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

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

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

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

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

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

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 2.8-3.5 <2.8 Prothrombin time, prolongation (s) <4.0 4.0-6.0 > 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%

MELD score predicted survival at 3 months MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43 Gastroenterology 2003 124, 91-96

Addition of Sodium to MELD Na-MELD / UKELD N Engl J Med 2008; 359:1018-1026

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

No disease specific criteria for transplantation prioritization

PSC risk score The Mayo Risk Score (R) = (0.0295 * (age in years)) + (0.5373 * LN(total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * LN(AST in IU/L) + (1.2426 * (points for variceal bleeding)) Age Varices (heads up that transplant is often needed 2-3 years) Liver inflammation

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

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.

Recurrent PSC Rowe et al. Transplant Int. 2008

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

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

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!