高龄肝移植受者预后和影响因素分析的多中心研究

Prognosis and influencing factors analysis of liver transplantation elderly recipients: a multicenter study

  • 摘要:
    目的 探讨高龄肝移植受者预后和影响因素。
    方法 采用回顾性队列研究方法。收集2015年1月至2020年6月3家医疗中心收治的400例(浙江大学医学院附属第一医院368例、浙江大学医学院附属杭州市第一人民医院17例和青岛大学附属医院15例)肝移植受者的临床病理资料;男297例,女103例;中位年龄为60岁,年龄范围为22~75岁。400例肝移植受者中,200例年龄≥60岁为高龄肝移植受者(ER)设为ER组,200例年龄<60岁为非高龄肝移植受者(NER)设为NER组。受者均行经典原位肝移植或改良背驮式肝移植。观察指标:(1)两组受者和移植物生存情况。(2)肝移植受者死亡的影响因素分析。(3)ER组的分层分析。采用门诊、电话方式进行随访,了解受者生存预后情况。随访时间截至2021年5月。正态分布的计量资料以x±s表示,组间比较采用t检验。计数资料以绝对数表示,组间比较采用χ²检验。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。单因素和多因素分析采用COX回归模型。
    结果 (1)两组受者和移植物生存情况:400例受者均获得随访,随访时间为1 d至71.7个月,中位随访时间为16.3个月。生存分析结果显示:ER组1、3年总体生存率(OS)分别为72.70%、60.66%,1、3年移植物生存率(GS)分别为72.70%、59.64%;NER组1、3年OS分别为78.84%、75.48%,1、3年GS分别为78.84%、74.22%;两组受者总体生存情况和移植物生存情况比较,差异均有统计学意义(χ²=5.712,5.681,P<0.05)。(2)肝移植受者死亡的影响因素分析:单因素分析结果显示年龄、终末期肝病模型评分、Child‑Pugh评分、供肝冷缺血时间(CIT)、合并高血压病、供受者血型、术中出血量、术中红细胞输入量、术中血浆输入量、术中晶体液输入量、术后7 d内最高丙氨酸氨基转移酶、术后7 d内最高天冬氨酸氨基转移酶(AST)、总胆红素(TBil)是影响肝移植受者死亡的相关因素(优势比=1.026,1.022,1.084、1.070、1.701、2.728、1.000、1.056、1.089、1.000、1.000、1.000、1.003,95%可信区间为1.006~1.045,1.005~1.040,1.060~1.170,1.011~1.132,1.133~2.554,1.701~4.374,1.000~1.001,1.031~1.082,1.039~1.142,1.000~1.003,1.001~1.004,1.000~1.002,1.001~1.004,P<0.05)。多因素分析结果显示:年龄、供受者血型、术后7 d内最高AST、TBil是肝移植受者死亡的独立影响因素(优势比=1.022,2.761,1.000,1.007,95%可信区间为1.001~1.044,1.612~4.727,1.000~1.001,1.002~1.012,P<0.05)。(3)ER组的分层分析:①ER组200例受者中,0 h≤CIT≤8 h、8 h<CIT≤12 h、CIT>12 h受者分别为96、73、31例,其1年OS分别为77.46%、73.33%、54.07%,3年OS分别为62.67%、65.05%、41.30%,3者总体生存情况比较,差异有统计学意义(χ²=6.708,P<0.05)。②ER组200例受者中,供受者ABO血型相容、供受者ABO血型不相容受者分别为182、18例,1年OS分别为77.32%、27.78%,3年OS分别为64.63%、22.22%,两者总体生存情况比较,差异有统计学意义(χ²=23.165,P<0.05)。
    结论 ER的总体生存情况差于NER,年龄、供受者血型、术后7 d内最高AST、TBil是肝移植受者死亡的独立影响因素。缩短供肝CIT(<12 h)及避免ABO血型不相容肝移植可以延长ER生存时间。

     

    Abstract:
    Objective To investigate the prognosis of liver transplantation (LT) elderly recipients and analyze the influencing factors for prognosis.
    Methods The retrospective cohort study was conducted. The clinicopathological data of 400 LT recipients who were admitted to three medical centers from January 2015 to June 2020 were collected, including 368 cases in the First Affiliated Hospital of Zhejiang University School of Medicine, 17 cases in the Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine and 15 cases in the Affiliated Hospital of Qingdao University. There were 297 males and 103 females, aged from 22 to 75 years, with a median age of 60 years. Of the 400 LT recipients,200 cases aged ≥60 years were divided into elderly recipients (ER) group and 200 cases aged <60 years were divided into non-elderly recipients (NER) group. Reci-pients underwent orthotopic LT or modified piggyback LT. Observation indicators: (1) survival of recipients and grafts for two groups; (2) influencing factors for death of LT recipients; (3) stratification analysis of ER group. Follow-up using the outpatient examination and telephone interview was conducted to detect survival and prognosis of patients up to May 2021. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rates and draw survival curves. Log-Rank test was used for survival analysis. COX regression model was used for univariate and multivariate analyses.
    Results (1) Survival of recipients and grafts for two groups: 400 recipients were followed up for 1 day to 71.7 months, with a median follow-up time of 16.3 months. Survival analysis showed that the 1-, 3-year overall survival rates and 1-, 3-year graft survival rates for ER group were 72.70%, 60.66% and 72.70%, 59.64%, respectively, versus 78.84%, 75.48% and 78.84%, 74.22% for NER group, showing significant differences in the overall survival and graft survival between the two groups (χ2=5.712, 5.681, P<0.05). (2) Influencing factors for death of LT recipients: results of univariate analysis showed that age, score of model for end stage liver disease, Child-Pugh score, cold ischemia time(CIT) of liver donor, hypertension, blood type of recipients and donors, volume of intraoperative blood loss, volume of intraoperative red blood cell transfusion, volume of intraoperative plasma transfusion, volume of intraoperative crystalloid fluid transfusion, the maximum alanine aminotransferase within postoperative 7 days, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were related factors for death of LT recipients (odds ratio=1.026, 1.022, 1.084, 1.070, 1.701, 2.728, 1.000, 1.056, 1.089, 1.000, 1.000, 1.000, 1.003, 95% confidence interval as 1.006-1.045, 1.005-1.040, 1.060-1.170, 1.011-1.132, 1.133-2.554, 1.701-4.374, 1.000-1.001, 1.031-1.082, 1.039-1.142, 1.000-1.003, 1.001-1.004, 1.000-1.002, 1.001-1.004, P<0.05). Results of multivariate analysis showed that age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were independent influencing factors for death of LT recipients (odds ratio=1.022, 2.761, 1.000, 1.007, 95% confidence interval as 1.001-1.044, 1.612-4.727, 1.000-1.001, 1.002-1.012, P<0.05). (3) Stratification analysis of ER group: ① of 200 recipients in ER group, cases with 0 hour≤CIT≤8 hours, 8 hours<CIT≤12 hours, CIT>12 hours were 96, 73, 31 ,respectively. The 1-year overall survival rates for above recipients were 77.46%, 73.33%, 54.07%, and the 3-year overall survival rates were 62.67%, 65.05%, 41.30%. There was a significant difference in the overall survival between the three groups (χ2=6.708, P<0.05). ② Of 200 recipients in ER group,182 cases were ABO compatible and 18 were ABO incompatible. The 1-year overall survival rates for above recipients were 77.32%, 27.78%, and the 3-year overall survival rates were 64.63%, 22.22%. There was a significant difference in the overall survival between the two groups (χ2=23.165, P<0.05).
    Conclusions The overall survival of ER is inferior to NER. Age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin are indepen-dent influencing factors for death of LT recipients. Controlling CIT within 12 hours and avoiding ABO incompatible-liver transplantation can significantly improve the prognosis of ER.

     

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