Research progress of machine perfusion in donor liver preservation

doi:10.3877/cma.j.issn.1674-3903.2021.03.013

Abstract

Abstract:

Liver transplantation is one of the main treatments for end-stage liver disease, and good donor liver preservation techniques play an important role in the successful implementation of liver transplantation. At present, the static cold storage (SCS) technique, which is widely used in clinical practice, still faces the shortcomings of short preservation time and ischemia-reperfusion injury, which affects the prognosis of liver transplantation. In recent years, the machine perfusion (MP) for isolated donor liver preservation has been developed. It mainly uses mechanical power to continuously pump the perfusate into the donor liver to remove metabolic waste while providing metabolic substrates. Compared with SCS, MP has the advantages of prolonging the preservation time and improving the quality of donor organs, and MP also shows certain advantages for the preservation of donor liver from extended criteria donor. However, MP also has disadvantages such as higher cost, complicated instrument system and less clinical research, which limits its application. Studies on MP preservation of donor livers are currently at the forefront of organ preservation research, mainly focusing on the preservation, assessment, and restoration of donor liver. Here we reviewed the recent research progress of MP and its important role in the quality assessment and restoration of donor liver.

Key words: Liver transplantation, Machine perfusion, Hypothermic perfusion, Quality assessment

Lifeng Chen, Hengjie Huang, Ren Yan, Qi Ling. Research progress of machine perfusion in donor liver preservation[J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(03): 183-188.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhyzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3903.2021.03.013

https://zhyzzz.cma-cmc.com.cn/EN/Y2021/V15/I03/183

References 55

1	Merion RM, Goodrich NP, Feng s. How can we define expanded criteria for liver donors？[J]. J Hepatol, 2006, 45(4): 484-488.
2	Chouchani ET, Pell VR, Gaude E, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS[J]. Nature, 2014, 515(7527): 431-435.
3	Sibulesky L, Li M, Hansen RN, et al. Impact of cold ischemia time on outcomes of liver transplantation: a single center experience[J]. Ann Transplant, 2016, 21: 145-151.
4	Stahl JE, Kreke JE, Malek FA, et al. Consequences of cold-ischemia time on primary nonfunction and patient and graft survival in liver transplantation: a meta-analysis[J]. PLoS One, 2008, 3(6): e2468.
5	St Peter SD, Imber CJ, Friend PJ. Liver and kidney preservation by perfusion[J]. Lancet, 2002, 359(9306): 604-613.
6	Deshpande R, Heaton N. Can non-heart-beating donors replace cadaveric heart-beating liver donors？[J]. J Hepatol, 2006, 45(4): 499-503.
7	Dutkowski P, de Rougemont O, Clavien PA. Machine perfusion for 'marginal’ liver grafts[J]. Am J Transplant, 2008, 8(5): 917-924.
8	Starzl TE, Groth CG, Brettschneider L, et al. Extended survival in 3 cases of orthotopic homotransplantation of the human liver[J]. Surgery, 1968, 63(4): 549-563.
9	Butler AJ, Rees MA, Wight DG, et al. Successful extracorporeal porcine liver perfusion for 72 hr[J]. Transplantation, 2002, 73(8): 1212-1218.
10	Vajdová K, Smreková R, Mislanová C, et al. Cold-preservation-induced sensitivity of rat hepatocyte function to rewarming injury and its prevention by short-term reperfusion[J]. Hepatology, 2000, 32(2): 289-296.
11	Uemura T, Randall HB, Sanchez EQ, et al. Liver retransplantation for primary nonfunction: analysis of a 20-year single-center experience[J]. Liver Transpl, 2007, 13(2): 227-233.
12	Belzer FO, Ashby BS, Gulyassy PF, et al. Successful seventeen-hour preservation and transplantation of human-cadaver kidney[J]. N Engl J Med, 1968, 278(11): 608-610.
13	Vekemans K, Liu Q, Pirenne J, et al. Artificial circulation of the liver: machine perfusion as a preservation method in liver transplantation[J]. Anat Rec (Hoboken), 2008, 291(6): 735-740.
14	Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation[J]. Nature, 2018, 557 (7703): 50-56.
15	Brockmann J, Reddy S, Coussios C, et al. Normothermic perfusion: a new paradigm for organ preservation[J]. Ann Surg, 2009, 250(1): 1-6.
16	Jochmans I, Moers C, Smits JM, et al. Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death: a multicenter, randomized, controlled trial[J]. Ann Surg, 2010, 252(5): 756-764.
17	Fondevila C, Hessheimer AJ, Maathuis MH, et al. Hypothermic oxygenated machine perfusion in porcine donation after circulatory determination of death liver transplant[J]. Transplantation, 2012. 94(1): 22-29.
18	Jamieson RW, Friend PJ. Organ reperfusion and preservation[J]. Front Biosci, 2008，13: 221-235.
19	Schlegel A, Kron P, Dutkowski P. Hypothermic machine perfusion in liver transplantation[J]. Curr Opin Organ Transplant, 2016, 21(3): 308-314.
20	de Meijer VE, Fujiyoshi M, Porte RJ. Ex situ machine perfusion strategies in liver transplantation[J]. J Hepatol, 2019, 70(1): 203-205.
21	Henry SD, Nachber E, Tulipan J, et a1. Hypothemlic machine preservation reduces nlolecular nlarkers of ischemia/repeffusion injury in human liver transplantation[J]. Am J Transplant, 2012, 12(9): 2477-2486.
22	Compagnon P, Levesque E, Hentati H, et al. An oxygenated and transportable machine perfusion system fully rescues liver grafts exposed to lethal ischemic damage in a pig model of DCD liver transplantation[J]. Transplantation, 2017, 101(7): e205-e213.
23	Guarrera JV, Henry SD, Samstein B, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series[J]. Am J Transplant, 2010, 10(2): 372-381.
24	Guarrera JV, Henry SD, Samstein B, et al. Hypothermic machine preservation facilitates successful transplantation of "orphan" extended criteria donor livers[J]. Am J Transplant, 2015, 15(1): 161-169.
25	Zhang Y, Zhang Y, Zhang M, et al. Hypothermic machine perfusion reduces the incidences of early allograft dysfunction and biliary complications and improves 1-year graft survival after human liver transplantation: A meta-analysis[J]. Medicine (Baltimore), 2019, 98(23): e16033.
26	Kron P, Schlegel A, Mancina L, et al. Hypothermic oxygenated perfusion (HOPE) for fatty liver grafts in rats and humans[J]. J Hepatol, 2017，68(1): 82-91.
27	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.
28	Van Rijn R, Karimian N, Matton APM, et al. First clinical series of end-ischemic hypothermic oxygenated machine perfusion via hepatic artery and portal vein in donation after circulatory death liver transplantation[J]. Transplantation, 2015, 99(Supp l): 86.
29	van Rijn R, Karimian N, Matton APM, et al. Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death[J]. Br J Surg, 2017, 104(7): 907-917.
30	van Rijn R, van Leeuwen OB, Matton APM, et al. Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers[J]. Liver Transpl, 2018, 24(5): 655-664.
31	Dutkowski P, Schlegel A, de Oliveira M, et al. HOPE for human liver grafts obtained from donors after cardiac death[J]. J Hepatol, 2014, 60(4): 765-772.
32	Fontes P, Lopez R, van der Plaats A, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions[J]. Am J Transplant, 2015, 15(2): 381-394.
33	Bruinsma BG, Yeh H, Ozer S, et al. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation[J]. Am J Transplant, 2014, 14(6): 1400-1409.
34	Ravikumar R, Jassem W, Mergental H, et al. Liver transplantation after ex vivo normothermic machine preservation: a phase 1 (first-in-man) clinical trial[J]. Am J Transplant, 2016, 16(6): 1779-1787.
35	Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation[J]. Nature, 2018, 557(7703): 50-56.
36	Bral M, Gala-Lopez B, Bigam D, et al. Preliminary single-center Canadian experience of human normothermic ex vivo liver perfusion: results of a clinical trial[J]. Am J Transplant, 2017, 17(4): 1071-1080.
37	Bral M, Dajani K, Leon Izquierdo D, et al. A back-to-base experience of human normothermic ex situ liver perfusion: Does the chill kill？[J]. Liver Transpl, 2019, 25(6): 848-858.
38	Attia M, Silva MA, Mirza DF. The marginal liver donor-an update[J]. Transpl Int, 2008, 21(8): 713-724.
39	Verhoeven CJ, Farid WR, de Jonge J, et al. Biomarkers to assess graft quality during conventional and machine preservation in liver transplantation[J]. J Hepatol, 2014, 61(3): 672-684.
40	Watson CJ, Kosmoliaptis V, Pley C, et al. Observations on the ex situ perfusion of livers for transplantation[J]. Am J Transplant, 2018, 18(8): 2005-2020.
41	Guarrera JV, Henry SD, Chen SW, et al. Hypothermic machine preservation attenuates ischemia/reperfusion markers after liver transplantation: preliminary results[J]. J Surg Res, 2011, 167(2): e365-e373.
42	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.
43	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.
44	Eshmuminov D, Becker D, Bautista Borrego L, et al. An integrated perfusion machine preserves injured human livers for 1 week[J]. Nat Biotechnol, 2020, 38(2): 189-198.
45	Bessems M, Doorschodt BM, Kolkert JL, et al. Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation[J]. Liver Transpl, 2007, 13(4): 497-504.
46	Vairetti M, Ferrigno A, Carlucci F, et al. Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase？[J]. Liver Transpl, 2009, 15(1): 20-29.
47	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.
48	Boteon YL, Attard J, Boteon APCS, et al. Manipulation of lipid metabolism during normothermic machine perfusion: effect of defatting therapies on donor liver functional recovery[J]. Liver Transpl, 2019, 25(7): 1007-1022.
49	Bishawi M, Roan JN, Milano CA, et al. A normothermic ex vivo organ perfusion delivery method for cardiac transplantation gene therapy[J]. Sci Rep, 2019, 9(1): 8029.
50	Machuca TN, Cypel M, Bonato R, et al. Safety and efficacy of ex vivo donor lung adenoviral IL-10 gene therapy in a large animal lung transplant survival model[J]. Hum Gene Ther, 2017，28: 757-765.
51	Ichim TE, Li MU, Qian H, et al. RNA interference: a potent tool for gene-specific therapeutics[J]. Am J Transplant, 2004, 4(8): 1227-1236.
52	Gillooly AR, Perry J, Martins PN. First report of siRNA uptake (for RNA Interference) during ex vivo hypothermic and normothermic liver machine perfusion [J]. Transplantation, 2019, 103(3): e56-e57.
53	Goldaracena N, Spetzler VN, Echeverri J, et al. Inducing hepatitis C virus resistance after pig liver transplantation-a proof of concept of liver graft modification using warm ex vivo perfusion[J]. Am J Transplant, 2017, 17(4): 970-978.
54	Pickar-Oliver A, Gersbach CA. The next generation of CRISPR-Cas technologies and applications[J]. Nat Rev Mol Cell Biol, 2019, 20(8): 490-507.
55	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.

[1]	Kunhe Li, Mengjia Kou, Liting Kuang. Risk factors and prediction model of reintubation after liver transplantation [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(05): 366-371.
[2]	Branch of Organ Transplant of Chinese Medical Association, Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Shanghai Pharmaceutical Profession Association. Expert Consensus on the Use of Mycophenolic Acid in Chinese Liver and Kidney Transplant Recipients (2023 edition) [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(05): 257-272.
[3]	Wenqing Lu, Xinyi Chen, Xuefei Ren. Investigation on the quality of life after liver transplantation in children with genetic metabolic diseases [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(05): 287-292.
[4]	Tieyan Fan, Jun Li, Hong Chen. Diagnosis and treatment experience of new onset viral hepatitis E after liver transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(05): 293-296.
[5]	Shuo Chen, Feng Chen, Fei Cheng, Jie Xiang. Pancreas infarction after liver transplantation for glycogen storage disease type Ⅰ complicated with pancreatitis: a case report [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(05): 300-302.
[6]	Penghao Tang, Wu Zhang. Progress in mechanism research about intestinal microecology with perioperative complications of liver transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(05): 303-307.
[7]	Committee of Health Management for Organ Transplant Recipient, China Organ Transplantation Development Foundation, Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Branch of Organ Transplant of Chinese Medical Association, National Center for Healthcare Quality Management in Liver Transplant. Chinese expert consensus on clinical application of inhibitors of mammalian target of rapamycin in liver transplant recipients (2023 edition) [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(04): 193-204.
[8]	Lina Zhu, Zizhen Yang, Di Zhang, Yong Zhang, Jinzhen Cai, Jianhong Wang. The application value of contrast-enhanced ultrasound in the diagnosis of hepatic artery complications after liver transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(04): 240-245.
[9]	Ye Xu, Jing Li, Ranjia Liu, Chen Pan, Mingxing Guo, Xiangli Cui. Analysis of the use of immunosuppressants after liver transplantation in 95 hospitals in China during 2017-2021 [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(03): 134-139.
[10]	Qing Yan, Ying Liu, Feiwen Deng, Huanwei Chen. Effect of microvascular invasion on survival and prognosis of liver transplantation recipients with liver cancer [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(06): 624-629.
[11]	Mei Liao, Hongjun Zhang, Jieyang Jin, Yan Lyu, Jie Ren. Diagnostic value of bedside contrast-enhanced ultrasound for early hepatic artery thrombosis after liver transplantation [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(06): 630-634.
[12]	Binglin Li, Shaocheng Lyu, Fei Pan, Tao Jiang, Hua Fan, Jiantao Kou, Qiang He, Ren Lang. Correlation analysis between pathogenic bacteria of donor liver perfusion fluid and early infection after liver transplantation [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(06): 656-660.
[13]	Lei Lyu, Xiao Feng, Kaiming He, Kaining Zeng, Qing Yang, Haijin Lyu, Huimin Yi, Shuhong Yi, Yang Yang, Binsheng Fu. Value of revised King's score in evaluation of live transplantation timing for children with acute liver failure due to Wilson's disease and literature review [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(06): 661-668.
[14]	Menglong Wang. Significance of biological characteristics in liver transplantation for HCC [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(05): 490-494.
[15]	Xiaodong Wang, Kai Wang, Zhao Ge. Research progress of computer vision in improvement of therapeutic effect of liver transplantation for liver cancer [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(04): 361-366.

Please choose a citation manager

Content to export