Liver Transplantation for Alcoholic Liver Disease

1. Liver Transplantation for Alcoholic Liver Disease Liver Transplantation David Orr Hepatologist NZLTU

2. Milestones in Transplantation • 1948 ACTH and Corticosteroids • 1953 6-mercaptopurine • 1957 Kidney Transplantation (Murray) • 1963 Liver Transplantation (Starzl) • 1967 Successful Liver Transplanatation (Starzl) • 1979 Cyclosporine (Calne) • 1982 50% 1 year survival (Calne) • 1988 Living Related Liver transplant (Raia) • 1994 Living donor R lobe (Yamaoka) • 1997 Monosegmental Liver transplants (Rela)

3. Indications For LT • Acute hepatic failure • Early graft failure (PGNF, HAT) • Late graft failure (CR, biliary cirrhosis, HAT, recurrent disease) • Chronic Liver disease CPS>9 Severe bone disease (esp PBC/PSC) Uncontrolled variceal bleeding Hepatopulmonary syndrome Diuretic resistant ascites Portopulmonary hypertension Chronic hepatic encephalopathy Hepatorenal syndrome SBP HCC Severe malnutrition Intractable pruritis • Metabolic liver disease

4. Acute Liver Failure • Paracetamol Listing Criteria (Poor prognosis criteria: survival <5%) pH < 7.3 (after fluid resus) Or Grade III – IV HE INR > 8 Serum Cr > 300

5. Acute Liver Failure • Non Paracetamol INR > 8 (irrespective of HE grade) Or 3 of 5 Criteria 1. INR > 4 2. Age < 10 or >40 3. Aetiology: Drug induced or Non-A, Non-B 4. Bilirubin > 300 5. Jaundice to encephalopathy > 7 days

6. Acute Liver Failure • Aetiology Viral: Hep A, B, E (Rare: HSV, EBV, CMV) Drug: Paracetamol, Isoniazid/rifampicin, NSAIDs, Valproate, carbamazepine, Ecstasy, anaesthetic, phenytoin, MAOIs

7. Acute Liver Failure • Aetiology -AFLP, HELLP -Wilson’s: Coombes neg hemolytic anaemia, KF rings -Amanita phalloides: severe diarrhoea 5 hr post ingestion, ALF 4-5/7 -AIH -BCS -Lymphoma -Ischaemic hepatitis

8. Contraindications to LT

9. CADAVERIC ORGAN DONOR SHORTAGE Waiting List Registrants Donors UNOS July 2001

10. Median Waiting Times: Liver Transplant by Blood Type

11. Current Allocation Schema • Severity of Illness (Status) • Allocation determined by: • Blood Type • Waiting time • Size

12. Live Donor Liver Transplant

13. Living related liver transplant : Donor requirements • Unsolicited volunteer • Family member (not necessarily blood relative) • No clear medical contra-indications • Size appropriate • ABO matched • Age <50 • Normal liver, HIV negative

14. Donor problems • Biliary complications 6% • Re-operation 5% • Death <0.3% • Mean ICU Stay 0.5 days • Hospital Stay 6.4 days Brown et al. AASLD 2001

15. Recipient Issues • Retransplant rate 2.5% • Acute liver Failure 2% • Biliary complications 23% • Arterial complications 8% Brown et al. AASLD 2001

16. Common Problems after LT Diabetes NODM 15% Osteoporosis Increased risk in cholestatic liver diseases, long term steroids Obesity Hypertension CNI Hyperlipidemia Sirolimus Neurological Headache- CNI Hematological Anaemia. HCV related Viruses CMV, EBV, Herpes viruses Malignancy Skin, all solid tumours, PTLD Renal Failure CNI

17. What to watch for within the first week • Hepatic Artery thrombosis • Portal Vein thrombosis • Infections Bacterial/Viral/Fungal • Drug toxicity • Renal Impairment • Acute cellular rejection

18. Acute cellular Rejection • 40-50% of recipients within 1st year post transplant • Mainly in first month • High AST/ALT/Alk phos • Peripheral eosinophilia • Diagnose on liver biopsy

19. Histology ACR

20. Infection post Transplant • Month 1 Nosocomial infection Bacteria and fungi 19-28% of patients have bacteremia Staph, Enterococcus (50-60%) • Month 2-6 CMV

21. CMV • Herpesvirus • Highest risk are recipients from CMV mismatch or Recipients of OKT-3/Thymoglobulin • Without prophyllaxis (oral Valganciclovir), risk of symptomatic disease 64% • Fever, leukopenia, hepatitis in up to 25% Pneumonitis, GI infection • Predisposes: chronic rejection, worse HCV recurrence and fungal superinfection • Treat with iv Ganciclovir/oral Valganciclovir for 3 months

22. Early (< 30 days) Anastomotic bile leak Anastomotic stricture Bile leak at T tube exit Obstruction of T tube Sphincter of Oddi dysfunction Late (> 30 days) Anastomotic stricture Nonanastomotic strictures Bile leak on T tube removal Sphincter of Oddi dysfunction Biliary Complications “The Achilles heel of liver transplantation”

23. Post LT Cholangiopathy

24. Disease Recurrence post transplant • HCV 100% 30% cirrhotic at 5 years • HBV 100% without prophylaxis • AIH/PBC/PSC 20% • NASH Up to 80% • Cholangiocarcinoma • HCC dependant on tumor size • Hemochromatosis

25. Primary Diseases of Recipients

26. Patient Survival Survival (%) Years post transplant

27. Causes of Death ANZLT registry 2006.

28. Q & A • Orthotopic liver transplantation: a. better prognosis in adults than children b. contraindicated in cholangiocarcinoma c. liver not viable >12 hr after harvesting d. external biliary drainage influences cyclosporin dosage e. outcome of Tx is independent of stage of liver disease

29. Q & A • A patient presents with hepatitis. ALT 3500 • The least likely diagnosis a. panadol od b. alcohol c. Budd Chiari d. viral hepatitis e. ischaemic hepatitis

30. Q & A • What is the best predictor for oesophageal variceal bleeding?A. portal venous pressureB. Child Pugh ScoreC. Variceal sizeD. INR

31. Q & A • Female diacharged home after hemicolectomy. Husband brings her back 48 hours later with abdominal pain, jaundice, and anemia. What is the strongest predictor of increased mortality without liver transplant?A. raised bilirubinB. raised creatininec. Raised ASTd. Raised ALTe. PT 160

32. Q & A • 50 year old man with chronic liver disease with heaptitis B infection. Recent gastroscopy shows large oesophageal varicies. Alb 32 platelets 70 AFP 300 INR 1.4CT shows localised mass in liverWhat is the best treatment/management?A. ChemoembolisationB. Liver transplantC. RFAD. CryotherapyE. local rescetion