1. When is it Time for a Transplant? CAHN Conference February 25, 2011 Sandy Williams RN(EC), MScN, NP Nurse Practitioner / Transplant Coordinator London Health Sciences Centre 0

2. Objectives Review the indications for liver transplantation Understand – Optimal Timing – Information needed to facilitate the assessment – Transplant Process Consider Long-term outcomes & concerns

3. Who Needs a Liver Transplant? End-stage organ failure Tumour No other surgical or medical option Limited life span “Sick enough to warrant the risks & healthy enough to survive the surgery”

4. Patient’s Fears about Assessment 3

5. Purpose of the Transplant Assessment To allow patient to get to know the transplant team, have their questions answered, understand the process & expected outcome To establish rapport with the patient & family so that they have confidence in the team & see them as their advocates To assess the need for a transplant To reveal any contraindications or additional risk factors for surgery 4

6. Helpful Referral Information Comprehensive health history – current symptoms, past surgery, medications etc. Recent blood work, U/S, endoscopies, echocardiogram, CT scans, O.R. notes investigations related to diagnosis of liver disease Psycho-social situation, family supports, finances/insurance coverage 5

7. Transplant Assessment Protocol Consults – surgery, medicine, social work, dietician, recipient coordinator Labs – comprehensive chemistry, serology, tumour markers Echocardiogram/MIBI Doppler U/S +/-CT scan Endoscopy/Colonoscopy Other consults & investigations as indicated by medical history & test results 6

8. Possible Outcomes of Assessment Too well – transplant not necessary at this time or other treatment is sufficient Appropriate for listing Unsuitable – because they have sepsis or require heart surgery, ETOH rehab before transplant Too ill & will never be appropriate for transplantation 7

9. Transplant Patient Selection Criteria Accepted indications for Liver Transplantation – Fulminant Failure (acute illness) – Hepatic malignancy (HCC) within criteria – Decompensated chronic liver diseases – Alcohol-related disease (abstinence, insight & rehab) – HCV, HBV, Autoimmune Hepatitis – Extra-hepatic conditions (hepatopulmonary ) – Inherited metabolic liver disease (FAP, Wilson, etc.)

10. Contraindications to Transplant Inability to withstand or benefit from transplant Extrahepatic or extensive tumour Other life-threatening illness or Sepsis Less than 50% chance of surviving 5 years Unwilling to follow healthcare advice Too well to warrant the risks Lack of social support Patient does not wish to have a transplant 9

11. Adult Recipients : Etiology Primary Diagnosis Hepatitis C35% Autoimmune (AIH, PBC, PSC)21% NASH/cryptogenic17% Alcohol-related11% Fulminant failure5% Hepatitis B5% Metabolic disease3% HCC (tumour)15% Re-transplant8%

12. Symptoms of Liver Disease Hyperbilirubinemia Renal dysfunction Coagulopathy Ascites/Edema/Effusions Hypoalbuminemia Bleeding Fatigue  Decreased LOC->Coma Muscle wasting Hypoglycemia Itch 11

13. Optimizing Pre-Op Condition Maintain nutrition/conditioning -supplements, low salt diet & exercise (rarely necessary to restrict protein) Manage ascites/effusions – diuretics, diet, TIPS Monitor for renal failure, electrolyte imbalance & tumours Prevent Bleeding – beta blockers & banding Prevent encephalopathy – lactulose, antibiotics Treat itch – cholestyramine, rifampin, sertraline Prevent peritonitis – ciprofloxin Ensure realistic expectations of wait time, recovery & post-op quality of life 12

14. Viral Hepatitis – Pre-op Care Decrease viral load as much as possible as this impacts long-term survival Monitor for usual liver failure symptoms (particularly prone to tumours) Reinforce the fact that a liver transplant doesn’t clear the virus & that post-transplant viral treatment will be required 13

15. Surveillance for Pre-op Patients Blood work as indicated by condition – including alphafetoprotein & viral loads U/S every 6 months (may require CT scans) Echocardiogram yearly Routine investigations for age, gender & specific disease “another important part of pre-transplant care is providing understanding & compassion for their situation” 14

16. Life threatening Pre-op Complications Patients with liver disease often don’t die from liver failure, but from complications related to poor liver function Hepatorenal syndrome & electrolyte/glucose & fluid imbalance Sepsis (pneumonia, peritonitis) Malnutrition & Weakness that makes them prone to sepsis Bleeding can often be controlled – banding/TIPS Coma can usually be reversed with lactulose, fluids & antibiotics (depending on the cause) 15

17. Alcohol, Methadone & Narcotic Use Significant ETOH history requires at least 6 months abstinence +insight +relapse prevention program Stable methadone use is not a contraindication to transplantation in many programs Narcotic use may be necessary for chronic pain, however should be weaned if possible to prevent encephalopathy 16

18. Transplant for people living with HIV People who have liver disease & are HIV+ may be candidates for liver transplant if their HIV viral load is undetectable Stable CD4 counts They meet the standard criteria for transplant No significant HIV related illness (such as Kaposi’s sarcoma) “ the difficulty with HIV+ patients is that by the time their liver disease has progressed to the point of needing a transplant, the HIV has also progressed such that they may not be appropriate” *The interaction of the transplant anti-rejection medications & HAART drugs makes it difficult to manage these patients after the transplant 17

19. Hepatocellular Carcinoma - Milan Criteria The accepted listing criteria for transplant candidates with HCC Single lesion, ≤ 5 cm in size, or No more then 3 lesions, all ≤ 3cm No extrahepatic disease, vascular invasion or nodes Canadian Liver Transplant Study Group There are other tumour criteria & each program decides what is acceptable for their group

20. People who decline transfusions Patients who don’t accept blood transfusions may be eligible for liver transplant if; Low INR, adequate hemoglobin & platelets Vascular anatomy is straightforward Limited prior abdominal surgery Patient is made aware that if their blood work deteriorates they may be removed from the list 19

21. Quantifying Severity of Illness Not everyone with cirrhosis needs a transplant & we don’t rush into it because of the potential toxicity of the immunosuppression For those who do have life-threatening illness, it is necessary to rank the severity of illness in order to prevent pre-transplant deaths The aim is for everyone to have equitable access to the limited resource 20

22. Model End Stage Liver Disease: MELD score MELD (or NaMELD) – Based on objective indices Albumin, INR, Bilirubin and creatinine – Meant to bring fairness to patient selection & ensure that transplantation is needed – Doesn’t always reflect degree of illness for those with hepatopulmonary syndrome, urea cycle defects – Several variations of this formula – Criticized for favouring patients with tumours

23. MELD Calculator

24. Who Gets the Organ? Sickest patient Compatible blood type Size compatible Longest Waiting Time

25. Liver Transplantation in Canada: Current Status Patient survival: 1yr = 92%, 3yr = 80%, 10yr = 60% Approximately 420 Liver transplants in Canada/year – 7 adult centers – 800 patients on liver transplant waiting lists – 150 deaths/year on waiting list

26. Expanding the Donor Pool Living Donor Liver Transplantation – Adult to Child, Adult to Adult – (relative, friend, or anonymous) Split Liver Transplantation Donation After Cardiac Death (DCD) Web-based ‘Matching’ service (not in Canada) Domino (amyloid liver given to another patient)

27. Living Donor Liver Transplantation

28. Split Liver Transplantation Left Lateral Segment Left Hepatic Vein Right Portal Vein with Common Portal Vein Left Portal Vein Right Hepatic Artery with Celiac Axis Right Hepatic Duct Left Hepatic Duct Left Hepatic Artery

29. Advantages of Living Donation Decreased waiting time Reduced cold ischemic time Elective procedure Increased number of cadaver organs for others waiting for transplant

30. 29 Donation After Cardiac Death Occurs in hopeless cases in the hospital where the decision to withdraw life support is made (decision is independent of the decision to donate organs). These patients don’t meet the conventional “brain death” criteria Organ donation occurs immediately once the heart has stopped and the patient is declared dead This type of donation was initiated in response to families who were disappointed when their loved ones weren’t able to donate due to strict criteria

31. When a donor becomes available Patient is called in to hospital from home or local hospital Standard pre-op tests are performed The transplant team travels to wherever the donor is to inspect the organ & perform the hepatectomy The liver is flushed with a preservation solution & delivered to the transplant hospital 30

32. Transplant Surgery Takes 5-8 hours Starts with careful removal of patient’s liver (which is sent to pathology) Requires connecting veins, arteries & bile ducts Immunosuppression starts in the operating room Bile flow starts immediately & coagulation improves Patients then go directly to ICU 31

33. Expected Peri-Operative Course Brief ICU stay Up walking within a few days Able to walk a flight of stairs before discharge from hospital Incision heals within 2 weeks Leave hospital in 1-3 weeks & stay in town for another week 32

34. Follow-Up Care & Advice Lifelong Immunosuppression Regular blood tests & check-ups Encouraged to be active - live a normal & healthy lifestyle Transplant team available for transplant- related concerns & family doctor can manage routine medical care 33

35. Post-Op Issues In Liver Transplantation Long Term Issues – Immunosuppression – side effects – Comorbidities – diabetes, heart disease – Renal dysfunction – Obesity – Recurrent disease & return to alcohol misuse – Malignancies – lymphoma, skin cancer – Failed expectations

36. Post-transplant Disease Recurrence HCV 100% (5yr -30%cirrhosis) HBV100% without prophylaxis AIH/PBC/PSC20% NASH Up to 80% HCC Depends on criteria Patients may have some recurrence of their disease but usually not severe enough to require a second transplant

37. Re-transplant for Hepatitis C Very poor outcomes if the patient has liver failure within 5 years of the transplant Patients with severe recurrent Hep C are prone to diabetes & renal failure & this combination makes getting to a second transplant difficult & surviving a second transplant unlikely 36

38. Quality of Life after Transplant Return to work & school within 2-6 months Able to travel, play sports & have children Most recipients rate their quality of life as good or excellent 37

39. So…… What if I have questions??? If you have questions about referring a patient for transplant, please contact your local transplant coordinator or other transplant team members – we’re happy to take your call!! 38

40. May your liver be smooth & you mind always clear, May you know only laughter throughout the year