Transcript Document

Liver Transplantation
for
Alcoholic Liver
Disease
Liver
Transplantation
David Orr
Hepatologist
NZLTU
Milestones in Transplantation
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1948
1953
1957
1963
1967
1979
1982
1988
1994
1997
ACTH and Corticosteroids
6-mercaptopurine
Kidney Transplantation (Murray)
Liver Transplantation (Starzl)
Successful Liver Transplanatation (Starzl)
Cyclosporine (Calne)
50% 1 year survival (Calne)
Living Related Liver transplant (Raia)
Living donor R lobe (Yamaoka)
Monosegmental Liver transplants (Rela)
Indications For LT
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Acute hepatic failure
Early graft failure (PGNF, HAT)
Late graft failure (CR, biliary cirrhosis, HAT,
recurrent disease)
Chronic Liver disease
CPS>9
Uncontrolled variceal bleeding
Diuretic resistant ascites
Chronic hepatic encephalopathy
SBP
Severe malnutrition
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Metabolic liver disease
Severe bone disease (esp PBC/PSC)
Hepatopulmonary syndrome
Portopulmonary hypertension
Hepatorenal syndrome
HCC
Intractable pruritis
Acute Liver Failure
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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
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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
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Aetiology
Viral: Hep A, B, E
(Rare: HSV, EBV, CMV)
Drug: Paracetamol, Isoniazid/rifampicin,
NSAIDs, Valproate, carbamazepine,
Ecstasy, anaesthetic, phenytoin,
MAOIs
Acute Liver Failure
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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
Extrahepatic sepsis
Mod Pulm-HT (MPAP 3550mmHg)
No psychosocial support
Advanced cardiopulmonary
disease
PSMVT
HIV
Age > 75 years
Absolute
Contraindications
Severe Pulm-HT (MPAP>
50mmHg)
Substance abuse
AIDS
Extrahepatic malignancy
CADAVERIC ORGAN DONOR
SHORTAGE
Donors
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
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90,000
80,000
70,000
60,000
50,000
40,000
30,000
20,000
10,000
0
Waiting List
Registrants
UNOS July 2001
Median Waiting Times:
Liver Transplant by Blood Type
900
800
700
600
1995
1997
1998
500
400
300
200
100
0
Blood Type A
Blood Type B
Blood Type O
Current Allocation Schema
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Severity of Illness (Status)
Allocation determined by:
– Blood Type
– Waiting time
– Size
Live Donor Liver Transplant
Living related liver transplant
: Donor requirements
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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
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Biliary complications
Re-operation
Death
Mean ICU Stay
Hospital Stay
6%
5%
<0.3%
0.5 days
6.4 days
Brown et al. AASLD 2001
Recipient Issues
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Retransplant rate
Acute liver Failure2%
Biliary complications
Arterial complications
2.5%
23%
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
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Hepatic Artery thrombosis
Portal Vein thrombosis
Infections
Bacterial/Viral/Fungal
Drug toxicity
Renal Impairment
Acute cellular rejection
Acute cellular Rejection
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40-50% of recipients within 1st year post transplant
Mainly in first month
High AST/ALT/Alk phos
Peripheral eosinophilia
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Diagnose on liver biopsy
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Histology ACR
Infection post Transplant
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Month 1
Nosocomial infection
Bacteria and fungi
19-28% of patients have bacteremia
Staph, Enterococcus (50-60%)
Month 2-6
CMV
CMV
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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”
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Early (< 30 days)
Anastomotic bile leak
Anastomotic stricture
Bile leak at T tube exit
Obstruction of T tube
Sphincter of Oddi
dysfunction
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Late (> 30 days)
Anastomotic stricture
Nonanastomotic strictures
Bile leak on T tube
removal
Sphincter of Oddi
dysfunction
Post LT Cholangiopathy
Disease Recurrence post transplant
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HCV
100%
30% cirrhotic at 5 years
100% without prophylaxis
20%
Up to 80%
HBV
AIH/PBC/PSC
NASH
Cholangiocarcinoma
HCC
dependant on tumor size
Hemochromatosis
Primary Diseases of Recipients
CVH 28%
ALF 9%
ALD 12%
PSC 12%
AIH 5%
BA 1%
Crypto 7%
HCC 6%
Oth 6%
Met 6%
PBC 8%
Patient Survival
Survival (%)
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
1985-1989
1990-1994
1995-1999
2000-2004
2005
1
3
5
7
9
11
Years post transplant
13
15
Causes of Death
Operative 4%
Cerebrovasc 9%
Gastro 3%
Recurrent HCC 10%
Graft failure 24%
Resp 5%
Cardio 9%
Sepsis 19%
De novo malignancy 8%
Misc 9%
ANZLT registry 2006.
Q&A
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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
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Q&A
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What is the best predictor for
oesophageal variceal bleeding?
A. portal venous pressure
B. Child Pugh Score
C. Variceal size
D. INR
Q&A
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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
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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