突破供肝短缺难题：异种肝移植的发展与创新

李霄; 窦科峰

doi:10.3969/j.issn.1001-5256.2022.10.001

突破供肝短缺难题：异种肝移植的发展与创新

DOI: 10.3969/j.issn.1001-5256.2022.10.001

李霄,
窦科峰^, ,

空军军医大学西京医院肝胆外科，全军器官移植研究所，西安 710032

基金项目:

国家自然科学基金 (82070681);

国家自然科学基金 (82170667);

国家自然科学基金 (82070671);

国家自然科学基金 (81970566);

陕西省自然科学基础研究计划 (2022JM-537);

西京医院学科助推计划 (XJZT21CM14);

医学科研项目 (AKJ19J001);

医学科研项目 (18CXZ014)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：李霄负责文献检索，撰写论文；窦科峰负责指导撰写文章并最终定稿。

详细信息

通信作者:
窦科峰，doukef@fmmu.edu.cn

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- 被引次数: 0
出版历程
- 收稿日期: 2022-08-01
- 录用日期: 2022-08-31
- 出版日期: 2022-10-20

Development and progress of liver xenotransplantation: A potential breakthrough for current shortage of donor liver

Xiao LI,
Kefeng DOU^{,
,}

Department of Hepato-Biliary Surgery and Army Institute of Organ Transplantation, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, China

Research funding:

National Natural Science Foundation of China (82070681);

National Natural Science Foundation of China (82170667);

National Natural Science Foundation of China (82070671);

National Natural Science Foundation of China (81970566);

Shaanxi Natural Science Basic Research Project (2022JM-537);

Xijing Hospital Discipline Assistance Program Supporting Project (XJZT21CM14);

Medical Research Project (AKJ19J001);

Medical Research Project (18CXZ014)

More Information

Corresponding author: DOU Kefeng, doukef@fmmu.edu.cn(ORCID: 0000-0002-8857-5663)

摘要

摘要: 供肝短缺是目前影响肝移植发展的最大难题。以2-1，3-牛乳糖苷转移酶基因敲除小型猪为供体的肝移植，在非人灵长类动物体内最长存活近1个月，已初步具备进入临床试验的条件。综合异种肝移植特点及临床现实情况，将异种肝移植作为暴发性肝功能衰竭的“桥接移植”可能是目前异种肝移植进入临床的最佳切入点。本文试就异种肝移植的发展历程、目前的研究进展以及未来临床试验受体选择的标准进行综述和分析，希望对未来的临床异种移植研究提供参考。
- 肝移植 /
- 移植, 异种 /
- 动物, 基因修饰
Abstract: The donor liver shortage is the bottles-neck limitation for clinical liver transplantation to save patients' life. Liver transplantation is a treatment option for end-stage liver diseases, like Cirrhosis and hepatocellular carcinoma, and acute liver failure; however, due to availability of donor liver, lots of patients never received such treatment option and passed way. Most recently, non-human primates after a liver transplantation with GTKO pigs survived for nearly 1 month indicates a promise of clinical use of liver xenotransplantation and could offer "a bridge transplantation" for fulminant liver failure patients. This review discussed and summarized the advancement and progress in the field, i.e., history of liver xenotransplantation research, model animals, clinical selection criteria, and future research directions and clinical trials.
- Liver Transplantation /
- Transplantation, Heterologous /
- Animals, Genetically Modified

HTML全文

表 1 英国NHS急性肝衰竭超紧急选择标准

Table 1. Uperurgent selection criteria proposed by the United Kingdom NHS

病因	纳入和排除标准
对乙酰氨基酚中毒	标准1：液体复苏治疗24 h后，血清pH＜7.24
	标准2：同时存在以下3种情形：(1)凝血酶原时间＞100 s或INR＞6.5；(2)血清肌酐＞300 μmol/L或无尿；(3)3~4级脑病
	标准3：在充分的液体复苏后排除其他原因的高乳酸血症，出现显著肝损伤和凝血功能障碍，入院时动脉乳酸＞5 mmol/L，24 h后出现临床肝性脑病时动脉乳酸＞4 mmol/L
	标准4：无临床败血症的情况下，第2、3条标准中符合2条，并有临床症状恶化的证据(颅内压增加、正性肌力药需求增加)
急性病毒性肝炎或毒品造成的急性肝衰竭	标准5：存在肝性脑病，凝血酶原时间＞100 s，或INR＞6.5，或符合以下情况中的3条，年龄＞40岁或＜10岁；凝血酶原时间＞50 s或INR＞3.5；任何级别的肝性脑病伴黄疸到脑病时间＞7 d；血清胆红素＞300 μmol/L
血清反应阴性或特异性药物反应	标准6：凝血酶原时间＞100 s，或INR＞6.5；或无肝性脑病，补充维生素K后INR＞2，以及符合下述情况中的2项，年龄＞40岁或50岁，INR＞3.5；如果存在肝性脑病，则黄疸到脑病时间＞7 d；血清胆红素＞300 μmol/L
Wilson病或布加综合征诱发急性肝衰竭	标准7：同时存在凝血功能障碍和任何级别的脑病

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