Mantovani Alessandro, Petracca Graziana, Beatrice Giorgia, Csermely Alessandro, Tilg Herbert, Byrne Christopher D, Targher Giovanni
Endocrinology and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
Gastroenterology, Hepatology, Endocrinology and Metabolism, Department of Internal Medicine I, Medizinische Universität Innsbruck, Innsbruck, Austria.
Gut. 2022 Apr;71(4):778-788. doi: 10.1136/gutjnl-2021-324191. Epub 2021 Mar 8.
We performed a meta-analysis of observational studies to quantify the magnitude of the association between non-alcoholic fatty liver disease (NAFLD) and risk of extrahepatic cancers.
We systematically searched PubMed, Scopus and Web of Science databases from the inception date to 30 December 2020 using predefined keywords to identify observational cohort studies conducted in individuals, in which NAFLD was diagnosed by imaging techniques or International Classification of Diseases codes. No studies with biopsy-proven NAFLD were available for the analysis. Meta-analysis was performed using random-effects modelling.
We included 10 cohort studies with 182 202 middle-aged individuals (24.8% with NAFLD) and 8485 incident cases of extrahepatic cancers at different sites over a median follow-up of 5.8 years. NAFLD was significantly associated with a nearly 1.5-fold to twofold increased risk of developing GI cancers (oesophagus, stomach, pancreas or colorectal cancers). Furthermore, NAFLD was associated with an approximately 1.2-fold to 1.5-fold increased risk of developing lung, breast, gynaecological or urinary system cancers. All risks were independent of age, sex, smoking, obesity, diabetes or other potential confounders. The overall heterogeneity for most of the primary pooled analyses was relatively low. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias.
This large meta-analysis suggests that NAFLD is associated with a moderately increased long-term risk of developing extrahepatic cancers over a median of nearly 6 years (especially GI cancers, breast cancer and gynaecological cancers). Further research is required to decipher the complex link between NAFLD and cancer development.
我们对观察性研究进行了荟萃分析，以量化非酒精性脂肪性肝病（NAFLD）与肝外癌症风险之间关联的程度。
我们使用预定义关键词，系统检索了从起始日期至2020年12月30日的PubMed、Scopus和科学网数据库，以识别针对个体开展的观察性队列研究，其中NAFLD通过影像学技术或国际疾病分类编码进行诊断。没有活检证实为NAFLD的研究可用于分析。使用随机效应模型进行荟萃分析。
我们纳入了10项队列研究，共182202名中年个体（24.8%患有NAFLD），在中位随访5.8年期间有8485例不同部位的肝外癌症发病病例。NAFLD与患胃肠道癌症（食管癌、胃癌、胰腺癌或结直肠癌）风险增加近1.5倍至2倍显著相关。此外，NAFLD与患肺癌、乳腺癌、妇科癌症或泌尿系统癌症风险增加约1.2倍至1.5倍相关。所有风险均独立于年龄、性别、吸烟、肥胖、糖尿病或其他潜在混杂因素。大多数主要汇总分析的总体异质性相对较低。敏感性分析未改变这些结果。漏斗图未显示任何显著的发表偏倚。
这项大型荟萃分析表明，NAFLD与在近6年中位时间内发生肝外癌症的长期风险适度增加相关（尤其是胃肠道癌症、乳腺癌和妇科癌症）。需要进一步研究来解读NAFLD与癌症发生之间的复杂联系。
