Hypothermic oxygenated perfusion (HOPE) of human liver grafts before transplantation - A multicenter, randomized controlled trial

Ischemia-reperfusion injury is universal in organ transplantation and leads to
varying degrees of graft dysfunction. Despite this fact, the preservation
method in organ transplantation has been left unchanged for many years and
remains simple static cold storage. Given the scarce donor supply, an
increasing number of so called marginal or extended criteria donor organs have
been used for liver transplantation, grafts which were previously rarely
considered. In addition, allocation policy has changed in Switzerland, as in
many other countries, and livers are now distributed by the severity of the
recipient*s disease. In this context, the MELD system (Model for end stage
liver disease) is frequently used for allocation of livers. As a result,
transplant candidates present sicker, with higher MELD scores, at the time of
transplant and the risk of graft dysfunction or even failure due to reperfusion
injury is high after the use of marginal livers in sick recipients.
Machine liver perfusion techniques have been improved during the past decade to
decrease reperfusion injury, and a number of promising results show beneficial
effects in various animal transplant models by either normothermic or
hypothermic oxygenated continuous liver perfusion. These techniques generally
require machine liver perfusion immediately after organ procurement. Hence
continuous perfusion has several drawbacks, including major logistic efforts
and risk of organ damage during perfusion and transport.
Our group, therefore, focused on the practicability of machine liver perfusion.
We developed an endischemic hypothermic oxygenated perfusion (HOPE) concept.
This technique can be easily applied in the operation room shortly before
transplantation of the recipient, thus after organ transport and back table
preparation.
Recently, the beneficial effect of such approach has been confirmed in human
liver grafts by a phase I non randomized trial. These results prove feasibility
and safety of an endischemic hypothermic machine perfusion approach and warrant
further randomized studies.

We therefore plan to test now HOPE in standard human grafts from brain death
donors by a multicenter prospective randomized trial.

The purpose of this study is, in a phase II randomized trial, to test a newly
developed machine perfusion technique of human liver allografts before
transplantation.

An international, multicenter, prospective, randomized, interventional, clincal
study with two parallel groups (intervention and control).

In the intervention group liver grafts will be subjected to two hours of
hypothermic, oxygenated perfusion(HOPE) at the end of SCS and before
implantation. In the control group donor liver grafts will be preserved in
accordance to standard practice by SCS only, without any further intervention.

Patients participating in this trial will experience minimal burden. There are
only two differences compared with the routine practice: half of the livers
will undergo HOPE and patients will undergo a MRCP at twelve months after
transplantation. The intervention, HOPE, is associated with a non-significant
risk of injury of the isolated liver due to perfusion pressure or perfusion
failure. The perfusion pressures in this protocol are very low and are reported
to cause no harm to the organ. In case of perfusion failure, the liver can
easily and quickly (within minutes) be brought to the same conditions as in the
control group. There is a burden but there are no risks related to MRCP, which
is planned during a routine hospital visit. When the intervention is effective
in reducing post operative morbidity and mortality, the patients participating
in this trial benefit substantially when they are randomized to the
intervention group. This study can only be permored in these patients because
they undergo liver tranpslantation.