供肝保存与功能维护助力肝移植发展

谢炎; 蒋文涛

doi:10.3969/j.issn.1674-7445.2023.02.004

供肝保存与功能维护助力肝移植发展

doi: 10.3969/j.issn.1674-7445.2023.02.004

谢炎,
蒋文涛^,

300190 天津，天津市第一中心医院肝移植科天津市器官移植重点实验室南开大学移植医学研究院

基金项目:

国家自然科学基金面上项目 81870444

天津市卫生健康委员会重点学科专项 TJWJ2022XK016

天津市自然科学基金面上项目 20JCYBJC01010

详细信息

作者简介:

通讯作者:
蒋文涛，Email：jiangwentao@nankai.edu.cn

中图分类号: R617
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- 被引次数: 0
出版历程
- 收稿日期: 2023-01-29
- 网络出版日期: 2023-03-15
- 刊出日期: 2023-03-15

Liver graft preservation and functional maintenance accelerate the development of liver transplantation

Xie Yan,
Jiang Wentao^,

Department of Liver Transplantation, Tianjin First Center Hospital, Tianjin Key Laboratory for Organ Transplantation, Research Institute of Transplant Medicine, Nankai University, Tianjin 300190, China

More Information

Corresponding author: Jiang Wentao, Email: jiangwentao@nankai.edu.cn

摘要

摘要: 肝移植作为终末期肝病的有效治疗方法已在世界范围内广泛开展，并逐渐取得普遍认可。随着肝移植手术技术趋于成熟，术后并发症发生率逐步降低，受者的短期和长期预后持续改善。然而，器官的供应与需求之间一直存在着巨大鸿沟，是限制肝移植手术开展的重要原因。国内肝移植手术量逐年上升，供肝短缺问题日益突出，边缘供肝越来越多地应用于临床。近年来，供者器官的选择标准、器官的保存及功能维护技术不断完善。本文将从供肝保存、功能维护两方面，结合二者近年来的技术发展和研究成果，评述不同技术的应用情况和发展趋势，为进一步提高移植物和受者生存率，促进我国肝移植的发展提供参考。
- 肝移植 /
- 边缘供肝 /
- 静态冷保存 /
- 机械灌注 /
- 缺血-再灌注损伤 /
- 功能维护 /
- 基因治疗 /
- 干细胞疗法
Abstract: As an effective treatment for end-stage liver disease, liver transplantation has been widely carried out worldwide and gradually captivated widespread recognition. With the advancement of liver transplantation techniques, the incidence of postoperative complications has been gradually declined, and the short-term and long-term prognosis of recipients have been constantly improved. However, a huge gap has existed between the supply and demand of donor organs, which is a major factors restricting the development of liver transplantation. The amount of liver transplantation operation in China is increasing year by year, the shortage of donor liver is becoming more and more prominent, and marginal donor liver is increasingly used in clinic. In recent years, the selection criteria of donor organs, organ preservation and functional maintenance have been continuously improved. In this article, the application and development trend of different techniques were reviewed from the perspectives of donor liver preservation and functional maintenance, and recent technical development and research results were summarized, aiming to provide reference for further enhancing the survival rate of grafts and recipients and promoting the development of liver transplantation in China.
- Liver transplantation /
- Marginal liver graft /
- Static cold storage /
- Machine perfusion /
- Ischemia-reperfusion injury /
- Functional maintenance /
- Gene therapy /
- Stem cell therapy

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参考文献(35)

[1]	LIN Y, HUANG H, CHEN L, et al. Assessing donor liver quality and restoring graft function in the era of extended criteria donors[J]. J Clin Transl Hepatol, 2023, 11(1): 219-230. DOI: 10.14218/JCTH.2022.00194.
[2]	XIA C, DONG X, LI H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl), 2022, 135(5): 584-590. DOI: 10.1097/CM9.0000000000002108.
[3]	CHEN Z, HONG X, HUANG S, et al. Continuous normothermic machine perfusion for renovation of extended criteria donor livers without recooling in liver transplantation: a pilot experience[J]. Front Surg, 2021, 8: 638090. DOI: 10.3389/fsurg.2021.638090.
[4]	PESCARISSI C, PENZO B, GHINOLFI D, et al. The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres[J]. BMC Anesthesiol, 2022, 22(1): 390. DOI: 10.1186/s12871-022-01932-x.
[5]	AMIN A, PANAYOTOVA G, GUARRERA JV. Hypothermic machine perfusion for liver graft preservation[J]. Curr Opin Organ Transplant, 2022, 27(2): 98-105. DOI: 10.1097/MOT.0000000000000973.
[6]	JAKUBAUSKAS M, JAKUBAUSKIENE L, LEBER B, et al. Machine perfusion in liver transplantation: a systematic review and meta-analysis[J]. Visc Med, 2022, 38(4): 243-254. DOI: 10.1159/000519788.
[7]	JOCHMANS I, BRAT A, DAVIES L, et al. Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial[J]. Lancet, 2020, 396(10263): 1653-1662. DOI: 10.1016/S0140-6736(20)32411-9.
[8]	TINGLE SJ, FIGUEIREDO RS, MOIR JA, et al. Machine perfusion preservation versus static cold storage for deceased donor kidney transplantation[J]. Cochrane Database Syst Rev, 2019, 3(3): CD011671. DOI: 10.1002/14651858.CD011671.pub2.
[9]	BARDALLO RG, DA SILVA RT, CARBONELL T, et al. Liver graft hypothermic static and oxygenated perfusion (HOPE) strategies: a mitochondrial crossroads[J]. Int J Mol Sci, 2022, 23(10): 5742. DOI: 10.3390/ijms23105742.
[10]	SCHLEGEL A, MULLER X, MUELLER M, et al. Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation[J]. EBioMedicine, 2020, 60: 103014. DOI: 10.1016/j.ebiom.2020.103014.
[11]	MUGAANYI J, DAI L, LU C, et al. A meta-analysis and systematic review of normothermic and hypothermic machine perfusion in liver transplantation[J]. J Clin Med, 2022, 12(1): 235. DOI: 10.3390/jcm12010235.
[12]	SOUSA DA SILVA RX, WEBER A, DUTKOWSKI P, et al. Machine perfusion in liver transplantation[J]. Hepatology, 2022, 76(5): 1531-1549. DOI: 10.1002/hep.32546.
[13]	CZIGANY Z, PRATSCHKE J, FRONĚK J, et al. Hypothermic oxygenated machine perfusion reduces early allograft injury and improves post-transplant outcomes in extended criteria donation liver transplantation from donation after brain death: results from a multicenter randomized controlled trial (HOPE ECD-DBD)[J]. Ann Surg, 2021, 274(5): 705-712. DOI: 10.1097/SLA.0000000000005110.
[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. DOI: 10.1016/j.jhep.2018.10.005.
[15]	MARTINS PN, BUCHWALD JE, MERGENTAL H, et al. The role of normothermic machine perfusion in liver transplantation[J]. Int J Surg, 2020, 82S: 52-60. DOI: 10.1016/j.ijsu.2020.05.026.
[16]	NASRALLA D, COUSSIOS CC, MERGENTAL H, et al. A randomized trial of normothermic preservation in liver transplantation[J]. Nature, 2018, 557(7703): 50-56. DOI: 10.1038/s41586-018-0047-9.
[17]	WATSON CJE, HUNT F, MESSER S, et al. In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival[J]. Am J Transplant, 2019, 19(6): 1745-1758. DOI: 10.1111/ajt.15241.
[18]	HESSHEIMER AJ, COLL E, TORRES F, et al. Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation[J]. J Hepatol, 2019, 70(4): 658-665. DOI: 10.1016/j.jhep.2018.12.013.
[19]	GAURAV R, BUTLER AJ, KOSMOLIAPTSIS V, et al. Liver transplantation outcomes from controlled circulatory death donors: SCS vs in situ NRP vs ex situ NMP[J]. Ann Surg, 2022, 275(6): 1156-1164. DOI: 10.1097/SLA.0000000000005428.
[20]	RUIZ P, GASTACA M, BUSTAMANTE FJ, et al. Favorable outcomes after liver transplantation with normothermic regional perfusion from donors after circulatory death: a single-center experience[J]. Transplantation, 2019, 103(5): 938-943. DOI: 10.1097/TP.0000000000002391.
[21]	BOTEON YL, AFFORD SC, MERGENTAL H. Pushing the limits: machine preservation of the liver as a tool to recondition high-risk grafts[J]. Curr Transplant Rep, 2018, 5(2): 113-120. DOI: 10.1007/s40472-018-0188-7.
[22]	LINARES I, HAMAR M, SELZNER N, et al. Steatosis in liver transplantation: current limitations and future strategies[J]. Transplantation, 2019, 103(1): 78-90. DOI: 10.1097/TP.0000000000002466.
[23]	NAGRATH D, XU H, TANIMURA Y, et al. Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo[J]. Metab Eng, 2009, 11(4/5): 274-283. DOI: 10.1016/j.ymben.2009.05.005.
[24]	LIU Q, NASSAR A, BUCCINI L, et al. Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion[J]. Liver Transpl, 2018, 24(2): 233-245. DOI: 10.1002/lt.24972.
[25]	WANG WC, SAYEDAHMED EE, MITTAL SK. Significance of preexisting vector immunity and activation of innate responses for adenoviral vector-based therapy[J]. Viruses, 2022, 14(12): 2727. DOI: 10.3390/v14122727.
[26]	CHOWDARY P, SHAPIRO S, MAKRIS M, et al. Phase 1-2 trial of AAVS3 gene therapy in patients with hemophilia B[J]. N Engl J Med, 2022, 387(3): 237-247. DOI: 10.1056/NEJMoa2119913.
[27]	BONACCORSI-RIANI E, GILLOOLY AR, IESARI S, et al. Delivering siRNA compounds during HOPE to modulate organ function: a proof-of-concept study in a rat liver transplant model[J]. Transplantation, 2022, 106(8): 1565-1576. DOI: 10.1097/TP.0000000000004175.
[28]	TCHKONIA T, KIRKLAND JL. Aging, cell senescence, and chronic disease: emerging therapeutic strategies[J]. JAMA, 2018, 320(13): 1319-1320. DOI: 10.1001/jama.2018.12440.
[29]	LI J, PENG Q, YANG R, et al. Application of mesenchymal stem cells during machine perfusion: an emerging novel strategy for organ preservation[J]. Front Immunol, 2021, 12: 713920. DOI: 10.3389/fimmu.2021.713920.
[30]	VERSTEGEN MMA, MEZZANOTTE L, RIDWAN RY, et al. First report on ex vivo delivery of paracrine active human mesenchymal stromal cells to liver grafts during machine perfusion[J]. Transplantation, 2020, 104(1): e5-e7. DOI: 10.1097/TP.0000000000002986.
[31]	TIETJEN GT, BRACAGLIA LG, SALTZMAN WM, et al. Focus on fundamentals: achieving effective nanoparticle targeting[J]. Trends Mol Med, 2018, 24(7): 598-606. DOI: 10.1016/j.molmed.2018.05.003.
[32]	STEPHENSON BTF, BONNEY GK, LAING RW, et al. Proof of concept: liver splitting during normothermic machine perfusion[J]. J Surg Case Rep, 2018(3): rjx218. DOI: 10.1093/jscr/rjx218.
[33]	SCHLEGEL A, KALISVAART M, SCALERA I, et al. The UK DCD risk score: a new proposal to define futility in donation-after-circulatory-death liver transplantation[J]. J Hepatol, 2018, 68(3): 456-464. DOI: 10.1016/j.jhep.2017.10.034.
[34]	BHOGAL RH, MIRZA DF, AFFORD SC, et al. Biomarkers of liver injury during transplantation in an era of machine perfusion[J]. Int J Mol Sci, 2020, 21(5): 1578. DOI: 10.3390/ijms21051578.
[35]	WATSON CJE, KOSMOLIAPTSIS V, PLEY C, et al. Observations on the ex situ perfusion of livers for transplantation[J]. Am J Transplant, 2018, 18(8): 2005-2020. DOI: 10.1111/ajt.14687.