超米兰标准肝细胞癌肝移植术后复发预测模型的建立

Development of a new model for predicting recurrence after liver transplantation for hepatocellular carcinoma beyond Milan criteria

目的根据患者术前和术后相关指标建立一个预测超米兰标准肝细胞癌(HCC)患者肝移植术后复发的模型。方法回顾性分析2014年8月—2018年7月在天津市第一中心医院接受首次原位肝移植的超米兰标准HCC患者的临床资料。根据随访期间肿瘤是否复发,将患者分为复发组和未复发组。计量资料组间比较采用t检验或Mann-Whitney U检验,计数资料组间比较使用χ^(2)检验或Fisher精确检验。生存曲线采用Kaplan-Meier法构建,曲线间差异采用log-rank检验。使用单因素和多因素Cox比例风险回归筛选影响术后无复发生存的危险因素。根据筛选得出的危险因素建立预测超米兰标准HCC患者肝移植术后复发的模型,使用受试者工作特征曲线(ROC曲线)下面积来判断预测效能,Hosmer-Lemeshow检验用于评估模型的拟合优度。结果共纳入117例超米兰标准HCC患者,中位随访时间24(1~74)个月。共53例(45.3%)患者术后复发,其中52例(98.1%)于术后3年内复发,中位复发时间为6(1~52)个月。Cox风险回归分析显示患者术前血清甲胎蛋白(AFP)>769 ng/mL,中性粒细胞与淋巴细胞比值(NLR)>3.75以及ki67指数>0.25是患者肝移植术后无复发生存的独立危险因素(P值均<0.05)。根据这3个危险因素建立的评分模型ROC曲线下面积为0.843,并且具有良好的灵敏度(88.7%)及特异度(70.3%)。根据约登指数最大化标准选取最佳截断值,将患者分为低危组(0~1分)和高危组(1.5~4分),log-rank检验显示低危组患者术后3年、5年无复发生存率(84.1%、72.0%)明显高于高危组(10.9%、10.9%)(χ^(2)=29.425,P<0.001)。结论超米兰标准肝癌肝移植要慎重进行,本研究根据患者术前AFP、NLR以及ki67指数建立的预测模型有助于更精准地把握此类患者的肝移植指征。

Objective To develop a new model for predicting recurrence after liver transplantation for hepatocellular carcinoma(HCC)beyond Milan criteria based on related preoperative and postoperative indicators.Methods A retrospective analysis was performed for the clinical data of the patients with HCC beyond Milan criteria who underwent orthotopic liver transplantation for the first time in Tianjin First Central Hospital from August 2014 to July 2018,and according to the presence or absence of recurrence during follow-up,the patients were divided into recurrence group and no-recurrence group.The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to identify the risk factors for recurrence-free survival after surgery.A new model was developed for recurrence after liver transplantation in the patients with HCC beyond Milan criteria based on the risk factors identified.The area under the receiver operating characteristic curve(AUC)was used to evaluate predictive performance,and the Hosmer-Lemeshow test was used to assess the goodness of fit of the model.Results A total of 117 patients with HCC beyond Milan criteria were enrolled in this study,with a median follow-up time of 24(1-74)months.A total of 53 patients(45.3%)experienced recurrence after surgery,among whom 52(98.1%)had recurrence within 3 years after surgery,with a median time to recurrence of 6(1-52)months.The Cox proportional hazards regression analysis showed that preoperative serum alpha-fetoprotein(AFP)>769 ng/mL,neutrophil-lymphocyte ratio(NLR)>3.75,and ki67 index>0.25 were independent risk factors for recurrence-free survival after liver transplantation.The model established based on these three risk factors had an AUC of 0.843,with good sensitivity(88.7%)and specificity(70.3%).The optimal cut-off value was selected according to the maximization of Youden index,and then the patients were divided into low-risk group(0-1 point)and high-risk group(1.5-4 points).The log-rank test showed that the low-risk group had significantly higher 3-and 5-year recurrence-free survival rates than the high-risk group(84.1%/72.0%vs 10.9%/10.9%,χ^(2)=29.425,P<0.001).Conclusion Liver transplantation for HCC beyond Milan criteria should be performed with caution,and the predictive model established based on preoperative AFP,NLR,and ki67 index can accurately assess the indication for liver transplantation in such patients.