Liver Transplantation for Alcoholic Liver Disease David Orr Hepatologist NZLTU

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) 2

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

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

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

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

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

Contraindications to LT Relative Contraindications Absolute Contraindications Extrahepatic sepsis Mod Pulm-HT (MPAP 35- 50mmHg) No psychosocial support Advanced cardiopulmonary disease PSMVT HIV Age > 75 years Severe Pulm-HT (MPAP> Substance abuse AIDS Extrahepatic malignancy

CADAVERIC ORGAN DONOR SHORTAGE Waiting List Registrants Donors UNOS July 2001 3

Median Waiting Times: Liver Transplant by Blood Type

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

Live Donor Liver Transplant 2

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

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

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

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

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

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

Histology ACR

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

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

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

Post LT Cholangiopathy

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

Primary Diseases of Recipients

Patient Survival Survival (%) Years post transplant

Causes of Death ANZLT registry 2006.

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

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

Q & A What is the best predictor for oesophageal variceal bleeding?   A. portal venous pressure B. Child Pugh Score C. Variceal size D. INR

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 bilirubin B. raised creatinine c. Raised AST d. Raised ALT e. PT 160

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 1.4 CT shows localised mass in liver What is the best treatment/management?   A. Chemoembolisation B. Liver transplant C. RFA D. Cryotherapy E. local rescetion