Liver Transplantation
Conditions
Brief summary
Hypothermic machine perfusion (HMP) has been shown to be beneficial to preserve extended criteria donor (ECD) livers for transplantation. Normothermic machine perfusion (NMP) had the same benefits and also the convenience on liver quality assessment. The investigators proposed to do sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers by using an institutional-developed perfusion device for liver transplantation.
Detailed description
Liver transplantation is a successful therapy on the patients with end-stage liver disease, however is limited by the shortage of donor organs. Donor criteria were expanded in the past decades, however the extended criteria donor (ECD) livers may induce a higher risk of complications. Static cold storage (SCS) is the standard procedure for ex vivo liver preservation for about 4 decades, but has the limitation on preserving ECD livers and especially the inconvenience to evaluate liver quality prior to transplantation. Hypothermic (4-8 Celsius degree) machine perfusion (HMP) and Normothermic (35-37 Celsius degree) machine perfusion (NMP) have been shown to be beneficial to preserve extended criteria donor (ECD) livers respectively. NMP also had the convenience on liver quality assessment. The investigators had an institutional-developed device for liver NMP used on 25 patients with the FDA's IDE approval. In the present study the investigators are proposing to expand the use of the device on sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers. This will be a single center prospective pilot study. The liver metabolism and hydrodynamics during perfusion will be recorded. The transplant procedure and post-transplant care will follow the clinical standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of patient survival and primary non function (PNF) within 30 days after transplantation, while the secondary end points will be: Early Allograft Dysfunction (EAD), 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, surgical outcomes (operative time, transfusion requirement etc.), rate of post-transplant kidney failure, assessment of histological ischemia reperfusion (liver and bile duct), rate of vascular complications, rate of biliary complications, hospital and ICU length of stay, rejection rate, infection rate, the ability to predict function based on on-pump viability markers, and the incidence of adverse effect (AE).
Interventions
DEVICELiver Machine Perfusion (MP) device
Donor livers will have ex vivo continuous perfusion on the institutional-developed Liver MP device. The temperature of liver grafts will be controlled during perfusion.
Sponsors
Koji Hashimoto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eighteen extended criteria donor livers will be transplanted after receiving sequential hypothermic and normothermic machine perfusion preservation prior to transplantation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing liver transplantation * Age 18 or older at the time of transplantation * Willingness and ability to comply with the study procedures * Signed Informed Consent Form
Exclusion criteria
* Recipient of partial grafts (split and living donors) * Mentally or legally incapacitated subjects * Inability to understand the procedures due to language barriers * Multiorgan transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| patient survival at 1 month post-transplant | 1 month post-transplant | Patient survival will be recorded at 1 month post transplantation. |
| graft survival at 1 month post-transplant | 1 month post-transplant | graft survival will be recorded at 1 month post transplantation. The allograft will be considered lost if a patient has a primary non function (PNF), liver re-transplant or in the event of patient death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| rate of post-transplant early allograft dysfunction (EAD) | in the first 7 days after transplantation | EAD is defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin ≥10mg/dL on post-operative day (POD) 7, international normalized ratio (INR) ≥1.6 on POD 7, and alanine or aspartate aminotransferases (ALT or AST) \>2000 IU/L within the first 7 days. |
| patient survival at 6 month post-transplant | 6 month post-transplant | patient survival will be recorded at 6 months post transplantation. |
| graft survival at 6 month post-transplant | 6 month post-transplant | graft survival will be recorded at 6 month post transplantation. The allograft will be considered lost if a patient has a primary non function (PNF), liver re-transplant or in the event of patient death. |
| Estimated blood loss at transplant surgery | during surgery | Estimated blood loss (ml) during transplant surgery |
| international normalized ratio on post-operative day 7 | on post-operative day 7 | international normalized ratio on post-operative day 7 |
| peak aspartate aminotransferases in the first 7 days after transplantation | in the first 7 days after transplantation | peak level (U/L) of aspartate aminotransferases in the first 7 days after transplantation |
| Hospital length of stay | up to 36 weeks | Length of stay (days) in the hospital at the time for transplantation |
| ICU length of stay | up to 36weeks | Length of stay (days) in ICU at the time after liver transplantation |
| peak alanine aminotransferases in the first 7 days after transplantation | in the first 7 days after transplantation | peak level (U/L) of alanine aminotransferases in the first 7 days after transplantation |
| total bilirubin on post-operative day 7 | on post-operative day 7 | total bilirubin (mg/dL) on post-operative day 7 |
Countries
United States
Outcome results
None listed