Liver transplantation is often performed to treat liver cancer, or hepatocellular carcinoma (HCC), in patients with impaired liver function due to cirrhosis. A shortcoming, however, is tumor recurrence after transplantation. Approximately 15 % of patients receiving livers develop recurrence and this depends on the quality of the liver received. Machine liver perfusion, for example, hypothermic oxygenated liver perfusion (HOPE), which means that the organ is perfused with an oxygen-rich fluid in a cold environment before transplantation, is a novel method to improve the quality of livers before implantation. The standard of care is cold storage without perfusion. The objective of this study is to compare the survival after tumor recurrence of patients after liver transplantation for HCC between perfused and not perfused livers. This study's hypothesis is that survival without tumor recurrence is improved when the liver is perfused before implantation. The study involves transplant centers worldwide, and adults with HCC waiting for liver transplantation are included. 220 Patients will be recruited within 12 months and then observed for at least 2 years after transplantation. To provide the most valid results, the patients will be randomly allocated to either the organ perfusion group or a control group with standard-of-care cold storage of the organ.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
220
All study centres will use either VitaSmart, Liver assist or Perlife devices for machine liver perfusion, with a pressure controlled hypothermic oxygenated liver perfusion through the portal vein (HOPE) or through the portal vein and the hepatic artery (DHOPE), targeting a flow rate between 200-250 ml/min at a pressure of 3 mmHg, and a perfusate temperature between 8-12°C. The perfusate consists of 3L re-circulating Belzer MPS® (Bridge to Life Ltd.) with an active oxygenation (70-110 kPa). The minimum perfusion duration is defined at 2 hours, while perfusion is generally continued until the recipient hepatectomy is completed. The perfusion will exclusively be performed in the recipient centre after initial cold storage and bench preparation of the liver for implantation. The perfusion devices are routinely used in all participating centres.
Conventional cold storage at 4°C will be performed with precooled preservation solution according to local standard of care. For cold storage at the Swiss centres, IGL-1 (Institute George Lopez) is used for cold storage. Liver transplant centres in other European countries, use mainly three other storage solutions (Histidine trypophan-ketoglutarat, HTK and University of Wisconsin, UW solution, Celsior) in accordance to their national guidelines.
Rutgers New Jersey Medical School (New York)
New York, New York, United States
NOT_YET_RECRUITINGCleveland Clinic
Cleveland, Ohio, United States
NOT_YET_RECRUITINGMedical University of Innsbruck
Innsbruck, Austria
RECRUITINGMedical University of Vienna
Vienna, Austria
Recurrence free survival
Post transplant HCC recurrence free survival, i.e. the time interval a patient is alive without HCC recurrence after transplantation, i.e., until either HCC recurrence is observed, or the patient dies from any cause.
Time frame: 24 months
HCC recurrence (while alive)
Number of HCC recurrences
Time frame: 24 months
HCC recurrence (while alive)
Time to recurrence of HCC
Time frame: 24 months
HCC-related death
Death related to HCC
Time frame: 24 months
HCC-related death
Time to HCC related death
Time frame: 24 months
Death from any other causes than HCC
Death not related to HCC
Time frame: 24 months
Death from any other causes than HCC
Time to death not related to HCC
Time frame: 24 months
Mean number of circulating tumour deoxyribonucleic acid (DNA) in blood
This will be measured before transplantation (baseline), at discharge and at 6 months after transplantation. This endpoint will add information on the risk of tumour recurrence by seeding circulating cells.
Time frame: 6 months
Mean number of high-mobility-group-protein B1 (HMGB-1) in blood
This will be measured at the time of transplantation (baseline) and 1 week after transplantation. This endpoint will add information on danger signalling in both study arms during early and late reperfusion.
Time frame: 1 week
Median Rejection Activity Index
The Rejection Activity Index (RAI) in liver histology (biopsy) is performed at 6 months after transplantation. This endpoint assessed in liver histology (biopsy) will show endothelial and T cell activation in implanted livers within the first months after 6 months. The RAI can be used to score liver allograft biopsies with acute rejection. The scale is from 1 to 9, higher scores mean more severe signs of rejection.
Time frame: 6 months
Liver related complications
This endpoint will allow to assess the association between initial graft injury and liver specific complications in both study arms.
Time frame: 24 months
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University Hospitals Leuven
Leuven, Belgium
RECRUITINGInstitut de Recherche Expérimentale et Clinique (IREC) UCLouvain (Brussels)
Woluwe-Saint-Lambert, Belgium
RECRUITINGInstitute for Clinical and Experimental Medicine (IKEM) (Prague)
Prague, Czechia
RECRUITINGCopenhagen University Hospital
Copenhagen, Denmark
RECRUITINGHôpital de la Croix-Rousse (Lyon)
Lyon, France
NOT_YET_RECRUITINGUniversitätsklinikum Essen
Essen, Germany
NOT_YET_RECRUITING...and 27 more locations