Ex-vivo perfusion of livers for transplantation

• Research type

  Research Study

• Full title

  Establishing ex-vivo normothermic and hypothermic perfusion of livers for transplantation

• IRAS ID

  179433

• Contact name

  Rodrigo Figueiredo

• Contact email

  r.figueiredo@nhs.net

• Sponsor organisation

  Newcastle upon Tyne Hospitals NHS Foundation Trust

• Duration of Study in the UK

  5 years, 0 months, 1 days

• Research summary

  The transplant waiting list continues to grow, with significant mortality on the waiting list, leading to a growing drive to utilise livers from "marginal" donors, including those from donors after circulatory death (DCD). However, the outcomes from these organs are often inferior (DCD 82% 1 year survival versus >90% DBD). The consequences of the warm ischaemic injury, together with unfavourable haemdynamics during the agonal phase, result in a reluctance to use livers from these donors. In 2012/13 only 27% of livers from DCD donors that met donation criteria were actually transplanted (83% DBD). These unused organs could be an opportunity to increase transplantation activity and reduce the number of deaths on the waiting list.

  Various liver perfusion devices are available (OrganAssist, Transmedics, OrganOx, Medtronic), this project aims to evaluate the ability of this technology to increase the number of transplantable organs. There remains debate over which temperature (hypothermic 10°C or normothermic 37°C) is the best to perform these functions:

  Assessment of marginal livers
  Reconditioning of DCD livers
  Platform for drug delivery

  We intend to perform ex-vivo perfusion using 24 “discarded” livers to assess the response to hypothermic perfusion (n=6), normothermic perfusion (n=6), hypothermic drug delivery (n=6) and normothermic drug delivery (n=6). We are looking to understand the cellular/molecular processes occurring during perfusion that are responsible for “reconditioning”. We will be taking biopsies, photographs, perfusate and blood samples at the beginning, middle and end of perfusion. These samples will be analysed for biochemistry, haematology, histology, immunohistochemistry, RNA assessment and profiling, genotyping and fat assessment (macro/microvesicular fat content). On the basis of these profiles established in the first 12 organ perfusions we will select interventions (pharmacological, biological or physical) to try and improve the “quality” of the liver. Potential candidates include endothelin receptor antagonists, anti-sense oligonulceotides, amino acids, mesenchymal stem cells or antibodies (monoclonal/polyclonal).

• REC name

  East Midlands - Nottingham 2 Research Ethics Committee

• REC reference

  15/EM/0285

• Date of REC Opinion

  23 Jun 2015

• REC opinion

  Favourable Opinion