Wang Wei, Sun Pengfei, Ren Xintian, Lv Tingting, Li Min
Department of Clinical Laboratory, Beijing Friendship Hospital Capital Medical University Beijing China.
Department of Ultrasound, Beijing Friendship Hospital Capital Medical University Beijing China.
Health Sci Rep. 2025 Mar 10;8(3):e70551. doi: 10.1002/hsr2.70551. eCollection 2025 Mar.
Nonalcoholic fatty liver disease (NAFLD) is an escalating global health concern with significant implications for cancers. A better understanding of the causal relationship between NAFLD and extrahepatic cancers might help in clinical management of NAFLD and prevent its adverse outcomes.
This study encompassed two complementary approaches. First, the cross-sectional analysis was performed to examine the association between NAFLD and extrahepatic cancers, utilizing individual-level data from the National Health and Nutrition Examination Survey (2017-March 2020, 2021-2023 cycles). Logistic regression model was utilized to evaluate the association. Subsequently, Mendelian randomization (MR) analysis was conducted to explore the causal association between NAFLD and extrahepatic cancers. Summary-level data for genetically predicted NAFLD and extrahepatic cancers were derived from large-scale genome-wide association studies (GWAS), IEU Open GWAS project and the UK Biobank. The inverse variance weighting (IVW) method with a random-effect model was utilized as the main analysis.
A total of 10,010 participants were included in the cross-sectional analysis. No association was observed between NAFLD and extrahepatic cancers after adjusting for potential confounders, with odd ratios (ORs) ranging from 0.872 to 2.171. IVW MR analysis showed genetic liability to genetically predicted cALT and imaging-and-biopsy confirmed NAFLD were not causally associated with extrahepatic cancers, with ORs ranging from 0.957 to 1.118 (all > 0.050). Moreover, genetically predicted cALT and imaging-and-biopsy confirmed NAFLD were causally associated with liver & bile duct cancer (OR = 1.001, 95% CI = 1.000-1.001, = 0.011; OR = 1.001, 95% CI = 1.000-1.001, < 0.001), reinforcing a well-documented link between NAFLD and liver & bile duct cancer.
Our findings demonstrated that NAFLD was not causally associated with common extrahepatic cancers. Further research is required to validate these results from a mechanistic perspective.
非酒精性脂肪性肝病（NAFLD）是一个日益严重的全球健康问题，对癌症有重大影响。更好地理解NAFLD与肝外癌症之间的因果关系可能有助于NAFLD的临床管理并预防其不良后果。
本研究采用了两种互补的方法。首先，进行横断面分析，利用国家健康与营养检查调查（2017年 - 2020年3月、2021年 - 2023年周期）的个体水平数据，来检验NAFLD与肝外癌症之间的关联。使用逻辑回归模型评估该关联。随后，进行孟德尔随机化（MR）分析，以探索NAFLD与肝外癌症之间的因果关联。基因预测的NAFLD和肝外癌症的汇总水平数据来自大规模全基因组关联研究（GWAS）、IEU开放GWAS项目和英国生物银行。采用随机效应模型的逆方差加权（IVW）方法作为主要分析方法。
横断面分析共纳入10,010名参与者。在调整潜在混杂因素后，未观察到NAFLD与肝外癌症之间存在关联，比值比（OR）范围为0.872至2.171。IVW MR分析显示，基因预测的cALT和影像学及活检确诊的NAFLD的遗传易感性与肝外癌症无因果关联，OR范围为0.957至1.118（均>0.050）。此外，基因预测的cALT和影像学及活检确诊的NAFLD与肝癌和胆管癌有因果关联（OR = 1.001，95%CI = 1.000 - 1.001，P = 0.011；OR = 1.001，95%CI = 1.000 - 1.001，P < 0.001），强化了NAFLD与肝癌和胆管癌之间已充分记录的联系。
我们的研究结果表明，NAFLD与常见的肝外癌症无因果关联。需要进一步研究从机制角度验证这些结果。
