Fan Hong, Zhang Pengyan, Liu Zhenqiu, Zhao Renjia, Suo Chen, Chen Xingdong, Zhang Tiejun
Department of Epidemiology, School of Public Health, Fudan University, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China.
Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China.
J Clin Transl Hepatol. 2023 Jun 28;11(3):525-533. doi: 10.14218/JCTH.2022.00214. Epub 2023 Jan 4.
Metabolic dysfunction and obesity commonly coexist with both alcoholic and nonalcoholic fatty liver disease (AFLD and NAFLD). The association of AFLD and NAFLD with incident diseases in individuals with different metabolic phenotypes are unclear.
UK Biobank study participants were screened for the presence of fatty liver at baseline. Body mass index and metabolic dysfunction were used to define metabolic phenotypes. Cox regression model was performed to examine the associations of AFLD and NAFLD with incident significant liver diseases (SLDs), cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and cancers, respectively.
A total of 43,974 AFLD and 103,248 NAFLD cases were identified. Both AFLD and NAFLD were associated with an increased risk of diseases of interest. The effects were amplified by obesity and metabolic abnormalities and modified by metabolic phenotypes. Compared to individuals free of fatty liver and with phenotype of metabolically healthy-normal weight, AFLD [hazard ratio (HR) 3.27; 95% CI: 1.95-5.47)] and NAFLD (HR 2.25; 95% CI: 1.28-3.94) cases with phenotype of metabolically obese-normal weight had the greatest risk of SLDs. For CVDs, CKDs, and cancer, the greatest risks were detected in AFLD and NAFLD cases with phenotype of metabolically obese-overweight/obesity. In this subpopulation, AFLD and NAFLD conferred a 2.75-fold (95% CI: 2.32-3.25) and 4.02-fold 95% CI: (3.64-4.43) increased risk of CVDs, 4.37-fold 95% CI: (3.38-5.64) and 6.55-fold 95% CI: (5.73-7.48) increased risk of CKDs, and 1.19-fold 95% CI: (1.08-1.27) and 1.21-fold 95% CI: (1.14-1.28) increased risk of cancers, respectively.
Metabolic phenotypes modified the association of AFLD and NAFLD with intrahepatic and extrahepatic diseases.
代谢功能障碍和肥胖通常与酒精性和非酒精性脂肪性肝病（AFLD和NAFLD）并存。AFLD和NAFLD与不同代谢表型个体的新发疾病之间的关联尚不清楚。
对英国生物银行研究参与者在基线时进行脂肪肝筛查。采用体重指数和代谢功能障碍来定义代谢表型。分别进行Cox回归模型分析，以检验AFLD和NAFLD与新发严重肝脏疾病（SLD）、心血管疾病（CVD）、慢性肾脏疾病（CKD）和癌症之间的关联。
共识别出43974例AFLD病例和103248例NAFLD病例。AFLD和NAFLD均与所关注疾病的风险增加相关。肥胖和代谢异常会放大这种影响，且受代谢表型的影响。与无脂肪肝且代谢健康-正常体重表型的个体相比，代谢性肥胖-正常体重表型的AFLD病例[风险比（HR）3.27；95%置信区间：1.95 - 5.47]和NAFLD病例（HR 2.25；95%置信区间：1.28 - 3.94）发生SLD的风险最高。对于CVD、CKD和癌症，在代谢性肥胖-超重/肥胖表型的AFLD和NAFLD病例中检测到的风险最高。在该亚组中，AFLD和NAFLD使CVD风险分别增加2.75倍（95%置信区间：2.32 - 3.25）和4.02倍（95%置信区间：3.64 - 4.43），使CKD风险分别增加4.37倍（95%置信区间：3.38 - 5.64）和6.55倍（95%置信区间：5.73 - 7.48），使癌症风险分别增加1.19倍（95%置信区间：1.08 - 1.27）和1.21倍（95%置信区间：1.14 - 1.28）。
代谢表型改变了AFLD和NAFLD与肝内和肝外疾病之间的关联。
