Background: A frequent and increasing indication for liver transplantation (LT) is hepatocellular carcinoma (HCC). However, despite strict selection criteria, HCC recurrence after LT occurs in a relevant proportion of patients and is associated with an unfavorable prognosis. Hypothermic oxygenated perfusion (HOPE) is a novel machine liver perfusion approach to optimize liver grafts before implantation and has been suggested to decrease graft inflammation with potential anti-cancer effects. Methods: HOPE4Cancer is an international, multicentric, parallel group, randomized controlled trial comparing HOPE performed after initial cold storage (intervention) with conventional cold storage alone (control) in a 1:1 allocation ratio. Adult recipients with proven HCC will be included for transplantation of a DBD (donation after brain death) Liver graft. The minimum perfusion duration is defined at 2 h and perfusion is generally continued until the recipient hepatectomy is completed. The conventional cold storage at 4 °C will be performed with a precooled preservation solution according to the local standard of care. The primary endpoint is defined as post-transplant HCC recurrence-free survival, i.e., the time interval a patient is alive without HCC recurrence after transplantation. Secondary endpoints are the single components of the events considered for the primary outcome (i.e., HCC recurrence, HCC-related death, death from any other causes than HCC), circulating tumor DNA, high-mobility-group-protein B1 in the blood, the Rejection Activity index, and the number of liver-related complications experienced by the patient. Discussion: HOPE4Cancer investigates if cold storage plus end-ischemically applied HOPE in DBD LT is superior to conventional cold storage of liver grafts in terms of post-transplant HCC recurrence-free survival. The results will indicate for the first time whether ex situ HOPE before transplant has an anti-cancer potential compared to transplantation of un-perfused livers. Trial registration: ClinicalTrials.gov NCT06717919. Registered on December 5, 2024.
Hypothermic oxygenated perfusion (HOPE) against cancer recurrence after liver transplantation for hepatocellular carcinoma—study protocol for an international multicenter randomized controlled trial (HOPE4Cancer) / J. Eden, P.C. Müller, C. Kuemmerli, F. Peters, T. Litke, A. Kranich, A.E. Kremer, S. Von Felten, P. Dutkowski, N. Null, V.E. De Meijer, L. Fischer, U. Cillo, R. De Carlis, V. Mazzaferro, R.J. Porte, J. Pirenne, A. Schlegel, J.V. Guarrera, G. Berlakovich, J. Fronek, G. Lurje, J. Mittler, M. Drefs, P. Compagnon, M. Cortes-Cerisuelo, J.M. Pollok, B. Fiore, R. Sanabria-Mateos, C. Tschuor, C. Van Beekum, U.P. Neumann, G.C. Oniscu, P. Ignatavicius, X. Muller, D. Monbaliu, S. Schneeberger, P. Domagala, P. Line, U. Baccarani, E. Bonaccorsi, R. Figueiredo, P. Kron. - In: TRIALS. - ISSN 1745-6215. - 26:1(2025 Sep 26), pp. 369.1-369.15. [10.1186/s13063-025-09120-1]
Hypothermic oxygenated perfusion (HOPE) against cancer recurrence after liver transplantation for hepatocellular carcinoma—study protocol for an international multicenter randomized controlled trial (HOPE4Cancer)
V. Mazzaferro;
2025
Abstract
Background: A frequent and increasing indication for liver transplantation (LT) is hepatocellular carcinoma (HCC). However, despite strict selection criteria, HCC recurrence after LT occurs in a relevant proportion of patients and is associated with an unfavorable prognosis. Hypothermic oxygenated perfusion (HOPE) is a novel machine liver perfusion approach to optimize liver grafts before implantation and has been suggested to decrease graft inflammation with potential anti-cancer effects. Methods: HOPE4Cancer is an international, multicentric, parallel group, randomized controlled trial comparing HOPE performed after initial cold storage (intervention) with conventional cold storage alone (control) in a 1:1 allocation ratio. Adult recipients with proven HCC will be included for transplantation of a DBD (donation after brain death) Liver graft. The minimum perfusion duration is defined at 2 h and perfusion is generally continued until the recipient hepatectomy is completed. The conventional cold storage at 4 °C will be performed with a precooled preservation solution according to the local standard of care. The primary endpoint is defined as post-transplant HCC recurrence-free survival, i.e., the time interval a patient is alive without HCC recurrence after transplantation. Secondary endpoints are the single components of the events considered for the primary outcome (i.e., HCC recurrence, HCC-related death, death from any other causes than HCC), circulating tumor DNA, high-mobility-group-protein B1 in the blood, the Rejection Activity index, and the number of liver-related complications experienced by the patient. Discussion: HOPE4Cancer investigates if cold storage plus end-ischemically applied HOPE in DBD LT is superior to conventional cold storage of liver grafts in terms of post-transplant HCC recurrence-free survival. The results will indicate for the first time whether ex situ HOPE before transplant has an anti-cancer potential compared to transplantation of un-perfused livers. Trial registration: ClinicalTrials.gov NCT06717919. Registered on December 5, 2024.
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