Liver Transplantation Liver Transplantation for for Alcoholic Liver Alcoholic Liver Disease Disease Liver Liver Transplantatio Transplantatio n n David Orr Hepatologist NZLTU
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