Livers can currently be preserved outside the body for up to 24 hours using ice-cold temperatures and a special chemical solution developed by NIH-funded scientists at the University of Wisconsin-Madison in 1983. Organ preservation solutions are used to maintain the hypothermic organ in optimal condition from the time of explantation until implantation by using principles like hypothermia to reduce cellular metabolism and maintaining cell membrane integrity. Following liver transplantation, patients are placed on lifelong immunosuppressive drugs to prevent rejection, with drug levels carefully monitored and adjusted for each patient.

1. Preserving Liver Transplantation
By : MONA YADAV
Group : 3
Course : 6th

2. Preserving Liver for
Transplantation
Extending the time organs can survive outside the body would allow
organs to be transported across greater distances. It would also improve
safety by increasing time for preparation and planning. The long-term
preservation of human organs, however, is challenging. Organs have
multiple cell types and structures that react differently to temperatures
below freezing. Livers can currently be preserved outside the body for up
to 24 hours using ice-cold temperatures and a special chemical solution
developed by NIH-funded scientists at the University of Wisconsin-
Madison in 1983.

3. History of Organ Preservation
• Simple cooling with cold solution
• Continuous hypothermic perfusion
• Collins (1967)
• Euro-Collins (1980)
• University of Wisconsin - ViaSpan
(1986)(UW)
• HTK - Custodiol (1980’s)

4. Organ Preservation Solutions
Preservation solutions are used to
maintain the hypothermic organ in
optimal condition from the time of
explantation until implantation

5. Principles of Organ Preservation
• Exsanguination to reduce
intravascular thrombosis
• Hypothermia to reduce
cellular metabolism
• Maintain cell membrane
integrity to avoid cellular
swelling
• Susceptibility to cold
ischemic injury: vascular
endothelium > parenchymal
cells

6. Ischemia
• Decreased mitochondrial
function
– Anaerobic conditions -
depletion of ATP
– Alterations in ion
permeability
– Accumulation of lactate
• Accumulation of hypoxanthine
• Cell swelling
• Cytosolic calcium
accumulation

7. Reperfusion
• Generation of reactive oxygen
species
• Increased oxidative stress
• Lipid peroxidation of cellular
membranes
• Free radical formation leads to
cellular destruction
• Results in macrophage/Kupffer
cell activation
– Increased serum tumor
necrosis factor (TNF)
• Damage can lead to prolonged
hypoxia after reperfusion

8. • High potassium, glucose, and phosphate-based
solution
• Designed to mimic composition of intracellular fluid
• Low cost
• Poor preservation quality
• Short preservation times achievable
Euro-Collins Solution

9. • Use of impermeant molecules, lactobionate and
raffinose, in preventing cell swelling
• First developed for and applied in preservation of
canine pancreas
• Hydroxyethyl starch to minimize interstitial edema
during machine perfusion, not necessary during cold
storage
• High [K+], low [Na+]
UW Solution

10. • Developed as cardioplegia
• Low potassium
• High buffering capacity of histidine
• No colloid - viscosity equal to that of pure water
from 1 to 350C, with mean flow rate 3X that of
UW solution at equal perfusion pressure -
organs exsanguinate and cool down to lower
temperatures more rapidly than with UW
HTK Solution (Custodiol)

11. Indications
 Fulminant hepatic failure
 Complications of cirrhosis
Ascites
Encephalopathy
Synthetic dysfunction
Liver cancer
Chronic gastrointestinal
blood loss due to portal
hypertensive
 Systemic complications of
chronic liver disease
Hepatopulmonary
syndrome
Portopulmonary
hypertension
 Liver-based metabolic
conditions causing systemic
disease
1-antitrypsin deficiency
Wilson’s disease
Urea cycle enzyme
deficiencies
Glycogen storage
disease
Tyrosemia

12. Contraindications to Liver Transplantation
Absolute
 Active extrahepatic malignancy
 Hepatic malignancy with macrovascular or diffuse tumor
invasion
 Active and uncontrolled infection outside of the
hepatobiliary system
 Active substance or alcohol abuse
 Severe cardiopulmonary or other comorbid conditions
 Psychosocial factors that would likely preclude recovery
after
transplantation
 Technical and/or anatomical barriers
 Brain death

13. Follow-up
Following transplantation, all patients are placed
on immunosuppressive drugs to prevent rejection
of the new liver. These medications are usually
started in the operating room and are continued
thereafter. The dose of the immunosuppression
agent needed varies from patient to patient
depending on the likelihood of rejection.

14. Immunosuppression must be balanced carefully against
the patient's own immune system. Adjusting the dose
specifically for each patient helps avoid the risk of
postoperative infections, tumor development, and liver
rejection. The dose of immunosuppression agents varies
between patients and may vary with time in a particular
patient. This explains the requirement of frequent blood
drawing, especially early after transplantation, because
absorption, metabolism, and dose requirements of these
drugs can vary significantly from day to day in the early
posttransplant period. As time passes, the amount of
immunosuppression needed to prevent organ rejection
usually decreases. Immunosuppression therapy is not
without risk and must be monitored closely.

15. Immunosuppression management is based on the following
principles:
•The doses used, adjusted over time, should be the minimum
necessary to prevent rejection.
•The risk of rejection is highest (40%) during the first 3-6
months after transplantation and decreases significantly
thereafter.
•Prolonged use of these medications can have severe and
significant adverse effects and toxicities.
•Some disease processes (ie, autoimmune diseases) are
more likely to produce rejection; drug levels in these patients
should be adjusted accordingly.
•Most medications are metabolized by the liver itself;
therefore, graft dysfunction can significantly alter drug levels.
•Other medications added to an immunosuppressive regimen
can lead to significant toxicities or to a lack of therapeutic
effect and subsequent rejection.