Transplantation of High-risk Donor Livers After Ex Situ Resuscitation and Assessment Using Combined Hypo- and Normothermic Machine Perfusion: A Prospective Clinical Trial

Ann Surg. 2019 Nov;270(5):906-914. doi: 10.1097/SLA.0000000000003540.


Objective: The aim of this study was to evaluate sequential hypothermic and normothermic machine perfusion (NMP) as a tool to resuscitate and assess viability of initially declined donor livers to enable safe transplantation.

Summary background data: Machine perfusion is increasingly used to resuscitate and test the function of donor livers. Although (dual) hypothermic oxygenated machine perfusion ([D]HOPE) resuscitates livers after cold storage, NMP enables assessment of hepatobiliary function.

Methods: In a prospective clinical trial, nationwide declined livers were subjected to ex situ NMP (viability assessment phase), preceded by 1-hour DHOPE (resuscitation phase) and 1 hour of controlled oxygenated rewarming (COR), using a perfusion fluid containing an hemoglobin-based oxygen carrier. During the first 2.5 hours of NMP, hepatobiliary viability was assessed, using predefined criteria: perfusate lactate <1.7 mmol/L, pH 7.35 to 7.45, bile production >10 mL, and bile pH >7.45. Livers meeting all criteria were accepted for transplantation. Primary endpoint was 3-month graft survival.

Results: Sixteen livers underwent DHOPE-COR-NMP. All livers were from donors after circulatory death, with median age of 63 (range 42-82) years and median Eurotransplant donor risk index of 2.82. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 livers bile pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, with 100% patient and graft survival at 3 and 6 months. Introduction of DHOPE-COR-NMP increased the number of deceased donor liver transplants by 20%.

Conclusions: Sequential DHOPE-COR-NMP enabled resuscitation and safe selection of initially declined high-risk donor livers, thereby increasing the number of transplantable livers by 20%.

Trial registration:; NTR5972.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cold Ischemia / methods*
  • Donor Selection
  • Female
  • Graft Rejection
  • Graft Survival
  • Hepatectomy / methods
  • Humans
  • Kaplan-Meier Estimate
  • Liver Transplantation / adverse effects
  • Liver Transplantation / methods*
  • Living Donors
  • Male
  • Middle Aged
  • Organ Preservation / methods*
  • Patient Safety
  • Perfusion / methods
  • Prognosis
  • Prospective Studies
  • Reperfusion Injury / prevention & control*
  • Resuscitation / methods
  • Risk Assessment
  • Statistics, Nonparametric
  • Survival Analysis
  • Tissue and Organ Procurement*
  • Treatment Outcome
  • Warm Ischemia / methods*