器官捐献时代再次肝移植单中心回顾性研究

目的总结再次肝移植的病因、预后及并发症防治。 方法回顾性分析2015年1月至2019年12月复旦大学附属华山医院完成的26例再次肝移植供、受者临床资料。根据再次肝移植时间不同，将2015年1月至2017年12月(代表公民逝世后器官捐献时代早期再次肝移植治疗经验探索期)完成的再次肝移植受者纳入早期移植组(共9例)，将2018年1月至2019年12月完成的再次肝移植受者纳入成熟期移植组(共17例)。根据移植间隔时间不同，将26例受者分为移植间隔>1年组(15例)和移植间隔≤1年组(11例)。采用两独立样本t检验比较早期与成熟期移植组受者再次肝移植术前年龄、终末期肝病模型(MELD)评分、手术时长、供肝冷和热缺血时间、无肝期时长及术后第7、14天血清白蛋白水平。采用Mann-Whitney U检验比较两组受者移植间隔时长、术中出血量和输血量以及术后第7、14天总胆红素、ALT和AST。采用Kaplan-Meier法计算再移植术后受者生存率并绘制生存曲线，采用Log-rank检验比较早期与成熟期移植组、移植间隔>1年与≤1年组受者术后2年生存率。P<0.05为差异有统计学意义。 结果再次肝移植病因包括：胆道并发症8例，移植物失功8例，原发病复发4例(肝细胞肝癌复发)，慢性排斥反应2例，首次肝移植术后急性肝功能衰竭2例，血管并发症2例(门静脉血栓和肝动脉栓塞各1例)。早期移植组受者术中无肝期时长和术后第7天血清白蛋白分别为(53.3±7.9)min和(34±5)g/L，成熟期移植组受者分别为(45.1±1.8)min和(38±4)g/L，差异均有统计学意义(t＝3.098和-2.111，P均<0.05)。早期移植组肝移植术前年龄、MELD评分、移植间隔时长、手术时间、术中出血量、术中输血量、供肝冷和热缺血时间、术后第7天总胆红素、ALT和AST以及术后第14天总胆红素、ALT、AST和白蛋白差异均无统计学意义(P均>0.05)。随访至2020年10月1日，26例受者中位随访时间为715 d(105～1 842 d)，期间9例受者均于术后1年内死亡(早期移植组6例，成熟期移植组3例)。早期移植组和成熟期移植组受者术后2年累积生存率分别为33.3%和82.4%，差异有统计学意义(χ²＝6.248，P<0.05)。移植间隔≤1年组和移植间隔>1年组受者术后2年累积生存率分别为54.5%和73.3%，差异无统计学意义(χ²＝0.990，P>0.05)。 结论胆道并发症及移植物失功能是再次肝移植的主要原因，器官捐献成熟时期的再次肝移植预后优于器官捐献时代早期。因再移植受者病情复杂、手术困难，应谨慎进行再次肝移植手术评估。合理的个体化治疗能够为再次肝移植受者带来良好预后。

Single-center retrospective analysis of liver retransplantation in the era of organ donation

ObjectiveTo analyze the causes, complications and prognosis of liver retransplantation. MethodsThe clinical data of 26 liver retransplantation recipients and donors from Huashan Hospital Affiliated to Fudan University from January 2015 to December 2019 were retrospectively analyzed. Among 26 cases, 9 cases were in the early period of organ donation group (January 2015 to December 2017), and 17 cases were in the developed period of organ donation group (January 2018 to December 2019). According to different transplantation intervals, 26 recipients were divided into transplantation interval >1 year group (15 cases) and transplantation interval ≤1 year group (11 cases). Two independent sample t-tests was used to compare the preoperative age, model for end-stage liver disease (MELD) scores, operation duration, warm and cold ischemia time, time of anthepatic phase, and serum albumin levels on the 7th and 14th day after liver transplantation between the early period of organ donation and developed period of organ donation group. The Mann-Whitney U test was used to compare the transplantation interval, intraoperative blood loss and blood transfusion, and total bilirubin, ALT and AST on the 7th and 14th day after liver transplantation between the early period of organ donation and developed period of organ donation group. The Kaplan-Meier method was used to calculate the survival rate of the recipients after liver retransplantation and to draw the survival curve. The Log-rank test was used to compare the 2 years survival rate of the early period between organ donation and developed period of organ donation group, and the transplantation interval >1 year and ≤1 year group. P<0.05 indicates that the difference is statistically significant. ResultsThe causes of retransplantation included: 8 cases of biliary complications, 8 cases of graft failure, 4 cases of primary recurrence (recurrence of hepatocellular carcinoma), 2 cases of chronic rejection, and 2 cases of acute liver failure after the first liver transplantation, 2 cases of vascular complications (1 case each for portal vein thrombosis and 1 case for hepatic artery embolism). The time of anthepatic phase and serum albumin level of recipients on the 7th day after liver transplantation in the early period between organ donation and developed period of organ donation group were (53.3±7.9) and (45.1±1.8) min, (34±5) and (38±4) g/L, respectively, and the differences were statistically significant (t=3.098 and -2.111, all P<0.05 ). There were no statistically significant differences between the early period of organ donation and developed period of organ donation group for the age before liver retransplantation, MELD scores, the transplantation interval, operation time, intraoperative blood loss, intraoperative blood transfusion, warm and cold ischemia time, and total bilirubin, ALT and AST on the 7th and 14th day after retransplantation (all P>0.05). The recipients were followed until October 1, 2020, the median follow-up time was 715 d (105-1 842 d), during which 9 recipients died within 1 year after surgery (6 in the early period of organ donation group, 3 cases in the developed period of organ donation group). The 2- year cumulative survival rate of recipients in the early period between organ donation and developed period of organ donation group were 33.3% and 82.4%, which was statistically significant (χ²=6.248, P<0.05). The cumulative survival rates of recipients in the transplantation interval ≤1 year and transplantation interval >1 year were 54.5% and 73.3%, which had no significant difference (χ²=0.990, P>0.05). ConclusionsBiliary complications and graft failure are the main reasons for retransplantation. The prognosis of retransplantation in the developed period of organ donation is better than that in the early period of organ donation. Given the complicated condition of the retransplant recipient and the difficulty of the operation, the evaluation of the retransplantation operation should be carried out carefully. Reasonable individualized treatment can bring a good prognosis for retransplantation recipients.