Liver Transplantation Liver Transplantation for for Alcoholic Liver DiseaseAlcoholic Liver DiseaseLiver Liver

TransplantatioTransplantation n

David Orr

Hepatologist

NZLTU

Milestones in TransplantationMilestones in Transplantation

19481948 ACTH and CorticosteroidsACTH and Corticosteroids 19531953 6-mercaptopurine6-mercaptopurine 19571957 Kidney Transplantation (Murray)Kidney Transplantation (Murray) 19631963 Liver Transplantation (Starzl)Liver Transplantation (Starzl) 19671967 Successful Liver Transplanatation (Starzl)Successful Liver Transplanatation (Starzl) 19791979 Cyclosporine (Calne)Cyclosporine (Calne) 19821982 50% 1 year survival (Calne)50% 1 year survival (Calne) 19881988 Living Related Liver transplant (Raia)Living Related Liver transplant (Raia) 19941994 Living donor R lobe (Yamaoka)Living donor R lobe (Yamaoka) 19971997 Monosegmental Liver transplants (Rela)Monosegmental Liver transplants (Rela)

Indications For LTIndications For LT

Acute hepatic failureAcute hepatic failure Early graft failure (PGNF, HAT)Early graft failure (PGNF, HAT) Late graft failure (CR, biliary cirrhosis, HAT, Late graft failure (CR, biliary cirrhosis, HAT,

recurrent disease)recurrent disease) Chronic Liver diseaseChronic Liver disease CPS>9 Severe bone disease (esp PBC/PSC)CPS>9 Severe bone disease (esp PBC/PSC) Uncontrolled variceal bleeding Hepatopulmonary syndromeUncontrolled variceal bleeding Hepatopulmonary syndrome Diuretic resistant ascites Portopulmonary hypertensionDiuretic resistant ascites Portopulmonary hypertension Chronic hepatic encephalopathy Hepatorenal syndromeChronic hepatic encephalopathy Hepatorenal syndrome SBP HCCSBP HCC Severe malnutrition Intractable pruritisSevere malnutrition Intractable pruritis Metabolic liver diseaseMetabolic liver disease

Acute Liver FailureAcute Liver Failure

Paracetamol Listing CriteriaParacetamol Listing Criteria (Poor prognosis criteria: survival <5%)(Poor prognosis criteria: survival <5%)

pH < 7.3 (after fluid resus)pH < 7.3 (after fluid resus) OrOr Grade III – IV HEGrade III – IV HE INR > 8INR > 8 Serum Cr > 300Serum Cr > 300

Acute Liver FailureAcute Liver Failure

Non ParacetamolNon Paracetamol INR > 8 (irrespective of HE grade)INR > 8 (irrespective of HE grade) OrOr 3 of 5 Criteria3 of 5 Criteria 1. INR > 41. INR > 4 2. Age < 10 or >402. Age < 10 or >40 3. Aetiology: Drug induced or Non-A, 3. Aetiology: Drug induced or Non-A,

Non-BNon-B 4. Bilirubin > 3004. Bilirubin > 300 5. Jaundice to encephalopathy > 7 days5. Jaundice to encephalopathy > 7 days

Acute Liver FailureAcute Liver Failure

Aetiology Aetiology

Viral: Hep A, B, EViral: Hep A, B, E

(Rare: HSV, EBV, CMV)(Rare: HSV, EBV, CMV)

Drug: Paracetamol, Isoniazid/rifampicin,Drug: Paracetamol, Isoniazid/rifampicin,

NSAIDs, Valproate, carbamazepine, NSAIDs, Valproate, carbamazepine,

Ecstasy, anaesthetic, phenytoin, Ecstasy, anaesthetic, phenytoin,

MAOIs MAOIs

Acute Liver FailureAcute Liver Failure

AetiologyAetiology -AFLP, HELLP-AFLP, HELLP -Wilson’s: Coombes neg hemolytic -Wilson’s: Coombes neg hemolytic anaemia, KF ringsanaemia, KF rings -Amanita phalloides: severe diarrhoea -Amanita phalloides: severe diarrhoea 5 hr post ingestion, ALF 4-5/75 hr post ingestion, ALF 4-5/7 -AIH -AIH -BCS-BCS -Lymphoma-Lymphoma -Ischaemic hepatitis-Ischaemic hepatitis

Contraindications to LTContraindications to LT

Relative Relative ContraindicationsContraindications

Absolute Absolute ContraindicationsContraindications

Extrahepatic sepsisExtrahepatic sepsis

Mod Pulm-HT (MPAP 35-Mod Pulm-HT (MPAP 35-

50mmHg)50mmHg)

No psychosocial supportNo psychosocial support

Advanced Advanced cardiopulmonarycardiopulmonary

diseasedisease

PSMVTPSMVT

HIVHIV

Age > 75 yearsAge > 75 years

Severe Pulm-HT (MPAP> Severe Pulm-HT (MPAP>

50mmHg)50mmHg)

Substance abuseSubstance abuse

AIDSAIDS

Extrahepatic malignancyExtrahepatic malignancy

CADAVERIC ORGAN CADAVERIC ORGAN DONOR DONOR SHORTAGE SHORTAGE

0

10,000

20,00030,000

40,000

50,000

60,00070,000

80,000

90,000

Waiting List Registrants

Donors

UNOS July 2001

Median Waiting Times: Median Waiting Times: Liver Transplant by Blood TypeLiver Transplant by Blood Type

0

100

200

300

400

500

600

700

800

900

Blood Type A Blood Type B Blood Type O

199519971998

Current Allocation SchemaCurrent Allocation Schema

Severity of Illness (Status) Severity of Illness (Status) Allocation determined by:Allocation determined by:

– Blood TypeBlood Type– Waiting timeWaiting time– SizeSize

Live Donor Liver Transplant

Living related liver transplant Living related liver transplant : Donor requirements: Donor requirements

Unsolicited volunteerUnsolicited volunteer Family member (not necessarily blood Family member (not necessarily blood

relative)relative) No clear medical contra-indicationsNo clear medical contra-indications Size appropriate Size appropriate ABO matchedABO matched Age <50Age <50 Normal liver, HIV negativeNormal liver, HIV negative

Donor problemsDonor problems

Biliary complications Biliary complications 6%6% Re-operation Re-operation 5%5% Death <0.3%Death <0.3%

Mean ICU Stay Mean ICU Stay 0.5 days0.5 days Hospital Stay Hospital Stay 6.4 days6.4 days

Brown et al. AASLD 2001

Recipient IssuesRecipient Issues

Retransplant rateRetransplant rate 2.5%2.5% Acute liver FailureAcute liver Failure 2%2% Biliary complicationsBiliary complications 23%23% Arterial complicationsArterial complications 8%8%

Brown et al. AASLD 2001

Common Problems after Common Problems after LTLT

DiabetesDiabetes NODM 15% NODM 15%

Osteoporosis Increased risk in cholestatic liver Osteoporosis Increased risk in cholestatic liver diseases, long term steroids diseases, long term steroids

ObesityObesity

Hypertension CNI Hypertension CNI

Hyperlipidemia SirolimusHyperlipidemia Sirolimus

Neurological Headache- CNI Neurological Headache- CNI

Hematological Anaemia. HCV related Hematological Anaemia. HCV related

Viruses CMV, EBV, Herpes viruses Viruses CMV, EBV, Herpes viruses

MalignancyMalignancy Skin, all solid tumours, PTLD Skin, all solid tumours, PTLD

Renal FailureRenal Failure CNI CNI

What to watch for within the What to watch for within the

first week first week Hepatic Artery thrombosisHepatic Artery thrombosis Portal Vein thrombosisPortal Vein thrombosis InfectionsInfections Bacterial/Viral/FungalBacterial/Viral/Fungal Drug toxicityDrug toxicity Renal ImpairmentRenal Impairment Acute cellular rejectionAcute cellular rejection

Acute cellular RejectionAcute cellular Rejection

40-50% of recipients within 1st year post 40-50% of recipients within 1st year post transplanttransplant

Mainly in first monthMainly in first month High AST/ALT/Alk phosHigh AST/ALT/Alk phos Peripheral eosinophiliaPeripheral eosinophilia

Diagnose on liver biopsyDiagnose on liver biopsy

Histology ACR

Infection post TransplantInfection post Transplant

Month 1Month 1 Nosocomial infectionNosocomial infection Bacteria and fungiBacteria and fungi 19-28% of patients have bacteremia19-28% of patients have bacteremia Staph, Enterococcus (50-60%)Staph, Enterococcus (50-60%)

Month 2-6Month 2-6 CMVCMV

CMVCMV

HerpesvirusHerpesvirus Highest risk are recipients from CMV mismatch or Highest risk are recipients from CMV mismatch or

Recipients of OKT-3/ThymoglobulinRecipients of OKT-3/Thymoglobulin Without prophyllaxis (oral Valganciclovir), risk of Without prophyllaxis (oral Valganciclovir), risk of

symptomatic disease 64%symptomatic disease 64% Fever, leukopenia, hepatitis in up to 25%Fever, leukopenia, hepatitis in up to 25%

Pneumonitis, GI infectionPneumonitis, GI infection Predisposes: chronic rejection, worse HCV recurrence Predisposes: chronic rejection, worse HCV recurrence

and fungal superinfectionand fungal superinfection Treat with iv Ganciclovir/oral Valganciclovir for 3 Treat with iv Ganciclovir/oral Valganciclovir for 3

monthsmonths

Biliary ComplicationsBiliary Complications “The Achilles heel of liver “The Achilles heel of liver transplantation” transplantation”

Early (< 30 days) Early (< 30 days)

Anastomotic bile leakAnastomotic bile leak

Anastomotic strictureAnastomotic stricture

Bile leak at T tube exitBile leak at T tube exit

Obstruction of T tubeObstruction of T tube

Sphincter of Oddi Sphincter of Oddi dysfunctiondysfunction

Late (> 30 days)Late (> 30 days)

Anastomotic strictureAnastomotic stricture

Nonanastomotic Nonanastomotic stricturesstrictures

Bile leak on T tube Bile leak on T tube removalremoval

Sphincter of Oddi Sphincter of Oddi dysfunctiondysfunction

Post LT CholangiopathyPost LT Cholangiopathy

Disease Recurrence post Disease Recurrence post transplanttransplant

HCVHCV 100% 100%

30% cirrhotic at 5 years30% cirrhotic at 5 years HBVHBV 100% without prophylaxis 100% without prophylaxis AIH/PBC/PSCAIH/PBC/PSC 20% 20% NASHNASH Up to 80% Up to 80% CholangiocarcinomaCholangiocarcinoma HCCHCC dependant on tumor size dependant on tumor size HemochromatosisHemochromatosis

Primary Diseases of RecipientsPrimary Diseases of Recipients

CVH 28% AIH 5% Oth 6%ALF 9% BA 1% Met 6%ALD 12% Crypto 7% PBC 8%PSC 12% HCC 6%

Patient SurvivalPatient Survival

0%10%20%30%40%50%60%70%80%90%

100%

1 3 5 7 9 11 13 15

1985-19891990-19941995-19992000-20042005

Years post transplant

Surv

ival (%

)

Causes of Death

Operative 4% Resp 5%

Cerebrovasc 9% Cardio 9%Gastro 3% Sepsis 19%

Recurrent HCC 10% De novo malignancy 8%Graft failure 24% Misc 9%

ANZLT registry 2006.

Q & AQ & A

Orthotopic liver transplantation:Orthotopic liver transplantation:

a. better prognosis in adults than childrena. better prognosis in adults than childrenb. contraindicated in cholangiocarcinomab. contraindicated in cholangiocarcinomac. liver not viable >12 hr after harvestingc. liver not viable >12 hr after harvestingd. external biliary drainage influences cyclosporin d. external biliary drainage influences cyclosporin dosagedosagee. outcome of Tx is independent of stage of liver e. outcome of Tx is independent of stage of liver diseasedisease

Q & AQ & A

A patient presents with hepatitis. ALT A patient presents with hepatitis. ALT 35003500

The least likely diagnosisThe least likely diagnosis

a. panadol oda. panadol od

b. alcoholb. alcohol

c. Budd Chiaric. Budd Chiari

d. viral hepatitisd. viral hepatitis

e. ischaemic hepatitise. ischaemic hepatitis

Q & AQ & A

What is the best predictor for What is the best predictor for oesophageal variceal bleeding?oesophageal variceal bleeding?  A. portal venous pressureA. portal venous pressureB. Child Pugh ScoreB. Child Pugh ScoreC. Variceal sizeC. Variceal sizeD. INRD. INR

Q & AQ & A

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

Q & AQ & A

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