Frontiers of Medicine

, Volume 10, Issue 4, pp 451–464 | Cite as

Machine perfusion versus cold storage of livers: a meta-analysis

  • Sushun Liu
  • Qing Pang
  • Jingyao Zhang
  • Mimi Zhai
  • Sinan Liu
  • Chang Liu
Research Article


Different organ preservation methods are key factors influencing the results of liver transplantation. In this study, the outcomes of experimental models receiving donation after cardiac death (DCD) livers preserved through machine perfusion (MP) or static cold storage (CS) were compared by conducting a meta-analysis. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to compare pooled data from two animal species. Twenty-four studies involving MP preservation were included in the meta-analysis. Compared with CS preservation, MP can reduce the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and hyaluronic acid (HA) and the changes in liver weight. By contrast, MP can enhance bile production and portal vein flow (PVF). Alkaline phosphatase (ALP) levels and histological changes significantly differed between the two preservation methods. In conclusion, MP of DCD livers is superior to CS in experimental animals.


machine perfusion cold storage DCD meta-analysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Matsuno N, Kobayashi E. Challenges in machine perfusion preservation for liver grafts from donation after circulatory death. Transplant Res 2013; 2(1): 19CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Compagnon P, Clément B, Campion JP, Boudjema K. Effects of hypothermic machine perfusion on rat liver function depending on the route of perfusion. Transplantation 2001; 72(4): 606–614CrossRefPubMedGoogle Scholar
  3. 3.
    Deng R, Gu G, Wang D, Tai Q, Wu L, Ju W, Zhu X, Guo Z, He X. Machine perfusion versus cold storage of kidneys derived from donation after cardiac death: a meta-analysis. PLoS ONE 2013; 8(3): e56368CrossRefGoogle Scholar
  4. 4.
    St Peter SD, Imber CJ, Friend PJ. Liver and kidney preservation by perfusion. Lancet 2002; 359(9306): 604–613CrossRefPubMedGoogle Scholar
  5. 5.
    Clavien PA, Harvey PR, Strasberg SM. Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies. Transplantation 1992; 53(5): 957–978PubMedGoogle Scholar
  6. 6.
    Kootstra G, van Heurn E. Non-heartbeating donation of kidneys for transplantation. Nat Clin Pract Nephrol 2007; 3(3): 154–163CrossRefPubMedGoogle Scholar
  7. 7.
    Kwiatkowski A, Wszola M, Kosieradzki M, Danielewicz R, Ostrowski K, Domagala P, Lisik W, Nosek R, Fesolowicz S, Trzebicki J, Durlik M, Paczek L, Chmura A, Rowinski W. Machine perfusion preservation improves renal allograft survival. Am J Transplant 2007; 7(8): 1942–1947CrossRefPubMedGoogle Scholar
  8. 8.
    Moers C, Smits JM, Maathuis MH, Treckmann J, van Gelder F, Napieralski BP, van Kasterop-Kutz M, van der Heide JJ, Squifflet JP, van Heurn E, Kirste GR, Rahmel A, Leuvenink HG, Paul A, Pirenne J, Ploeg RJ. Machine perfusion or cold storage in deceaseddonor kidney transplantation. N Engl J Med 2009; 360(1): 7–19CrossRefPubMedGoogle Scholar
  9. 9.
    Lanir A, Clouse ME, Lee RG. Liver preservation for transplant. Evaluation of hepatic energy metabolism by 31P NMR. Transplantation 1987; 43(6): 786–790PubMedGoogle Scholar
  10. 10.
    Fuller BJ, Busza AL, Proctor E. Possible resuscitation of liver function by hypothermic reperfusion in vitro after prolonged (24-hour) cold preservation—a 31P NMR study. Transplantation 1990; 50(3): 511–513CrossRefPubMedGoogle Scholar
  11. 11.
    Lockett CJ, Fuller BJ, Busza AL, Proctor E. Hypothermic perfusion preservation of liver: the role of phosphate in stimulating ATP synthesis studied by 31P NMR. Transpl Int 1995; 8(6): 440–445CrossRefPubMedGoogle Scholar
  12. 12.
    Kim JS, Boudjema K, D’Alessandro A, Southard JH. Machine perfusion of the liver: maintenance of mitochondrial function after 48-hour preservation. Transplant Proc 1997; 29(8): 3452–3454CrossRefPubMedGoogle Scholar
  13. 13.
    Balfoussia D, Yerrakalva D, Hamaoui K, Papalois V. Advances in machine perfusion graft viability assessment in kidney, liver, pancreas, lung, and heart transplant. Exp Clin Transplant 2012; 10(2): 87–100CrossRefPubMedGoogle Scholar
  14. 14.
    Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 2010; 8(6): e1000412CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, Lo EH; STAIR Group. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009; 40(6): 2244–2250CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Iwamoto H, Matsuno N, Narumi Y, Uchiyama M, Kozaki K, Degawa H, Hama K, Kikuchi K, Takeuchi H, Kozaki M, Nagao T. Beneficial effect of machine perfusion preservation on liver transplantation from non-heart-beating donors. Transplant Proc 2000; 32(7): 1645–1646CrossRefPubMedGoogle Scholar
  17. 17.
    Imber CJ, St Peter SD, Lopez de Cenarruzabeitia I, Pigott D, James T, Taylor R, McGuire J, Hughes D, Butler A, Rees M, Friend PJ. Advantages of normothermic perfusion over cold storage in liver preservation. Transplantation 2002; 73(5): 701–709CrossRefPubMedGoogle Scholar
  18. 18.
    St Peter SD, Imber CJ, Lopez I, Hughes D, Friend PJ. Extended preservation of non-heart-beating donor livers with normothermic machine perfusion. Br J Surg 2002; 89(5): 609–616CrossRefPubMedGoogle Scholar
  19. 19.
    Jain S, Lee CY, Baicu S, Duncan H, Xu H, Jones JW, Clemens MG, Brassil J, Taylor MJ, Brockbank KG. Hepatic function in hypothermically stored porcine livers: comparison of hypothermic machine perfusion vs. cold storage. Transplant Proc 2005; 37(1): 340–341CrossRefPubMedGoogle Scholar
  20. 20.
    Guarrera JV, Estevez J, Boykin J, Boyce R, Rashid J, Sun S, Arrington B. Hypothermic machine perfusion of liver grafts for transplantation: technical development in human discard and miniature swine models. Transplant Proc 2005; 37(1): 323–325CrossRefPubMedGoogle Scholar
  21. 21.
    Bessems M, Doorschodt BM, Dinant S, de Graaf W, van Gulik TM. Machine perfusion preservation of the pig liver using a new preservation solution, polysol. Transplant Proc 2006; 38(5): 1238–1242CrossRefPubMedGoogle Scholar
  22. 22.
    Vekemans K, Liu Q, Brassil J, Komuta M, Pirenne J, Monbaliu D. Influence of flow and addition of oxygen during porcine liver hypothermic machine perfusion. Transplant Proc 2007; 39(8): 2647–2651CrossRefPubMedGoogle Scholar
  23. 23.
    Monbaliu D, Heedfeld V, Liu Q, Wylin T, van Pelt J, Vekemans K, Pirenne J. Hypothermic machine perfusion of the liver: is it more complex than for the kidney? Transplant Proc 2011; 43(9): 3445–3450CrossRefPubMedGoogle Scholar
  24. 24.
    Fondevila C, Hessheimer AJ, Maathuis MH, Muñoz J, Taurá P, Calatayud D, Leuvenink H, Rimola A, García-Valdecasas JC, Ploeg RJ. Hypothermic oxygenated machine perfusion in porcine donation after circulatory determination of death liver transplant. Transplantation 2012; 94(1): 22–29CrossRefPubMedGoogle Scholar
  25. 25.
    Nassar A, Liu Q, Farias K, D’Amico G, Tom C, Grady P, Bennett A, Diago Uso T, Eghtesad B, Kelly D, Fung J, Abu-Elmagd K, Miller C, Quintini C. Ex vivo normothermic machine perfusion is safe, simple, and reliable: results from a large animal model. Surg Innov 2015; 22(1): 61–69CrossRefPubMedGoogle Scholar
  26. 26.
    Op den Dries S, Sutton ME, Karimian N, de Boer MT, Wiersema-Buist J, Gouw AS, Leuvenink HG, Lisman T, Porte RJ. Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. PLoS ONE 2014; 9(2): e88521CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lee CY, Zhang JX, Jones JW, Southard JH, Clemens MG. Functional recovery of preserved livers following warm ischemia: improvement by machine perfusion preservation. Transplantation 2002; 74(7): 944–951CrossRefPubMedGoogle Scholar
  28. 28.
    Lee CY, Jain S, Duncan HM, Zhang JX, Jones JW, Southard JH, Clemens MG. Survival transplantation of preserved non-heartbeating donor rat livers: preservation by hypothermic machine perfusion. Transplantation 2003; 76(10): 1432–1436CrossRefPubMedGoogle Scholar
  29. 29.
    Xu H, Lee CY, Clemens MG, Zhang JX. Pronlonged hypothermic machine perfusion preserves hepatocellular function but potentiates endothelial cell dysfunction in rat livers. Transplantation 2004; 77(11): 1676–1682CrossRefPubMedGoogle Scholar
  30. 30.
    Bessems M, Doorschodt BM, van Marle J, Vreeling H, Meijer AJ, van Gulik TM. Improved machine perfusion preservation of the non-heart-beating donor rat liver using Polysol: a new machine perfusion preservation solution. Liver Transpl 2005; 11(11): 1379–1388CrossRefPubMedGoogle Scholar
  31. 31.
    Bessems M, Doorschodt BM, Kolkert JL, Vetelainen RL, van Vliet AK, Vreeling H, van Marle J, van Gulik TM. Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. Liver Transpl 2007; 13(4): 497–504CrossRefPubMedGoogle Scholar
  32. 32.
    Vairetti M, Ferrigno A, Rizzo V, Richelmi P, Boncompagni E, Neri D, Freitas I, Cillo U. Subnormothermic machine perfusion protects against rat liver preservation injury: a comparative evaluation with conventional cold storage. Transplant Proc 2007; 39(6): 1765–1767CrossRefPubMedGoogle Scholar
  33. 33.
    Vairetti M, Ferrigno A, Rizzo V, Boncompagni E, Carraro A, Gringeri E, Milanesi G, Barni S, Freitas I, Cillo U. Correlation between the liver temperature employed during machine perfusion and reperfusion damage: role of Ca2+. Liver Transpl 2008; 14(4): 494–503CrossRefPubMedGoogle Scholar
  34. 34.
    Ferrigno A, Carlucci F, Tabucchi A, Tommassini V, Rizzo V, Richelmi P, Gringeri E, Neri D, Boncompagni E, Freitas I, Cillo U, Vairetti M. Different susceptibility of liver grafts from lean and obese Zucker rats to preservation injury. Cryobiology 2009; 59(3): 327–334CrossRefPubMedGoogle Scholar
  35. 35.
    Vairetti M, Ferrigno A, Carlucci F, Tabucchi A, Rizzo V, Boncompagni E, Neri D, Gringeri E, Freitas I, Cillo U. Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase? Liver Transpl 2009; 15(1): 20–29CrossRefGoogle Scholar
  36. 36.
    Olschewski P, Gass P, Ariyakhagorn V, Jasse K, Hunold G, Menzel M, Schöning W, Schmitz V, Neuhaus P, Puhl G. The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers. Cryobiology 2010; 60(3): 337–343CrossRefPubMedGoogle Scholar
  37. 37.
    Boncompagni E, Gini E, Ferrigno A, Milanesi G, Gringeri E, Barni S, Cillo U, Vairetti M, Freitas I. Decreased apoptosis in fatty livers submitted to subnormothermic machine-perfusion respect to cold storage. Eur J Histochem 2011; 55(4): e40CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Ferrigno A, Rizzo V, Boncompagni E, Bianchi A, Gringeri E, Neri D, Richelmi P, Freitas I, Cillo U, Vairetti M. Machine perfusion at 20 °C reduces preservation damage to livers from non-heart beating donors. Cryobiology 2011; 62(2): 152–158CrossRefPubMedGoogle Scholar
  39. 39.
    Carnevale ME, Balaban CL, Guibert EE, Bottai H, Rodriguez JV. Hypothermic machine perfusion versus cold storage in the rescuing of livers from non-heart-beating donor rats. Artif Organs 2013; 37(11): 985–991CrossRefPubMedGoogle Scholar
  40. 40.
    Lim WY, Messow CM, Berry C. Cyclosporin variably and inconsistently reduces infarct size in experimental models of reperfused myocardial infarction: a systematic review and metaanalysis. Br J Pharmacol 2012; 165(7): 2034–2043CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Navarro AP, Asher J, Sohrabi S, Reddy M, Stamp S, Carter N, Talbot D. Peritoneal cooling may provide improved protection for uncontrolled donors after cardiac death: an exploratory porcine study. Am J Transplant 2009; 9(6): 1317–1323CrossRefPubMedGoogle Scholar
  42. 42.
    Dutkowski P, Graf R, Clavien PA. Rescue of the cold preserved rat liver by hypothermic oxygenated machine perfusion. Am J Transplant 2006; 6(5 Pt 1): 903–912CrossRefPubMedGoogle Scholar
  43. 43.
    Giannone FA, Treré D, Domenicali M, Grattagliano I, Baracca A, Sgarbi G, Maggioli C, Longobardi P, Solaini G, Derenzini M, Bernardi M, Caraceni P. An innovative hyperbaric hypothermic machine perfusion protects the liver from experimental preservation injury. Sci World J 2012; 2012: 573410CrossRefGoogle Scholar
  44. 44.
    Tan XD, Egami H, Wang FS, Ogawa M. Protective effect of exogenous adenosine triphosphate on hypothermically preserved rat liver. World J Gastroenterol 2004; 10(6): 871–874CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Tolboom H, Milwid JM, Izamis ML, Uygun K, Berthiaume F, Yarmush ML. Sequential cold storage and normothermic perfusion of the ischemic rat liver. Transplant Proc 2008; 40(5): 1306–1309CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6(7): e1000097CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Cantafio AW, Dick AA, Halldorson JB, Bakthavatsalam R, Reyes JD, Perkins JD. Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion. Clin Transplant 2011; 25(5): E530–E540CrossRefPubMedGoogle Scholar
  48. 48.
    Wight JP, Chilcott JB, Holmes MW, Brewer N. Pulsatile machine perfusion vs.cold storage of kidneys for transplantation: a rapid and systematic review. Clin Transplant 2003; 17(4): 293–307CrossRefPubMedGoogle Scholar
  49. 49.
    Guarrera JV, Henry SD, Samstein B, Odeh-Ramadan R, Kinkhabwala M, Goldstein MJ, Ratner LE, Renz JF, Lee HT, Brown RS Jr, Emond JC. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant 2010; 10(2): 372–381CrossRefPubMedGoogle Scholar
  50. 50.
    Guarrera JV. Assist devices: machine preservation of extended criteria donors. Liver Transpl 2012; 18(Suppl 2): S31–S33CrossRefPubMedGoogle Scholar
  51. 51.
    Guarrera JV, Henry SD, Chen SW, Brown T, Nachber E, Arrington B, Boykin J, Samstein B, Brown RS, Emond JC, Lee HT. Hypothermic machine preservation attenuates ischemia/reperfusion markers after liver transplantation: preliminary results. J Surg Res 2011; 167(2): e365–e373CrossRefPubMedGoogle Scholar
  52. 52.
    Guarrera JV, Henry SD, Samstein B, Reznik E, Musat C, Lukose TI, Ratner LE, Brown RS Jr, Kato T, Emond JC. Hypothermic machine preservation facilitates successful transplantation of “orphan” extended criteria donor livers. Am J Transplant 2015; 15(1): 161–169CrossRefPubMedGoogle Scholar
  53. 53.
    Bae C, Henry SD, Guarrera JV. Is extracorporeal hypothermic machine perfusion of the liver better than the ‘good old icebox’? Curr Opin Organ Transplant 2012; 17(2): 137–142CrossRefPubMedGoogle Scholar
  54. 54.
    Buis CI, Hoekstra H, Verdonk RC, Porte RJ. Causes and consequences of ischemic-type biliary lesions after liver transplantation. J Hepatobiliary Pancreat Surg 2006; 13(6): 517–524CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Sushun Liu
    • 1
  • Qing Pang
    • 1
  • Jingyao Zhang
    • 1
  • Mimi Zhai
    • 1
  • Sinan Liu
    • 1
  • Chang Liu
    • 1
  1. 1.Department of Hepatobiliary Surgery, The First Affiliated Hospital, School of MedicineXi’an Jiaotong UniversityXi’anChina

Personalised recommendations