Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe

University Medical Center Groningen10,000 enrolled

Overview

Machine perfusion (MP) has become routine clinical practice in liver transplantation. However, as the field has matured, direct randomized comparisons between distinct MP modalities have become increasingly impractical, given that donor and graft characteristics often predetermine the optimal preservation strategy. Consequently, many studies continue to reference historical benchmark cohorts from the pre-perfusion era, or use risk scores developed before routine utilization of MP. These cohorts, while once valuable, fail to account for the paradigm shift that MP has introduced. Likewise, commonly used donor- and recipient-based risk scores were developed prior to the adoption of MP. While these scores aim to assess survival or morbidity after transplantation, none of them guide decisions about MP use or the most suitable perfusion protocol. As MP technologies continue to evolve there is a critical need for an updated reference framework that accurately reflects current clinical practice and captures the best achievable outcomes across all MP modalities.

The aim of this study is to establish a reference framework for liver transplantation outcomes in the era of routine clinical machine perfusion. In addition, based on the collected real-world observational data, a target trial emulation approach will be applied.

Study Type

OBSERVATIONAL

Enrollment

10,000

Conditions

End-stage Liver Disease (ESLD)Acute Liver Failure Liver Cirrhosis Liver Transplantation

Interventions

Endischemic hypothermic oxygenated machine perfusion (any device)DEVICE

Endischemic single- or dual hypothermic oxygenated machine perfusion. Normothermic regional perfusion prior to single- or dual hypothermic oxygenated machine perfusion is eligible for inclusion.

Endischemic (back-to-base) normothermic machine perfusion (any device)DEVICE

Endischemic (back-to-base) normothermic machine perfusion. Normothermic regional perfusion prior to endischemic (back-to-base) normothermic machine perfusion is eligible for inclusion.

Continuous (device-to-donor) normothermic machine perfusion (any device)DEVICE

Continuous (device-to-donor) normothermic machine perfusion. Normothermic regional perfusion prior to continuous (device-to-donor) normothermic machine perfusion is eligible for inclusion.

Endischemic HOPE-COR-NMP (any device)DEVICE

Endischemic single or dual hypothermic oxygenated machine perfusion followed by controlled oxygenated rewarming and normothermic machine perfusion. Normothermic regional perfusion prior to HOPE-COR-NMP is eligible for inclusion.

Endischemic HOPE-NMP (any device)DEVICE

Endischemic single or dual hypothermic oxygenated machine perfusion followed by normothermic machine perfusion. Normothermic regional perfusion prior to HOPE-NMP is eligible for inclusion.

Normothermic regional perfusion (any device)DEVICE

Normothermic regional perfusion followed by static cold storage or any ex situ machine perfusion protocol.

Static cold storageOTHER

Preservation with static cold storage only, not preceeded by NRP, nor followed by ex situ machine perfusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * All postmortal livers accepted (transplanted and not-transplanted after machine perfusion) upon organ offer for patients \>18 years at the time of liver transplantation. * All donor types (DBD, DCD) * Preservation either with static cold storage alone or combined with machine perfusion (MP). * Donor livers underwent MP as part of routine clinical practice and the choice of perfusion protocol was made according to institutional standard practice. * Eligible MP protocols are: 1. end-ischemic single- or dual hypothermic oxygenated MP \[e(D)HOPE\], 2. end-ischemic (back-to-base) normothermic MP \[eNMP\], 3. continuous (device-to-donor) normothermic MP \[cNMP\], 4. e(D)HOPE followed by controlled oxygenated rewarming and normothermic MP \[e(D)HOPE-COR-NMP)\], 5. e(D)HOPE followed by normothermic MP \[e(D)HOPE-NMP\], or 6. Normothermic regional perfusion followed by SCS or an ex situ MP protocol. * A minimum follow-up of 12 months after liver transplantation is required. Exclusion Criteria: * Livers that were allocated to a MP protocol as part of a prospective randomized or interventional clinical trial comparing different preservation techniques or any other invention. * Living donor liver transplantation

Outcomes

Primary Outcomes

Death-censored graft survival

Defined as the time from liver transplantation until re-transplantation or death due to graft failure (analyzed using time-to-event methods).

Time frame: Actuarial survival 1-5 year post-transplantation

Overall patient survival

Defined as time from liver transplantation until re-transplantation or all-cause death (analyzed using time-to-event methods).

Time frame: Actuarial survival 1-5 year post-transplantation

Secondary Outcomes

Overall graft survival

Defined as time from liver transplantation until re-transplantation or all-cause death (analyzed using time-to-event methods)

Time frame: Actuarial survival 1-5 year post-transplantation

Incidence of major liver-related complications

Incidence of at least one biliary or vascular complication graded as Clavien-Dindo IIIb or higher, following the grading recommendations published: de Goeij FHC, Wehrle CJ, Abbassi F, et al. Mastering the narrative: Precision reporting of risk and outcomes in liver transplantation. J Hepatol. 2025;82(4):729-743. doi:10.1016/j.jhep.2024.11.013. Additionally, scoring accoring the Comprehensive Complication Index.

Time frame: within the transplant-related admission, and 1 year post-transplantation

Incidence of graft loss due to complications

Graft loss as a result of complications assessed separately for biliary complications, vascular complications, and rejection.