Acute Liver Failure, End-stage Liver Disease (ESLD), Liver Cirrhosis, Liver Transplantation
Conditions
Keywords
machine perfusion, liver transplantation, hypothermic machine perfusion, normothermic machine perfusion, normothermic regional perfusion, organ preservation, machine preservation
Brief summary
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.
Detailed description
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.
Interventions
DEVICEEndischemic hypothermic oxygenated machine perfusion (any 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.
DEVICEEndischemic (back-to-base) normothermic machine perfusion (any device)
Endischemic (back-to-base) normothermic machine perfusion. Normothermic regional perfusion prior to endischemic (back-to-base) normothermic machine perfusion is eligible for inclusion.
DEVICEContinuous (device-to-donor) normothermic machine perfusion (any device)
Continuous (device-to-donor) normothermic machine perfusion. Normothermic regional perfusion prior to continuous (device-to-donor) normothermic machine perfusion is eligible for inclusion.
DEVICEEndischemic HOPE-COR-NMP (any 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.
DEVICEEndischemic HOPE-NMP (any 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.
DEVICENormothermic regional perfusion (any device)
Normothermic regional perfusion followed by static cold storage or any ex situ machine perfusion protocol.
OTHERStatic cold storage
Preservation with static cold storage only, not preceeded by NRP, nor followed by ex situ machine perfusion.
Sponsors
University Medical Center Groningen
A.O.U. Città della Salute e della Scienza
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death-censored graft survival | Actuarial survival 1-5 year post-transplantation | Defined as the time from liver transplantation until re-transplantation or death due to graft failure (analyzed using time-to-event methods). |
| Overall patient survival | Actuarial survival 1-5 year post-transplantation | Defined as time from liver transplantation until re-transplantation or all-cause death (analyzed using time-to-event methods). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall graft survival | Actuarial survival 1-5 year post-transplantation | Defined as time from liver transplantation until re-transplantation or all-cause death (analyzed using time-to-event methods) |
| Incidence of major liver-related complications | within the transplant-related admission, and 1 year post-transplantation | 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. |
| Incidence of graft loss due to complications | within 1 year post-transplantation, up to 5 years post-transplantation | Graft loss as a result of complications assessed separately for biliary complications, vascular complications, and rejection. |
| Total number of clinically significant biliary complications | within 1 year post-transplantation, up to 5 years post-transplantation | Total number of any biliary complications requiring interventions (Clavien-Dindo grade IIIa or higher). |
| Incidence of biliary complications | within 1 year post-transplantation, up to 5 years post-transplantation | Biliary complications include: * Post-transplant cholangiopathy * Anastomotic strictures * Biliary leakage |
| Incidence of vascular complications | within 1 year post-transplantation, up to 5 years post-transplantation | Vascular complications include: * Hepatic artery thrombosis * Portal vein thrombosis * Venous outflow tract obstruction |
| Incidence of re-transplantation | within 1 year post-transplantation, up to 5 years post-transplantation | Re-transplantation for any cause. |
| Incidence of acute rejection | within 1 year post-transplantation, up to 5 years post-transplantation | — |
| Incidence of chronic rejection | within 1 year post-transplantation, up to 5 years post-transplantation | — |
| Incidence of recurrence of primary disease | within 1 year post-transplantation, up to 5 years post-transplantation | Histologically or radiologically confirmed recurrence, including recurrence of malignancies |
| Incidence of kidney injury | within 1 year post-transplantation, up to 5 years post-transplantation | Kidney injury includes: * Acute kidney injury * New-onset chronic kidney disease |
| Incidence of primary non-function | up to 1 week post-transplantation | Liver graft failure within the first 7 days of transplantation with patent liver vessels leading to re-transplantation or patient death |
| Patient-centered outcomes (measure of recovery and healthcare utilization) | within 1 year post-transplantation | Length of intensive care unit stay and length of initial hospital stay (starting at day of transplantation until day of discharge, measured in days) |
Countries
Austria, Belgium, Germany, Italy, Netherlands, Sweden, Switzerland, United Kingdom
Contacts
CONTACTSabrina Stimmeder, MD
PRINCIPAL_INVESTIGATORVincent E de Meijer, MD, PhD
University Medical Center Groningen
Outcome results
None listed