切换至 "中华医学电子期刊资源库"
高级检索
中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2020, Vol. 14 ›› Issue (04) : 280 -285. doi: 10.3877/cma.j.issn.1674-0793.2020.04.010

所属专题： 文献；

论著

常温机械灌注修复边缘性供肝的临床疗效：单中心报道
朱财慧1, 汪琳和1, 张志衡1, 戚添媛2, 鞠卫强1, 郭志勇1,†(), 何晓顺1   
  1. 1. 510080　广州，中山大学附属第一医院器官移植科
    2. 510080　广州，中山大学医学院
  • 收稿日期:2020-06-01 出版日期:2020-08-01
  • 通信作者: 郭志勇
  • 基金资助:
    国家自然科学基金资助项目(81970564); 中大高校基本科研业务费青年教师重点培育项目(19ykzd13)

Clinical outcomes of liver transplantation using normothermic machine perfusion: A single center report

Caihui Zhu1, Linhe Wang1, Zhiheng Zhang1, Tianyuan Qi2, Weiqiang Ju1, Zhiyong Guo1,†(), Xiaoshun He1   

  1. 1. Organ Transplant Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
    2. Zhongshan Medical College of Sun Yat-sen University, Guangzhou 510080, China
  • Received:2020-06-01 Published:2020-08-01
  • Corresponding author: Zhiyong Guo
  • About author:
    Corresponding author: Guo Zhiyong, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

朱财慧, 汪琳和, 张志衡, 戚添媛, 鞠卫强, 郭志勇, 何晓顺. 常温机械灌注修复边缘性供肝的临床疗效：单中心报道[J/OL]. 中华普通外科学文献(电子版), 2020, 14(04): 280-285.

Caihui Zhu, Linhe Wang, Zhiheng Zhang, Tianyuan Qi, Weiqiang Ju, Zhiyong Guo, Xiaoshun He. Clinical outcomes of liver transplantation using normothermic machine perfusion: A single center report[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2020, 14(04): 280-285.

目的

探讨常温机械灌注（normothermic machine perfusion, NMP）修复边缘性供肝的安全性和有效性。

方法

2018年9月至2019年9月，使用NMP进行6例边缘性供肝体外评估和修复，供肝来自4例心死亡和2例高胆红素血症患者。记录灌注过程的灌注参数、灌注液血气分析及生化检验指标，结合供肝外观等评估边缘性供肝是否适合移植。术后随访至少3个月，记录移植后7 d内肝功能指标、生化指标、并发症发生情况等。

结果

NMP期间灌注参数稳定，肝动脉灌注流量为110~334 ml/min，门静脉灌注流量为540~1 180 ml/min。灌注液pH、PO2、PCO2在灌注0.5 h后基本恢复正常，乳酸水平迅速下降；肝酶水平无明显升高，胆汁pH>7.5。所有供肝灌注均匀，质地柔软，均被用于移植。受者肝移植后恢复情况良好，无一例发生原发性移植肝无功能或缺血性胆道病变，至末次随访所有患者及移植物均存活。

结论

本科室在临床肝移植中应用NMP技术的初步经验提示，NMP用于边缘性供肝的保存是安全、有效的。

关键词: 边缘性供肝, 常温机械灌注, 肝移植, 早期移植物功能不全, 原发性移植物无功能
Objective

To investigate the safety and efficacy of normothermic machine perfusion (NMP) in resuscitation of marginal donor livers.

Methods

From September 2018 to September 2019, NMP was used for in vitro evaluation and repair of six marginal donor livers. Four livers derived from donation after circulatory death patients, and two from hyperbilirubinemia patients. The perfusion parameters were recorded. Blood gas analysis and biochemical test, bile production were performed to evaluate the viability of the marginal donor livers. All patients were followed up for at least three months after transplantation. Liver function, blood gas indexes and complications were recorded within 7 days after transplantation.

Results

The perfusion parameters were stable during NMP, with hepatic arterial and portal vein perfusion flows of 110-334 ml/min and 540-1 180 ml/min, respectively. pH, PO2, PCO2 returned to normal range after 0.5 hour of perfusion and the lactate levels declined rapidly. There was no significant increase in liver enzymes and pH values of bile produced by livers were higher than 7.5. All the recipients had uneventful recovery from liver transplantation, and no patient suffered from primary nonfunction or ischaemic cholangiopathy. All the patients and grafts survived.

Conclusion

The preliminary experience of liver transplantation using NMP in our department suggests that NMP is safe and effective in resuscitating marginal donor livers.

Key words: Marginal donor livers, Normothermic machine perfusion, Liver transplantation, Early allograft dysfunction, Primary nonfunction
表1 6例边缘性器官移植供受体的基本特征
供受体基线 例1 例2 例3 例4 例5 例6
供体 ? ? ? ? ? ?
? 类型 心死亡捐献 心死亡捐献 心死亡捐献 脑死亡捐献 心死亡捐献 脑死亡捐献
? 年龄(岁) 22 20 26 19 58 47
? 性别 女 男 女 男 男 男
? 死因 脑血管意外 脑血管意外 主动脉夹层 颅脑损伤 脑血管意外 脑干出血
? 热缺血时间(min) 22 10 6 0 5 0
? 冷缺血时间(h) 10.63 9.00 7.00 5.50 4.00 5.50
? 灌注原因 心死亡捐献 心死亡捐献 心死亡捐献 高胆红素血症 心死亡捐献 高胆红素血症
? 灌注时间(min) 260 260 380 360 400 320
受体 ? ? ? ? ? ?
? 年龄(岁) 28 64 58 57 34 62
? 性别 男 男 男 男 男 女
? 诊断 ACLF HCC HCC HCC ACLF ICC
? 手术方式 背驮式 背驮式 经典式 经典式 背驮式 背驮式
? 机械通气时长(h) 62.93 17.38 20.18 10.35 13.85 7.68
? 重症监护时长(h) 83.97 35.65 27.55 61.95 34.50 24.30
? 住院时间(d) 24 15 16 18 17 24
表2 常温机械灌注灌注液成分表
成分 用量
洗涤红细胞 6~10 U
4%琥珀酰明胶注射液 600~1 200 ml
5%碳酸氢钠注射液 100~120 ml
肝素钠注射液(1 ml12 500 U) 37 500 U
葡萄糖酸钙注射液(10 ml 1 g) 40 ml
硫酸镁注射液(10 ml 2.5 g) 4 ml
注射用甲泼尼龙琥珀酸钠(500 mg) 250~500 mg
多种微量元素注射液(Ⅱ) 10 ml
甲硝唑注射液(100 ml 0.5 g) 100 ml
注射用亚胺培南西司他丁钠(500 mg) 1 g
氨基酸注射液(250 ml 12.5 g) 125~250 ml
图1 6例患者常温机械灌注（NMP）灌注参数　A~F分别为灌注过程中门静脉压力、肝动脉压力、门静脉流量、肝动脉流量、门静脉阻力指数、肝动脉阻力指数的变化趋势
图2 6例患者常温机械灌注（NMP）时灌注液的血气分析部分参数变化　A~D分别为灌注过程中灌注液的pH值、PO2、PCO2及乳酸值；例2在NMP的最后2 h内部分乳酸值小于仪器可以监测的最小值0.2 mmol/L，图中均以0.2 mmol/L表示
图3 6例患者常温机械灌注（NMP）时灌注液的肝功能检测　A~C分别为丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素（total bilirubin, TBil）的变化
图4 6例患者常温机械灌注（NMP）时的胆汁血气分析　A~C分别显示显示每小时胆汁的量、pH值及HCO3-；超过血气分析仪上限8.2的pH值在图上用8.2表示
图5 6例患者肝移植术后随访期间肝功能指标　A~D分别为丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素（TBil）、国际标准化比值（INR）变化趋势
[1]
Jayant K, Reccia I, Shapiro A. Normothermic ex-vivo liver perfusion: where do we stand and where to reach?[J]. Expert Rev Gastroenterol Hepatol, 2018, 12(10): 1045-1058.
[2]
op den Dries S, Karimian N, Sutton ME, et al. Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers[J]. Am J Transplant, 2013, 13(5): 1327-1335.
[3]
Watson C, Kosmoliaptsis V, Randle LV, et al. Normothermic perfusion in the assessment and preservation of declined livers before transplantation: hyperoxia and vasoplegia-important lessons from the first 12 cases[J]. Transplantation, 2017, 101(5): 1084-1098.
[4]
Banan B, Chung H, Xiao Z, et al. Normothermic extracorporeal liver perfusion for donation after cardiac death (DCD) livers[J]. Surgery, 2015, 158(6): 1642-1650.
[5]
op den Dries S, Karimian N, Weeder PD, et al. Normothermic acellular machine perfusion and bile duct injury in pig livers retrieved after cardiac death[J]. Am J Transplant, 2013, 13(12): 3289.
[6]
Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation[J]. Nature, 2018, 557(7703): 50-56.
[7]
Nakamura A, Osonoi T, Terauchi Y. Relationship between urinary sodium excretion and pioglitazone-induced edema[J]. J Diabetes Investig, 2010, 1(5): 208-211.
[8]
Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors[J]. Liver Transpl, 2010, 16(8): 943-949.
[9]
Huang J, Millis JM, Mao Y, et al. Voluntary organ donation system adapted to Chinese cultural values and social reality[J]. Liver Transpl, 2015, 21(4): 419-422.
[10]
van Leeuwen OB, de Vries Y, Fujiyoshi M, et al. Transplantation of high-risk donor livers after ex situ resuscitation and assessment using combined hypo- and normothermic machine perfusion: A prospective clinical trial[J]. Ann Surg, 2019, 270(5): 906-914.
[11]
Graham JA, Guarrera JV. "Resuscitation" of marginal liver allografts for transplantation with machine perfusion technology[J]. J Hepatol, 2014, 61(2): 418-431.
[12]
Monbaliu D, Liu Q, Libbrecht L, et al. Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: A proof-of-concept study using discarded human livers[J]. Liver Transpl, 2012, 18(12): 1495-1507.
[13]
Raigani S, Markmann JF, Yeh H. Rehabilitation of discarded steatotic livers using ex situ normothermic machine perfusion: A future source of livers for transplantation[J]. Liver Transpl, 2019, 25(7): 991-992.
[14]
Schlegel A, Muller X, Kalisvaart M, et al. Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation[J]. J Hepatol, 2019, 70(1): 50-57.
[15]
He X, Guo Z, Zhao Q, et al. The first case of ischemia-free organ transplantation in humans: A proof of concept[J]. Am J Transplant, 2018, 18(3): 737-744.
[16]
Laing RW, Mergental H, Yap C, et al. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial[J]. BMJ Open, 2017, 7(11): e017733.
[17]
Matton APM, de Vries Y, Burlage LC, et al. Biliary bicarbonate, pH, and glucose are suitable biomarkers of biliary viability during ex situ normothermic machine perfusion of human donor livers[J]. Transplantation, 2019, 103(7): 1405-1413.
[18]
Schön MR, Kollmar O, Wolf S, et al. Liver transplantation after organ preservation with normothermic extracorporeal perfusion[J]. Ann Surg, 2001, 233(1): 114-123.
[19]
Jayant K, Reccia I, Virdis F, et al. The role of normothermic perfusion in liver transplantation (TRaNsIT Study): A systematic review of preliminary studies[J]. HPB Surg, 2018, 2018: 6360423.
[20]
Dutkowski P, Guarrera JV, de Jonge J, et al. Evolving trends in machine perfusion for liver transplantation[J]. Gastroenterology, 2019, 156(6): 1542-1547.
[1] 陈进宏. 腹腔镜活体供肝获取规范与创新[J/OL]. 中华普通外科学文献(电子版), 2024, 18(05): 324-324.
[2] 中华医学会器官移植学分会, 中国医师协会器官移植医师分会. 中国活体肝移植供者微创手术技术指南（2024版）[J/OL]. 中华普通外科学文献(电子版), 2024, 18(04): 241-252.
[3] 仲福顺, 余露, 范晓礼, 叶啟发. 肝移植治疗肝上皮样血管内皮瘤一例[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 293-297.
[4] 刘冉佳, 崔向丽, 周效竹, 曲伟, 朱志军. 儿童肝移植受者健康相关生存质量评价的荟萃分析[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 302-309.
[5] 贺健, 张骊, 王洪海, 蒋文涛. 肝移植术后脾功能亢进转归及治疗研究进展[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 310-314.
[6] 胡宁宁, 赵延荣, 王栋, 王胜亮, 郭源. FMNL3与肝细胞癌肝移植受者预后的相关性研究[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 283-288.
[7] 王淑贤, 张良灏, 王利君, 张慧, 郭源, 许传屾, 李志强, 蔡金贞, 解曼, 饶伟. 成人肝移植围手术期严重心血管事件危险因素分析及预测模型研究[J/OL]. 中华移植杂志(电子版), 2024, 18(04): 222-229.
[8] 张丽娜, 邢建坤, 张梁, 李云生, 王兢, 孙丽莹, 朱志军. 婴幼儿活体肝移植受者术中麻醉护理单中心经验[J/OL]. 中华移植杂志(电子版), 2024, 18(04): 235-238.
[9] 黄建朋, 邹建强, 宗华. 肝移植术后腹壁疝诊治初步经验[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(04): 471-473.
[10] 魏志鸿, 刘建勇, 吴小雅, 杨芳, 吕立志, 江艺, 蔡秋程. 肝移植术后急性移植物抗宿主病的诊治（附四例报告）[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 846-851.
[11] 中华医学会器官移植学分会. 肝移植术后缺血性胆道病变诊断与治疗中国实践指南[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 739-748.
[12] 傅斌生, 冯啸, 杨卿, 曾凯宁, 姚嘉, 唐晖, 刘剑戎, 魏绪霞, 易慧敏, 易述红, 陈规划, 杨扬. 脂肪变性供肝在成人劈离式肝移植中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 789-794.
[13] 中华医学会器官移植学分会, 中华医学会外科学分会外科手术学学组, 中华医学会外科学分会移植学组, 华南劈离式肝移植联盟. 劈离式供肝儿童肝移植中国临床操作指南[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 593-601.
[14] 刘军, 丘文静, 孙方昊, 李松盈, 易述红, 傅斌生, 杨扬, 罗慧. 在体与离体劈离式肝移植在儿童肝移植中的应用比较[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 688-693.
[15] 张红君, 郑博文, 廖梅, 任杰. 超声及超声造影在肝移植术后上腹部淋巴结良恶性鉴别诊断中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(04): 562-567.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号