基于up-to-seven标准肝细胞癌肝移植术后生存预测模型的建立和验证  

Modeling and validation of a survival prediction model for hepatocellular carcinoma patients after liver transplantation based on up-to-seven criteria

作　　者：董骏峰 滕飞[1] 李培磊[1] 孙克彦[1] 傅宏[1] 郭闻渊[1] 丁国善[1] DONG Jun-feng;TENG Fei;LI Pei-lei;SUN Ke-yan;FU Hong;GUO Wen-yuan;DING Guo-shan(Department of Organ Transplantation,Changzheng Hospital,Navy Medical University（Second Military Medical University）,Shanghai 200003,Chin)

机构地区：[1]海军军医大学(第二军医大学)长征医院器官移植科,上海200003

出　　处：《第二军医大学学报》2018年第7期745-752,共8页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(81671576);上海市卫生和计划生育委员会项目(201640274)~~

摘　　要：目的建立并验证基于up-to-seven(Up7)标准肝细胞癌(HCC)肝移植术后患者的长期生存Cox回归预测模型,以辅助制定临床决策。方法回顾性分析251例符合Up7标准的HCC肝移植术后患者的临床和随访资料。采用逐步回归向前法进行多因素Cox回归分析,获得HCC肝移植术后患者长期生存的独立预测因素,并建立长期生存Cox回归预测模型。使用R 3.4.3软件获得预测模型评分,采用生存决策树方式确定模型的截断值。绘制预测模型在其他肝移植标准[上海复旦标准、加利福尼亚大学旧金山分校(UCSF)标准、意大利米兰(Milan)标准]下HCC肝移植术后患者的Kaplan-Meier生存曲线,并采用log-rank检验分析组间差异。采用受试者工作特征(ROC)曲线检验预测模型的预测效能。结果多因素Cox回归分析显示,甲胎蛋白(AFP)、总胆红素(T-Bil)、微血管侵犯(MVI)、肿瘤最大径(Diameter)是HCC肝移植术后患者长期生存的独立预测因素,据此建立的长期生存Cox回归预测模型命名为ATMD(AFP,T-Bil,MVI,Diameter)模型:h(t,x)=h0(t)exp[0.284×肿瘤最大径(cm)+0.773×MVI(是=1;否=0)+0.404×lg AFP(ng/m L)+0.003×T-Bil(μmol/L)],根据判别生存树设定ATMD模型截断值为1.44,评分>1.44为高危组,≤1.44为低危组。符合Up7标准的高危组和低危组患者分别为87例和164例,符合上海复旦标准的分别为33例和144例,符合UCSF标准的分别为29例和134例,符合Milan标准的分别为29例和131例。Kaplan-Meier生存曲线分析显示,在Up7标准、上海复旦标准、UCSF标准和Milan标准下ATMD模型高危组和低危组患者累积生存率差异均有统计学意义(P<0.001,P=0.008,P<0.001,P=0.001),ATMD模型预测的HCC肝移植术后3年生存的ROC曲线下面积分别是76.63%、75.87%、73.32%和69.41%。结论 ATMD模型对于符合Up7标准、上海复旦标准、UCSF标准和Milan标准的HCC肝移植术后生存情况有良好的预测能力,对符合以上标准的HCC肝移植患者的Objective To establish a long-term survival prediction model for hepatocellular carcinoma（HCC） patients after liver transplantation based on up-to-seven（Up7） criteria, and to validate the prediction model in different liver transplantation criteria, so as to assist clinical decision-making for the treatment of HCC. Methods We retrospectively analyzed the clinical and follow-up data of 251 HCC patients who underwent liver transplantation with Up7 criteria. Stepwise regression method was used to conduct multivariate Cox regression analysis to obtain the independent predictors of long-term survival after HCC liver transplantation, and to establish the survival Cox regression prediction model. R 3.4.3 software was used to score the prediction model, and the decision tree technique was used to determine the cut-off value. The Kaplan-Meier survival curve of the HCC patients after liver transplantation was drawn to validate the prediction model in different criteria（Shanghai Fudan criteria, University of California, San Francisco [UCSF] criteria and Italy Milan criteria）, and the difference between groups was analyzed by log-rank test. The receiver operating characteristic（ROC） curve was used to test the predictive effectiveness of the model. Results Multivariate Cox regression analysis suggested that α-fetoprotein（AFP）, total bilirubin（T-Bil）, microvascular invasion（MVI） and tumor maximal diameter（Diameter） were the independent predictors of long-term survival of HCC liver transplant recipients after liver transplantion. We built the ATMD（AFP, T-Bil, MVI, Diameter） model using these factors： h（t, x）=h0（t） exp（0.284×Diameter [cm]＋0.773×MVI [yes=1; no=0]＋0.404×lg AFP [ng/m L]＋0.003×T-Bil [μmol/L]）. The cut-off value of ATMD model was 1.44. The scores being more than 1.44 were defined as the high-risk group, and scores being 1.44 or less were defined as the low-risk group. The cases in the high-risk and low-risk groups who met the Up7 criteria, Shanghai Fudan c

关 键 词：ATMD模型 肝肿瘤 肝细胞癌 肝移植 长期生存 预后 

分 类 号：R735.7[医药卫生—肿瘤]