Hypothermic Machine Preservation-Phase 2

It is our hypothesis that liver machine perfusion will increase the safe utilization of the existing supply of extended criteria donor (ECD) livers by (1) increasing the quality and duration of preservation thereby reducing the clinical effects reperfusion injury (2) improving early outcomes in patients receiving ECD liver allografts (3) developing reliable markers for pretransplant assessment of the potential graft (4) giving surgeons more confidence when transplanting ECD livers and (5) allowing an avenue for ex vivo manipulation of the liver to protect or restore a transiently injured liver.

The proposed study is a matched cohort design. Potential subjects will be recruited from the Center for Liver Disease and Transplantation (CLDT) active Liver Transplant Waiting List. The Principal Investigator as well as the CoInvestigators, are all actively involved in the pre transplant evaluation process. Patients who are on the Waiting List and have provided written consent to receive an ECD graft will be recruited for this trial. Subjects will be matched with 24 historical control patients who received similar cold stored ECD grafts. Subjects will be matched on known covariates including donor age, donation after cardiac death, steatosis, both warm and cold ischemia times, recipient age, Model End-Stage Liver Disease (MELD) score and disease etiology.

Subjects will be noncritically ill, not in an intensive care unit, and have a MELD < 35 in order to minimize the variability in outcome in the sickest patients. All subjects must provide written informed consent and meet the inclusion and exclusion criteria.

Subjects will be followed for one year post transplantation, in conjunction with their routine liver transplant followup appointments. Retention of subjects for this trial will not be a challenge, in that the followup visit time points (postoperative days 1 through the discharge date, 7, 14, 30, 90, 180 and 365) are all consistent with our standard of care.

Inclusion criteria

• Signed written informed IRB consent by patient or patient's legally appointed representative.
• Be at least 18 years of age; male or female.
• Listed with UNOS for liver transplantation.
• Organ declined by at least one transplant center
• Extended criteria donor as defined by:

• Presence of hepatitis C antibody
• Donation after Cardiac Death (DCD)
• Severe Hypernatremia: donor serum sodium >165 meq/L for at least 12 hours prior to procurement
• Donor age ≥65 years
• Presence of significant steatosis >25% macrovesicular by biopsy
• Evidence of significant donor ischemic injury
• Current donor serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1000 IU/L
• Ischemic injury evidenced by prolonged hypotension, high pressor requirement and/or rising serum liver function tests or one test more than five times the upper limit of normal (AST, ALT, or Total Bilirubin)

Exclusion criteria

• Patients in whom the donor liver will be subjected to less than 4 hours of cold ischemia (surgeon desires immediate implantation)
• Patient hospitalized in intensive care unit (ICU) at time of transplantation and/or physiologic MELD score >35
• Dual organ recipient
• ABO incompatibility
• Retransplantation