中国中老年人肝脏生物标志物与死亡风险的前瞻性关联研究  

Prospective association between liver biomarkers and mortality risk in Chinese middle-aged and elderly populations

作　　者：宋树摇 巫婷 余灿清[1,2,3] 孙点剑一 裴培 杜怀东 陈君石[5] 陈铮鸣 吕筠[1,2,3,6] 李立明[1,2,3] 庞元捷[1,2,3] 中国慢性病前瞻性研究项目协作组[7] Song Shuyao;Wu Ting;Yu Canqing;Sun Dianjianyi;Pei Pei;Du Huaidong;Chen Junshi;Chen Zhengming;Lyu Jun;Li Liming;Pang Yuanjie;the China Kadoorie BiobankCollaborative Group(Department of Epidemiology and Biostatistics,School of Public Health,Peking University,Beijing 100191,China;Peking University Center for Public Health and Epidemic Preparedness&Response,Beijing 100191,China;Key Laboratory of Epidemiology of Major Diseases(Peking University),Ministry of Education,Beijing 100191,China;Clinical Trial Service Unit and Epidemiological Studies Unit,Nuffield Department of Population Health,University of Oxford,Oxford OX37LF,United Kingdom;China National Center for Food Safety Risk Assessment,Beijing 100022,China;State Key Laboratory of Vascular Homeostasis and Remodeling,Peking University,Beijing 100191,China;不详)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]北京大学公众健康与重大疫情防控战略研究中心,北京100191 [3]重大疾病流行病学教育部重点实验室(北京大学),北京100191 [4]牛津大学临床与流行病学研究中心纳菲尔德人群健康系,牛津OX37LF [5]国家食品安全风险评估中心,北京100022 [6]北京大学血管稳态与重构全国重点实验室,北京100191 [7]不详

出　　处：《中华流行病学杂志》2025年第4期549-556,共8页Chinese Journal of Epidemiology

基　　金：国家重点研发计划(2023YFC3606300);国家自然科学基金(82304223,82192901,82192904,82192900)。

摘　　要：目的分析中国中老年人群中肝脏生物标志物与死亡风险的前瞻性关联,评估肝脏生物标志物对死亡风险预测的价值。方法在中国慢性病前瞻性研究第三次重复调查数据合格的22758名研究对象中,采用Cox比例风险回归模型分析5个肝脏生物标志物与死亡的前瞻性关联。5个肝脏生物标志物包括2个肝脏影像标志物(肝脏脂肪衰减参数和肝脏硬度值)和3个血清肝酶标志物[谷氨酰转肽酶(GGT)、ALT和AST]。应用限制性立方样条分析肝脏生物标志物与死亡的非线性关联。采用受试者工作特征曲线下面积(AUC)评估肝脏生物标志物对死亡的预测能力。结果研究对象年龄(65.2±9.1)岁,中位随访时间1.5年,共发生307名研究对象死亡。与无肝脂肪变性人群相比,重度肝脂肪变性人群死亡风险增加79%,HR值(95%CI)为1.79(1.06~3.03)。与无肝纤维化人群相比,进展期肝纤维化和肝硬化人群死亡风险分别增加48%和91%(均P<0.05)。GGT每增加1个标准差,死亡风险增加10%(HR=1.10,95%CI:1.05~1.15),且GGT与死亡风险的正向关联在较高水平趋于平缓。AST与死亡风险呈U形关联。在传统模型中加入肝脏生物标志物后,AUC为0.718(95%CI:0.679~0.757),较传统模型升高0.030(P<0.001)。结论重度肝脂肪变性、肝纤维化程度升高和GGT水平升高与死亡风险增加相关,AST与死亡风险具有U形关联。肝脏生物标志物能提升传统模型对全因死亡的预测能力。Objective To analyze the prospective associations between liver biomarkers and mortality among Chinese middle-aged and elderly populations and to evaluate the mortality risk predictive value.Methods A total of 22758 participants from the 3rd resurvey of the China Kadoorie Biobank were included.Cox proportional hazard models were used to analyze the prospective associations of 5 liver biomarkers with mortality.These liver biomarkers included two liver imaging biomarkers(liver fat attenuation parameter,liver stiffness measurement)and three serum liver enzyme biomarkers[gamma-glutamyl transferase(GGT),ALT,and AST].Restricted cubic spline was used to assess the nonlinear associations between biomarkers and mortality.The area used the receiver operating characteristic curve(AUC)to evaluate the predictive ability of the models after incorporating liver biomarkers into traditional prediction models for mortality.Results The mean age of the participants was(65.2±9.1)years,with a median follow-up of 1.5 years,during which 307 deaths occurred.Compared to individuals without hepatic steatosis,those with severe hepatic steatosis had a 79% higher risk of mortality,with a HR of 1.79(95%CI:1.06-3.03).Compared to individuals without hepatic fibrosis,those with advanced fibrosis and cirrhosis had higher mortality risks of 48% and 91%,respectively(both P<0.05).For each standard deviation increase in GGT,the mortality risk increased by 10%(HR=1.10,95%CI:1.05-1.15),with the positive association plateauing at higher GGT levels.AST exhibited a U-shaped association with mortality risk.The AUC of the prediction model adding liver biomarkers into traditional prediction factors was 0.718(95%CI:0.679-0.757),with an increase of 0.030(P<0.001)compared with the traditional model.Conclusions Severe hepatic steatosis,higher levels of hepatic fibrosis,and elevated GGT levels are significantly associated with higher mortality risk.AST shows a U-shaped nonlinear association with mortality risk.Incorporating liver biomarkers into traditional risk

关 键 词：肝脏生物标志物 死亡风险 前瞻性研究 

分 类 号：R575[医药卫生—消化系统]