Please select the eligibility criteria that correspond to the clinical trial below.
Title: Hypothermic Oxygenated Machine Perfusion (HOPE) for Liver Transplantation of Human Liver Allografts From Extended Criteria Donors (ECD) in Donation After Brain Death (DBD); a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)
Brief Summary: The purpose of this study is to test the effects of hypothermic oxygenated machine perfusion (HOPE) in a phase-II prospective multicenter randomized clinical trial (RCT) on extended criteria donor allografts (ECD) in donation after brain death (DBD) orthotropic liver-transplantation (OLT) (HOPE-ECD-DBD). Human whole organ liver grafts will be submitted to 1-2 hours of HOPE via the portal vein directly before implantation and going to be compared to a control-group of patients transplanted after conventional cold storage (CCS). Primary (early graft injury) and secondary (e.g. postoperative complications, hospital stay, survival) objectives are going to be analysed in a 12 month follow up. Ischemia-reperfusion (I/R) injury and inflammation will be assessed using liver tissue, serum and bile samples as well as machine perfusion perfusate.

To improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with higher incidences of primary graft non-function (PNF) and/or delayed graft function (DGF). As such, several strategies have been developed aiming at "reconditioning" poor quality ECD grafts. HOPE has been tested intensively in pre-clinical animal experiments. Although, its known that HOPE can exert its reconditioning effect via cellular and mitochondrial pathways in the endothelial and parenchymal cells, there is still scarce evidence available on the exact subcellular mechanism of HOPE induced organ protection in the clinical scenario of liver transplantation. In donation after cardiac death (DCD) OLT, the positive effects of HOPE have been shown to reduce the incidence of biliary complications, mitochondrial damage and improve the overall cellular energy-status.

In the HOPE setting, organ perfusion is performed in the transplant center shortly before the actual implantation with oxygenated perfusate using an extra corporal organ perfusion system. The first clinical study with this promising technique was recently reported in a Swiss cohort of patients who received DCD allografts. In organ donation after brain death (DBD), the only legally accepted approach for organ donation in most countries, HOPE and its effect on early graft injury and postoperative complications remains to be elucidated.


Options:
A: Inclusion Criteria:

* For kidneys: donor age ≥ 60 years or 50-59 years with two or more of the sequent risk factors: death due to cerebrovascular accident, history of hypertension, donor serum creatinine \> 1.5 mg/dL, cold ischemia time (CIT) \> 20 h;
* For livers: donors with hemodynamic deterioration, donor age \> 65 years, donor body mass index \> 30 kg/m2, serum bilirubin \> 3 mg/dl, AST or ALT above three times the upper reference threshold, sodium \> 165 mmol/l, intensive care unit (ICU) stay \> 7 days, steatosis \> 40%, CIT \> 12 h.

Exclusion Criteria:

* Donor age ≤18 years;
* Donors after circulatory death (DCD) will be excluded, because Italian law requires 20 minutes of "no touch period" before death declaration, causing prolonged warm ischemia and subsequent mandatory perfusion of the organ.
* Split-liver recipients, liver transplantation (LT) for acute liver failure, pre-emptive renal transplant, dual kidney transplantation, and patients with intra-operative surgical complications before the organ implantation.
B: 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
C: Inclusion Criteria:

-Patients with signed informed consent, suffering from end stage-liver disease and/or malignant liver tumors listed for liver transplantation and receiving ECD organs.

ECD Criteria are defined as:

* Donors 65 years of age and older
* Intensive therapy of the donor was required before donation for at least 7 days, --Obesity of the donor with a Body Mass Index \> 30
* Fatty liver (with histology) \> 40 %
* Serum-Sodium \> 165 mmol/l
* Serum AST or ALT \> 3 x normal, Serum-Bilirubin \> 2 mg/dl)

Exclusion Criteria:

* Recipients of split of living donor liver transplants
* Previous liver transplantation
* Combined transplantations (liver-kidney, liver-lung, etc.)
* Participation in other liver related trials
* The subject received an investigational drug within 30 days prior to inclusion
* The subject is unwilling or unable to follow the procedures outlined in the protocol
* The subject is mentally or legally incapacitated
* Patient is not able to understand the procedures due to language barriers
* Family members of the investigators or employees of the participating department
D: Inclusion Criteria:

* Adult (≥18 years) patients with acute liver failure or liver cirrhosis (CHILD A, B or C) and/ or malignant liver tumors requiring liver transplantation
* Whole liver graft
* Signed informed consent

Exclusion Criteria:

* Split graft
* Living donor liver transplantation
* Grafts donated after cardiac arrest (DCD grafts)
* Domino transplantation
* Combined liver transplant
* Cold storage \> 15h
* acute and unexpected medical contraindication

Answer: C