 3 项纵向研究),共有 91124 名无症状成年人(32.1%患有 NAFLD)的数据,主要来自亚洲,共发生 14911 例结直肠腺瘤和 1684 例癌症。NAFLD 与结直肠腺瘤的患病率增加相关(使用肝脏成像技术的 7 项研究;随机效应比值比 [OR] 1.28,95%CI 1.11-1.48;I²=82.9%或使用肝脏活检的 1 项研究;随机效应 OR 1.61,95%CI 0.90-2.89)和癌症(使用肝脏成像技术的 4 项研究;随机效应 OR 1.56,95%CI 1.25-1.94;I²=65.6%或使用肝脏活检的 1 项研究;随机效应 OR 3.04,95%CI 1.29-7.18)。NAFLD 也与结直肠腺瘤的发生率增加相关(使用肝脏成像技术的 3 项研究;随机效应 HR 1.42,95%CI 1.18-1.72;I²=0%或使用肝脏活检的 1 项研究;随机效应 HR 3.08,95%CI 1.02-9.03)。这些风险独立于年龄、性别、吸烟、体重指数和糖尿病(或代谢综合征)。敏感性分析并未改变这些发现。漏斗图和 Egger 检验未发现显著的发表偏倚。
这项对观察性研究(涉及接受筛查性结肠镜检查的主要来自亚洲的无症状个体)的荟萃分析表明,NAFLD(通过影像学或活检检测)与结直肠腺瘤和癌症的患病率和发生率适度增加独立相关。然而,研究的观察性设计不允许证明因果关系,并且不能排除某些未测量因素的残余混杂的可能性。需要更多的前瞻性研究,特别是在欧洲和美洲个体中,以及机制研究,以更好地了解 NAFLD 与结直肠癌变之间的关联。