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脂肪变性供肝用于肝癌肝移植的预后及影响因素多中心研究 被引量:6

Prognosis and influencing factors of liver transplantation for hepatocellular carcinoma using steatotic donor liver:a multicenter study
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摘要 目的探讨脂肪变性供肝用于肝癌肝移植的预后及影响因素。方法采用回顾性队列研究方法。收集2015年1月至2019年12月2家医学中心收治的152对[树兰(杭州)医院89对、浙江大学医学院附属第一医院63对]脂肪变性供肝用于肝癌肝移植供者和受者的临床病理资料;152例供者, 男131例, 女21例;年龄为(48±12)岁, 供肝轻度脂肪变性130例、中度脂肪变性22例。152例受者, 男138例, 女14例;年龄为(52±9)岁。观察指标:(1)受者随访、总生存和肿瘤无复发生存情况。(2)受者总生存和肿瘤无复发生存影响因素分析。(3)受者总生存和肿瘤无复发生存列线图预测模型构建及评价。采用门诊和电话方式进行随访, 了解受者生存和肿瘤复发情况。随访时间截至2020年12月。正态分布的计量资料以x±s表示, 偏态分布的计量资料以M(IQR)表示。计数资料以绝对数表示。采用Kaplan-Meier法计算生存率和绘制生存曲线, 采用Log-Rank检验进行生存分析。单因素及多因素分析采用COX回归模型。将独立危险因素引入R 3.6.2软件, 构建列线图预测模型, 绘制受试者工作特征曲线(ROC)并以曲线下面积(AUC)和校准曲线评价模型准确度与区分度。结果 (1)受者随访、总生存和肿瘤无复发生存情况:152例脂肪变性供肝用于肝癌肝移植受者均获得随访, 随访时间为45.8(27.6)个月。随访期间, 152例受者总生存时间为36.5(32.3)个月, 肿瘤无复发生存时间为30.4(34.6)个月, 1、3年总生存率和肿瘤无复发生存率分别为73.4%、55.8%和62.2%、43.4%。(2)受者总生存和肿瘤无复发生存影响因素分析。单因素分析结果显示:供肝冷缺血时间、供肝热缺血时间、移植物受者体重比率(GRWR)、ABO血型相容情况、受者体质量指数(BMI)、受者肿瘤长径、受者肿瘤数目、受者肿瘤分化程度、受者术前甲胎蛋白(AFP)是影响受者总生存的相关因素(风险比=6.26, 1.90, 2.47, 4.08, 0.55, 5.16, 3.62, 5.28, 2.65, 95%可信区间为3.01~13.03, 1.07~3.38, 1.36~4.49, 2.07~8.03, 0.31~0.98, 2.56~10.42, 1.95~6.72, 1.60~17.42, 1.48~5.01, P<0.05)。供肝冷缺血时间、GRWR、ABO血型相容情况、受者肿瘤长径、受者肿瘤数目、受者肿瘤分化程度、受者术前AFP是影响受者肿瘤无复发生存的相关因素(风险比=4.24, 2.53, 4.05, 3.39, 3.10, 5.19, 2.63, 95%可信区间为2.50~7.21, 1.54~4.17, 2.12~7.72, 2.04~5.62, 1.91~5.03, 2.04~13.18, 1.61~4.30, P<0.05)。多因素分析结果显示:供肝冷缺血时间≥8 h、GRWR≥2.5%、受者肿瘤长径≥8 cm、受者术前AFP≥400 μg/L是影响受者总生存的独立危险因素(风险比=4.21, 2.58, 4.10, 2.27, 95%可信区间为1.98~8.96, 1.24~5.35, 1.35~12.43, 1.13~4.56, P<0.05)。供肝冷缺血时间≥8 h、GRWR≥2.5%、受者肿瘤长径≥8 cm、受者肿瘤数目≥3个、受者术前AFP≥400 μg/L是影响受者肿瘤无复发生存的独立危险因素(风险比=3.37, 2.63, 2.42, 2.12, 2.22, 95%可信区间为1.70~6.67, 1.40~4.96, 1.04~5.66, 1.08~4.18, 1.26~3.90, P<0.05)。(3)受者总生存和肿瘤无复发生存列线图预测模型构建及评价。纳入供肝冷缺血时间、GRWR、受者肿瘤长径、受者术前AFP构建受者总生存列线图预测模型;纳入供肝冷缺血时间、GRWR、受者肿瘤长径、受者肿瘤数目、受者术前AFP构建受者肿瘤无复发生存列线图预测模型。ROC显示:受者总生存列线图预测模型AUC=0.84(95%可信区间为0.76~0.92, P<0.05), 诊断最佳临界值为7.3, 特异度、灵敏度分别为87.6%、70.0%。受者肿瘤无复发生存列线图预测模型AUC=0.79(95%可信区间为0.71~0.87, P<0.05), 诊断最佳临界值为5.8, 特异度、灵敏度分别为97.4%、52.5%。校准曲线显示:列线图预测模型对受者总生存和肿瘤无复发生存高危人群具有良好区分度。结论供肝冷缺血时间≥8 h、GRWR≥2.5%、受者肿瘤长径≥8 cm、受者术前AFP≥400 μg/L是影响脂肪变性供肝用于肝癌肝移植受者总生存的独立危险因素;供肝冷缺血时间≥8 h、GRWR≥2.5%、受者肿瘤长径≥8 cm、受者肿瘤数目≥3个、受者术前AFP≥400 μg/L是影响脂肪变性供肝用于肝癌肝移植受者肿瘤无复发生存的独立危险因素。 Objective To investigate the prognosis and influencing factors of liver transplantation(LT)for hepatocellular carcinoma(HCC)using steatotic donor liver.Methods The retrospective cohort study was conducted.The clinicopathological data of 152 pairs of donors and the corresponding recipients undergoing LT for HCC in the two medical centers[89 pairs in Shulan(Hangzhou)Hospital and 63 pairs in the First Affiliated Hospital of Zhejiang University School of Medicine]from January 2015 to December 2019 were collected.Of 152 donors,there were 131 males and 21 females,aged(48±12)years,and there were 130 cases with liver mild steatosis and 22 cases with liver moderate steatosis.Of 152 recipients,there were 138 males and 14 females,aged(52±9)years.Observation indicators:(1)follow-up,overall survival and tumor recurrence free survival of recipients;(2)influencing factors for overall survival and tumor recurrence free survival of recipients;(3)construction and validation of nomogram prediction model for overall survival and tumor recurrence free survival of recipients.Follow-up was conducted using outpatient examination and telephone interview to detect survival and tumor recurrence of recipients up to December 2020.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were represented as M(IQR).Count data were described as absolute numbers.The Kaplan-Meier method was used to calculate the survival time and draw survival curve,and the Log-Rank test was used for survival analysis.The COX regression model was used for univariate and multivariate analysis.The independent risk factors were brought into the R 3.6.2 software to construct nomogram prediction model and draw the receiver operating characteristic(ROC)curve.The accuracy and discrimination of the nomogram prediction model were evaluated using the area under curve(AUC)and the calibration curve.Results(1)Follow-up,overall survival and tumor recurrence free survival of recipients.All the 152 recipients undergoing LT for HCC using steatotic donor liver were followed up for 45.8(27.6)months,with the overall survival time and tumor recurrence free survival time of 36.5(32.3)months and 30.4(34.6)months.The 1-year,3-year overall survival rates and tumor recurrence free rates of the 152 recipients were 73.4%,55.8%and 62.2%,43.4%,respectively.(2)Influencing factors for overall survival and tumor recurrence free survival of recipients.Results of univariate analysis showed that the donor liver cold ischemia time(CIT),the donor liver warm ischemia time(WIT),graft-to-recipient weight ratio(GRWR),ABO compatibility,recipient body mass index(BMI),recipient tumor diameter,recipient tumor number,recipient tumor differentiation degree,recipient preoperative alpha fetoprotein(AFP)were related factors influencing the overall survival of recipients(hazard ratio=6.26,1.90,2.47,4.08,0.55,5.16,3.62,5.28,2.65,95%confidence interval as 3.01‒13.03,1.07‒3.38,1.36‒4.49,2.07‒8.03,0.31‒0.98,2.56‒10.42,1.95‒6.72,1.60‒17.42,1.48‒5.01,P<0.05)and the donor liver CIT,GRWR,ABO compatibility,recipient tumor diameter,recipient tumor number,recipient tumor differentiation degree,recipient preoperative AFP were related factors influencing the tumor recurrence free survival of recipients(hazard ratio=4.24,2.53,4.05,3.39,3.10,5.19,2.63,95%confidence interval as 2.50‒7.21,1.54‒4.17,2.12‒7.72,2.04‒5.62,1.91‒5.03,2.04‒13.18,1.61‒4.30,P<0.05).Results of multivariate analysis showed that donor liver CIT≥8 hours,GRWR≥2.5%,recipient tumor diameter≥8 cm and recipient preoperative AFP≥400μg/L were independent risk factors influencing the overall survival of recipients(hazard ratio=4.21,2.58,4.10,2.27,95%confidence interval as 1.98‒8.96,1.24‒5.35,1.35‒12.43,1.13‒4.56,P<0.05)and donor liver CIT≥8 hours,GRWR≥2.5%,recipient tumor diameter≥8 cm,recipient tumor number≥3 and recipient preoperative AFP≥400μg/L were independent risk factors influencing the tumor recurrence free survival of recipients(hazard ratio=3.37,2.63,2.42,2.12,2.22,95%confidence interval as 1.70‒6.67,1.40‒4.96,1.04‒5.66,1.08‒4.18,1.26‒3.90,P<0.05).(3)Construction and validation of nomogram prediction model for overall survival and tumor recurrence free survival of recipients.The donor live CIT,GRWR,recipient tumor diameter,recipient preoperative AFP were used to construct nomogram prediction model for overall survival of recipients and the donor liver CIT,GRWR,recipient tumor diameter,recipient tumor number,recipient preoperative AFP were used to construct nomogram prediction model for tumor recurrence free survival of recipients.The ROC curve showed that the AUC of the nomogram prediction model for overall survival of recipients was 0.84(95%confidence interval as 0.76‒0.92,P<0.05),with the optimal diagnostic value as 7.3 and the specificity and sensitivity as 87.6%and 70.0%.The AUC of the nomogram prediction model for tumor recurrence free survival of recipients was 0.79(95%confidence interval as 0.71‒0.87,P<0.05),with the optimal diagnostic value as 5.8 and the specificity and sensitivity as 97.4%and 52.5%.The calibration curve showed that the nomogram prediction model had good distinction for high risk recipients in overall survival and tumor recurrence free survival.Conclusion Donor liver CIT≥8 hours,GRWR≥2.5%,recipient tumor diameter≥8 cm and recipient preoperative AFP≥400μg/L are independent risk factors influencing the overall survival of recipients who underwent LT for HCC using steatotic donor liver and donor liver CIT≥8 hours,GRWR≥2.5%,recipient tumor diameter≥8 cm,recipient tumor number≥3 and recipient preoperative AFP≥400μg/L are independent risk factors influencing the tumor recurrence free survival of recipients.
作者 杨梦凡 王睿 潘斌华 苏仁义 董思依 徐骁 郑树森 魏绪勇 Yang Mengfan;Wang Rui;Pan Binhua;Su Renyi;Dong Siyi;Xu Xiao;Zheng Shusen;Wei Xuyong(Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Hepatobiliary and Pancreatic Surgery,the Center for Integrated Oncology and Precision Medicine,the Affiliated Hangzhou First People′s Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China;National Center for Healthcare Quality Management in Liver Transplantation,Hangzhou 310003,China;Department of Hepatobiliary and Pancreatic Surgery,Shulan(Hangzhou)Hospital,Hangzhou 310022,China)
出处 《中华消化外科杂志》 CAS CSCD 北大核心 2022年第2期237-248,共12页 Chinese Journal of Digestive Surgery
基金 国家重点研发计划(2021YFA1100500) 国家自然科学基金(81702858,81930016,92159202) 浙江省科技厅重点研发计划(2019C03050,2022C03108) 浙江省医药卫生科技计划项目(2016KYB087,2018KY375)。
关键词 肝肿瘤 肝移植 脂肪变性供肝 预后 肿瘤复发 列线图 Liver neoplasms Liver transplantation Steatotic donor liver Prognosis Tumor recurrence Nomogram
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