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Use of machine perfusion in livers showing steatosis prior to transplantation: a systematic review

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Abstract

Background

The role of machine perfusion (MP) in the evaluation of liver grafts with macrovesicular steatosis (MaS) remains ill-defined as only a limited number of studies has been reported. The objective of the current study was to provide a systematic review to evaluate the role of MP in the setting of MaS livers.

Methods

A systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Eligible articles published up to April 2019 were included using the MEDLINE, Scopus, and Google Scholar databases.

Results

Among the 422 articles screened, only 16 papers met the inclusion criteria. A total of 54 cases of MP use before liver transplantation were included. Sixteen (29.6%) grafts were from donors after circulatory death. In 22 (40.7%) cases, hypothermic machine perfusion was performed. Normothermic machine perfusion was done in the remaining 32 (59.3%) cases. According to the histological results of the donor core biopsy, a MaS value < 30% was observed in 41 (75.9%) cases, whereas 13 (24.1%) patients had moderate-to-severe (≥ 30%) MaS. Following categorization of the pooled population according to the presence of moderate-to-severe (≥ 30%) MaS in the donor graft, no differences were noted in terms of post-transplant death or severe complications following MP. There was no correlation between the proportion of MaS in the donor graft relative to post-transplant peak ALT among patients treated with MP. Among the entire pooled cohort, there was also no correlation between MaS values and ALT peak (R = 0.13; P = 0.42).

Conclusions

MP appears to be feasible and safe in MaS livers. Experience to date has been very limited, and the benefit of MP remains not determined. Prospective studies will need to define better the potential effect of “defatting” drugs used during the perfusion process on MaS.

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References

  1. Feng S, Lai JC (2014) Expanded criteria donors. Clin Liver Dis 18:633–649

    PubMed  PubMed Central  Google Scholar 

  2. Ghinolfi D, Lai Q, Pezzati D, De Simone P, Rreka E, Filipponi F (2018) Use of elderly donors in liver transplantation: a paired-match analysis at a single center. Ann Surg 268:325–331

    PubMed  Google Scholar 

  3. Chu MJ, Dare AJ, Phillips AR, Bartlett AS (2015) Donor hepatic steatosis and outcome after liver transplantation: a systematic review. J Gastrointest Surg 19:1713–1724

    PubMed  Google Scholar 

  4. de Graaf EL, Kench J, Dilworth P, Shackel NA, Strasser SI, Joseph D et al (2012) Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index. J Gastroenterol Hepatol 27:540–546

    PubMed  Google Scholar 

  5. Lee DD, Croome KP, Shalev JA, Musto KR, Sharma M, Keaveny AP et al (2016) Early allograft dysfunction after liver transplantation: an intermediate outcome measure for targeted improvements. Ann Hepatol 15:53–60

    PubMed  Google Scholar 

  6. Lattanzi B, Lai Q, Guglielmo N, Giannelli V, Merli M, Giusto M et al (2013) Graft macrosteatosis and time of T-tube removal as risk factors for biliary strictures after liver transplantation. Clin Transplant 27:E332–E338

    PubMed  Google Scholar 

  7. Shin YH, Ko JS, Kim GS, Gwak MS, Sim WS, Lee AR et al (2012) Impact of hepatic macrovesicular and microvesicular steatosis on the postoperative liver functions after right hepatectomy in living donors. Transplant Proc 44:512–515

    CAS  PubMed  Google Scholar 

  8. Sharkey FE, Lytvak I, Prihoda TJ, Speeg KV, Washburn WK, Halff GA (2011) High-grade microsteatosis and delay in hepatic function after orthotopic liver transplantation. Hum Pathol 42:1337–1342

    PubMed  Google Scholar 

  9. Westerkamp AC, de Boer MT, van den Berg AP, Gouw AS, Porte RJ (2015) Similar outcome after transplantation of moderate macrovesicular steatotic and nonsteatotic livers when the cold ischemia time is kept very short. Transpl Int 28:319–329

    CAS  PubMed  Google Scholar 

  10. Spitzer AL, Lao OB, Dick AA, Bakthavatsalam R, Halldorson JB, Yeh MM et al (2010) The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl 16:874–884

    PubMed  Google Scholar 

  11. Nasralla D, Coussios CC, Mergental H, Akhtar MZ, Butler AJ, Ceresa CDL (2018) Consortium for organ preservation in Europe. a randomized trial of normothermic preservation in liver transplantation. Nature 557:50–56

    CAS  PubMed  Google Scholar 

  12. Lai Q, Melandro F, Rossi M, Ruberto F, Pugliese F, Mennini G (2018) Role of perfusion machines in the setting of clinical liver transplantation: a qualitative systematic review. Clin Transplant 32:e13310

    PubMed  Google Scholar 

  13. Boteon YL, Boteon APCS, Attard J, Mergental H, Mirza DF, Bhogal RH et al (2018) Ex situ machine perfusion as a tool to recondition steatotic donor livers: troublesome features of fatty livers and the role of defatting therapies. A systematic review. Am J Transplant 18:2384–2399

    PubMed  Google Scholar 

  14. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162:777–784

    PubMed  Google Scholar 

  15. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in metaanalyses. Eur J Epidemiol 25:603–605

    PubMed  Google Scholar 

  16. Guarrera JV, Henry SD, Samstein B, Reznik E, Musat C, Lukose TI et al (2015) Hypothermic machine preservation facilitates successful transplantation of "orphan" extended criteria donor livers. Am J Transplant 15:161–169

    CAS  PubMed  Google Scholar 

  17. Ravikumar R, Jassem W, Mergental H, Heaton N, Mirza D, Perera MT et al (2016) Liver transplantation after ex vivo normothermic machine preservation: a phase 1 (first-in-man) clinical trial. Am J Transplant 16:1779–1787

    CAS  PubMed  Google Scholar 

  18. De Carlis L, De Carlis R, Lauterio A, Di Sandro S, Ferla F, Zanierato M (2016) Sequential use of normothermic regional perfusion and hypothermic machine perfusion in donation after cardiac death liver transplantation with extended warm ischemia time. Transplantation 100:e101–e102

    PubMed  Google Scholar 

  19. Mergental H, Perera MT, Laing RW, Muiesan P, Isaac JR, Smith A et al (2016) Transplantation of declined liver allografts following normothermic ex-situ evaluation. Am J Transplant 16:3235–3245

    CAS  PubMed  Google Scholar 

  20. Kron P, Schlegel A, Mancina L, Clavien PA, Dutkowski P (2018) Hypothermic oxygenated perfusion (HOPE) for fatty liver grafts in rats and humans. J Hepatol 68:82–91

    CAS  Google Scholar 

  21. Pezzati D, Ghinolfi D, Balzano E, De Simone P, Coletti L, Roffi N et al (2017) Salvage of an octogenarian liver graft using normothermic perfusion: a case report. Transplant Proc 49:726–728

    CAS  PubMed  Google Scholar 

  22. Watson CJE, Kosmoliaptsis V, Randle LV, Gimson AE, Brais R, Klinck JR et al (2017) Normothermic perfusion in the assessment and preservation of declined livers before transplantation: hyperoxia and vasoplegia-important lessons from the first 12 cases. Transplantation 101:1084–1098

    PubMed  PubMed Central  Google Scholar 

  23. He X, Guo Z, Zhao Q, Ju W, Wang D, Wu L et al (2018) The first case of ischemia-free organ transplantation in humans: a proof of concept. Am J Transplant 18:737–744

    PubMed  Google Scholar 

  24. Patrono D, Lavezzo B, Molinaro L, Rizza G, Catalano G, Gonella F et al (2018) Hypothermic oxygenated machine perfusion for liver transplantation: an initial experience. Exp Clin Transplant 16:172–176

    PubMed  Google Scholar 

  25. Zhao Q, Huang S, Wang D, Zhang Z, Wu L, Yang L et al (2018) Does ischemia free liver procurement under normothermic perfusion benefit the outcome of liver transplantation? Ann Transplant 23:258–267

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ghinolfi D, Rreka E, De Tata V, Franzini M, Pezzati D, Fierabracci V, Masini M, Cacciatoinsilla A, Bindi ML, Marselli L, Mazzotti V, Morganti R, Marchetti P, Biancofiore G, Campani D, Paolicchi A, De Simone P (2019) Pilot, open, randomized, prospective trial for normothermic machine perfusion evaluation in liver transplantation from older donors. Liver Transpl 25:436–449

    PubMed  Google Scholar 

  27. Rayar M, Maillot B, Bergeat D, Camus C, Houssel-Debry P, Sulpice L, Meunier B, Boudjema K (2018) A preliminary clinical experience using hypothermic oxygenated machine perfusion for rapid recovery of octogenarian liver grafts. Prog Transplant 29:1526924818817072

    Google Scholar 

  28. Jassem W, Xystrakis E, Ghnewa YG, Yuksel M, Pop O, Martinez-Llordella M, Jabri Y, Huang X, Lozano JJ, Quaglia A, Sanchez-Fueyo A, Coussios CC, Rela M, Friend P, Heaton N, Ma Y (2018) Normothermic machine perfusion (NMP) inhibits proinflammatory responses in the liver and promotes regeneration. Hepatology. https://doi.org/10.1002/hep.30475[Epub ahead of print]

    Article  Google Scholar 

  29. Dondossola D, Lonati C, Zanella A, Maggioni M, Antonelli B, Reggiani P, Gatti S, Rossi G (2019) Preliminary experience with hypothermic oxygenated machine perfusion in an italian liver transplant center. Transplant Proc 51:111–116

    CAS  PubMed  Google Scholar 

  30. Bral M, Dajani K, Leon Izquierdo D, Bigam D, Kneteman N, Ceresa CDL, Friend PJ, Shapiro AMJ (2019) A 'Back-to-base' experience of human normothermic ex situ liver perfusion: does the chill kill? Liver Transpl. https://doi.org/10.1002/lt.25464[Epub ahead of print]

    Article  PubMed  Google Scholar 

  31. Manzia TM, Toti L, Quaranta C, Blasi F, Tisone G (2019) Liver transplantation with a normothermic machine preserved fatty nonagenarian liver: a case report. Int J Surg Case Rep 57:163–166

    PubMed  PubMed Central  Google Scholar 

  32. Seifalian AM, Piasecki C, Agarwal A, Davidson BR (1999) The effect of graded steatosis on flow in the hepatic parenchymal microcirculation. Transplantation 68:780–784

    CAS  PubMed  Google Scholar 

  33. Graham JA, Guarrera JV (2014) "Resuscitation" of marginal liver allografts for transplantation with machine perfusion technology. J Hepatol 61:418–431

    PubMed  Google Scholar 

  34. Ferrigno A, Carlucci F, Tabucchi A, Tommassini V, Rizzo V, Richelmi P et al (2009) Different susceptibility of liver grafts from lean and obese Zucker rats to preservation injury. Cryobiology 59:327–334

    CAS  PubMed  Google Scholar 

  35. Vairetti M, Ferrigno A, Carlucci F, Tabucchi A, Rizzo V, Boncompagni E et al (2009) Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase? Liver Transpl 15:20–29

    PubMed  Google Scholar 

  36. Boncompagni E, Gini E, Ferrigno A, Milanesi G, Gringeri E, Barni S et al (2011) Decreased apoptosis in fatty livers submitted to subnormothermic machine-perfusion respect to cold storage. Eur J Histochem 55:e40

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Okamura Y, Hata K, Tanaka H, Hirao H, Kubota T, Inamoto O et al (2017) Impact of subnormothermic machine perfusion preservation in severely steatotic rat livers: a detailed assessment in an isolated setting. Am J Transplant 17:1204–1215

    CAS  PubMed  Google Scholar 

  38. Tarantola E, Bertone V, Milanesi G, Gruppi C, Ferrigno A, Vairetti M et al (2014) Dipeptidylpeptidase-IV activity and expression reveal decreased damage to the intrahepatic biliary tree in fatty livers submitted to subnormothermic machine-perfusion respect to conventional cold storage. Eur J Histochem 58:2414

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Liu Q, Berendsen T, Izamis ML, Uygun B, Yarmush ML, Uygun K (2013) Perfusion defatting at subnormothermic temperatures in steatotic rat livers. Transplant Proc 45:3209–3213

    CAS  PubMed  Google Scholar 

  40. Croce AC, Ferrigno A, Bertone V, Piccolini VM, Berardo C, Di Pasqua LG et al (2017) Fatty liver oxidative events monitored by autofluorescence optical diagnosis: comparison between subnormothermic machine perfusion and conventional cold storage preservation. Hepatol Res 47:668–682

    CAS  PubMed  Google Scholar 

  41. Ferrigno A, Di Pasqua LG, Berardo C, Siciliano V, Rizzo V, Mannucci B et al (2017) Liver graft susceptibility during static cold storage and dynamic machine perfusion: DCD versus fatty livers. Int J Mol Sci 19:E109

    PubMed  Google Scholar 

  42. Bessems M, Doorschodt BM, Kolkert JL, Vetelainen RL, van Vliet AK, Vreeling H et al (2007) Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. Liver Transpl 13:497–504

    PubMed  Google Scholar 

  43. Monbaliu D, Liu Q, Libbrecht L, De Vos R, Vekemans K, Debbaut C et al (2012) Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: a proof-of-concept study using discarded human livers. Liver Transpl 18:1495–1507

    PubMed  Google Scholar 

  44. Beijert I, Mert S, Huang V, Karimian N, Geerts S, Hafiz EOA et al (2018) Endothelial dysfunction in steatotic human donor livers: a pilot study of the underlying mechanism during subnormothermic machine perfusion. Transplant Direct 4:e345

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Liu Q, Nassar A, Buccini L, Iuppa G, Soliman B, Pezzati D et al (2018) Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion. Liver Transpl 24:233–245

    PubMed  Google Scholar 

  46. Schlegel A, Muller X, Kalisvaart M, Muellhaupt B, Perera MTPR, Isaac JR, Clavien PA, Muiesan P, Dutkowski P (2019) Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation. J Hepatol 70:50–57

    CAS  PubMed  Google Scholar 

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Funding

The authors have not received any support for the present study.

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Author notes

  1. Quirino Lai and Franco Ruberto are equally contributed to the present work.

Authors and Affiliations

  1. Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    Quirino Lai & Massimo Rossi

  2. Department of Anaesthesiology, Critical Care Medicine and Pain Therapy, Sapienza University of Rome, Rome, Italy

    Franco Ruberto & Francesco Pugliese

  3. The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Timothy M. Pawlik

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  1. Quirino Lai
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  2. Franco Ruberto
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  4. Francesco Pugliese
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  5. Massimo Rossi
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Contributions

QL and FR contributed to conception and design of the study; QL and FR contributed to acquisition of data; QL and FR analyzed and interpreted the data; QL drafted the article; TMP, FP, and MR critically revised the manuscript; and all authors approved the final version.

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Correspondence to Quirino Lai.

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All procedures performed in the cited studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies involving animals performed by any of the authors.

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Lai, Q., Ruberto, F., Pawlik, T.M. et al. Use of machine perfusion in livers showing steatosis prior to transplantation: a systematic review. Updates Surg 72, 595–604 (2020). https://doi.org/10.1007/s13304-020-00797-4

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  • DOI: https://doi.org/10.1007/s13304-020-00797-4

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