1. Liver transplantation and PSC
Bertus Eksteen
Aspen Woods Clinic and University of Calgary
Canada

2. Important considerations
MELD/ Na-MELD/ UKELD
Variant syndromes
Is a transplant required?
Current physical health
Expected outcomes at 5 years
Can the individual survive the procedure and subsequent 5 years?
Addictions
Social support frameworks
Eligibility concerns

3. Predicting timing to list for transplant
Risk of death without transplant
Year 1 liver transplant mortality 10-12%
Not counting morbidity
No prophylactic Tx for Cholangio Ca as risk is 2.5-3% per year

4. Equitable access Preferential Organ allocation for pediatric cases
Limited resource (not a human right)
Assigning minimum benefit requirements
Everyone benefits but what is enough ?
Reality of transplant waitlist
For every 2 individuals transplanted, 3 other individuals Succumb

5. Types of Transplants Donation after Brain death (DBD)
Limited supply
Full Liver
Short warm ischemia time
Donation after cardiac death (DCD)
Increasing use (labour intensive)
Longer recovery
Compromised sometimes by long warm ischemia times
Living-related Liver Donation (LRLD)
Increasing use
Half a liver
Risks to donor
Timed transplants but must be eligible for DBD or DCD

6. Current Selection tools
Best use in hepatocyte targeted diseases such as alcoholic liver disease, hepatitis B and Hepatitis C
Child Pugh Score
MELD Score
Na-MELD or UKELD score

7. Child Pugh Score Measure 1 point 2 points 3 points
Total bilirubin, μmol/L (mg/dL)
<34 (<2)
34-50 (2-3)
>50 (>3)
Serum albumin, g/dL
>3.5
<2.8
Prothrombin time, prolongation (s)
<4.0
> 6.0
Ascites
None
Mild
Moderate to Severe
Hepatic encephalopathy
Grade I-II (or suppressed with medication)
Grade III-IV (or refractory)
Points
Class
One year survival
Two year survival
5-6 A
100%
85%
7-9 B
81%
57%
10-15 C
45%
35%

8. MELD score predicted survival at 3 months
MELD = 3.78×ln[serum bilirubin (mg/dL)] ×ln[INR] ×ln[serum creatinine (mg/dL)]
Gastroenterology  , 91-96

9. Addition of Sodium to MELD Na-MELD / UKELD
N Engl J Med 2008; 359:

10. Variant Syndromes
Refractory or resistant Ascites
Hepatic encephalopathy
Malignancy (HCC/Cca)
Refractory Itching
Refractory Cholangitis
Metabolic diseases
Arbitrary score assignment and increases either scheduled or per patient condition

11. No disease specific criteria for transplantation prioritization

12. PSC risk score
The Mayo Risk Score (R) = ( * (age in years)) + ( * LN(total bilirubin in mg/dL)) - ( * (serum albumin in g/dL)) + ( * LN(AST in IU/L) + ( * (points for variceal bleeding))
Age
Varices (heads up that transplant is often needed 2-3 years)
Liver inflammation

13. iPSCSG transplant survey
14 Questions
Survey Monkey
33 responses
12 countries
Aim to understand practices across the network to transplantation and PSC

20. Summary of survey
Great inter-regional variability in transplant practices.
Lack of consistency to respond or be allowed to respond to features of PSC that are not captured by traditional models such as MELD.
Real need to understand and agree the impact of “variant syndromes” on PSC mortality or outcomes.
Equitable scoring system for PSC that is compatible with na-MELD for other diseases.

21. Recurrent PSC
Rowe et al. Transplant Int. 2008

22. Role of Colectomy in recurrent PSC
Neuberger Liver Transplantation 2009
Active IBD at transplant most significant predicator of recurrent disease

23. Recurrent PSC
Transplant doesn’t cure PSC and it does not prevent cholangio CA.
Donor factors (Ischemia times).
Type of transplant (LRLD from siblings with shared genetics).
Age of transplant.
Recurrent PSC versus chronic Rejection.
Activity of IBD
Need to define the optimum endpoint.
Symptom based score versus mucosal healing
Quality mucosal assessment by ileo-colonoscopy
Surgical versus Chemical colectomy

24. Summary Save many lives. Sign up to be an organ donor!
Importance of correct timing of transplant
It is not a cure
Attention to PSC specific features
Need for a useable PSC model that works with MELD
Save many lives. Sign up to be an organ donor!