LIVER FAILURE

MEDICAL ASPECTS OF
LIVER TRANSPLANTATION

Prof. Dr. P. Michielsen

1st Master in Medicine
2016-2017
 acuut komen in bepaalde omstandigheden in aanmerking bij Tx via een speciale prcedure
bij chronisch leverfalen komen pt in aanmerking via de gewone procedure en MELT score
daarom moet je oppassen dat het niet als een acute aan je gepresenteerd wordt terwijl het een
chronische is om een speciale procedure te krijgen

Liver failure
Loss of functional liver mass below critical
threshold
- *Acute liver failure
- *Acute on chronic liver failure: decompensation
(due to sepsis, bleeding…) in a patient with pre-
existing chronic liver disease
- Chronic liver failure: decompensation due to
progression underlying chronic liver disease

* Potentially reversible

1
 Acute liver failure
Deze eerste drie zijn de typische kenmerken die altijd aanwezig moeten zijn

• Fast deterioration liver function

• Disturbances of consciousness
• Coagulation disorder (INR ≥ 1,5)
• No prior liver disease
• Disease duration < 26 weeks

2
Acute liver failure: symptoms
• Jaundice
• Coagulation disturbances
• Rapidly progressive HE,
leading to cerebral edema
and cerebral herniation

Geen tekens chronisch leverlijden, algemene

toestand goed is, slechte stollingsparameters en
snel een …. optreedt. Risico op cerebraal
oedeem en hersen herniatie

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Acute liver failure
Liver coma

4
Interval between development of jaundice
and of hepatic encephalopathy
King’s College, London
• < 7 d: Hyperacute liver failure
• 8-28 d: Acute liver failure
• 5-12 wk: Subacute liver failure
Heel wat classificaties
die je niet van buiten
moet kennen
ze worden door mekaar
gebruikt
De engelse Kings
collage.
Hoe korter het interval

Better prognosis when interval short (e.g.

paracetamol intoxication) compared to
subacute liver failure (e.g. idiosyncratic drug
toxicity)

5
 Acute liver failure
Causes
• Viral hepatitis (A, B, E)
• Hepatotoxicity bv paracatamol intoxicatie
• Metabolic (Acute fatty liver of pregnancy, Wilson, Reye)
• Ischemia (Budd-Chiari, shock)
• Massive malignant infiltration
• Severe bacterial infection
• 20% unknown

6
=paracetamol

7
 Acute liver failure
Management
• Admission IC unit, follow up coma scale
• Monitoring vital functions, correction electrolyte
disorders, administration hypertonic glucose
• Lactulose (HE)
• Mannitol in case of cerebral oedema
• Specific treatment: N-acetylcysteine in
paracetamol intoxication
• Consider LTX if patient fulfills prognostic criteria
(Clichy/King’s College) based on HE, coagulation,
bilirubin, creatinine

14
 Acute liver failure
Prognostic models
niet van buiten kennen

Clichy
 30 y > 30 y

Factor V (%) < 20 < 30

kun je niet in alle centra bepalen

Encefalopathy (grade) 3/4 3/4

15
 Acute liver failure
Prognostic models
King’s College criteria for HU LTX
Paracetamol intoxication
• Consider LTX when arterial lactate > 3.5 mmol/L
after early volume resuscitation, or
• Listing for LTX when
- Art. pH < 7.3 independent of HE or
- Arterial lactate > 3.0 mmol/L after volume
resuscitation independent of HE, or
- In absence of above, all following three
• PT > 100 s (INR ≥6.5)
• Creatinine > 3.4 mg/dL
• Encephalopathy gr 3 of 4

16
 Acute liver failure
Prognostic models
King’s College criteria HU LTX
Other causes
- PT > 100 s (INR ≥ 6.5) independent of HE
- In absence of above, 3 of following criteria:
• Etiology (NANB, halothane, drug toxicity)
• Age <10 or >40 y
• PT > 50 s (INR > 3.5)
• Bilirubin > 17.5 mg/dL
• Interval between jaundice and HE > 7 d

17
 Validation prognostic scores ALF
• Positive predictive value (observed mortality in
patients predicted to die)
- King’s College criteria paracetamol: 80%
- King’s College criteria non-paracetamol: 70-90%
• Negative predictive value (observed survival
in patients predicted to survive)
- King’s College criteria paracetamol: 70-90%
- King’s College criteria non-paracetamol: 25-50%

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 Liver transplantation
Indications
• Terminal acute or chronic liver disease
- Acute liver failure
- End stage chronic liver disease
• Primary, non-resectable liver tumours of limited
extent in esseintie HCC

• Metabolic disease with primary defect in the liver

- In absence of other therapeutic options

- In absence of absolute contra-indications

21
 Indications for LTX
• Chronic, non-cholestatic liver diseases
- Chronic hepatitis C
- Chronic hepatitis B
- Auto-immune hepatitis
- Alcoholic liver disease
- NASH, cryptogenic cirrhosis
• Cholestatic liver diseases
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- Pediatric cholestatic liver diseases

22
 Indications for LTX
• Metabolic diseases causing cirrhosis
- Hereditary hemochromatosis
- Alfa-1 antitrypsin deficiency
- Wilson’s disease
- …
• Metabolic diseases with severe extrahepatic
morbidity
- Familial amyloid polyneuropathy
- Hyperoxaluria type 1
- …

23
 Indications for LTX
• Liver tumours
- Hepatocellular carcinoma
- Levermetastases neuro-endocrine tumours
- Polycystic liver soms als het compliceerd (besmetting, portale hypertensie)
- …
• Acute liver failure
• Others
- Budd-Chiari syndrome
- Caroli syndrome
- …
• Retransplantation 10% zijn retransplantaties (bv door re-infectie HepC)

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ELTR 2017

25
ELTR 2017

alcoholische cirrose

= cholangitis

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 Absolute contra-indications
• Extrahepatic malignancy (except spinocellular
skin carcinoma): 2 years after curative
treatment
• Advanced cardiopulmonary disease excluding
major surgery
• Cholangiocarcinoma (in most centres), except
clinical protocols
• Systemic extrahepatic infection
• Irreversible multi-organ failure
• Irreversible brain damage
27
When is LTX for alcoholic cirrhosis
appropriate?
1. Never, because of shortage of organs?
2. After 5 years abstinence? Andere verslavingen nagaan
Psychiatrisch advies vragen we

3. After 1 years abstinence?

aan —> beoordeling verslaving
Sociale situatie pt en sociale
dienst inschakelen voor

4. After 6 months abstinence?

ondersteuning te beoordelen

5. If the patient solemny promises to stop

drinking?

28
 LTX for alcoholic liver disease

• Pre-LTX: cave extrahepatic disease related to

alcohol or smoking
• Favourable psychiatric evaluation by
‘addictiologist’
• Compliance, social integration, importance of
support from the patient’s environment!
• Most centres: abstinencre of 3-6 months
(assessment possibility of recovery and
evaluation abstinence)

29
 LTX in HIV + patients?
1. Always excluded?
2. Acceptable under certain conditions?
3. To be considered as all other patients?

32
 LTX and HIV
Consensus Lyon, 2005
• HIV patients are candidates for LTX in the
same indications on condition
- Stable HIV infection (undetectable HIV RNA,
independently of CD4 count)
- No history opportunistic infections defining AIDS,
except before HAART era
- Absence of general contra-indications (screening for
malignant tumours!)
• Precaution: beware drug interactions calcineurin
inhibitors and protease-inhibitors!

33
 LTX and viral hepatitis
• HBV
- HBV DNA: to be suppressed as low as possibe
prior to LTX (nucleos/tide-analogues)
- Post transplantation: HBIG in anhepatic phase,
life long HBIG (titer anti-HBs > 200 IU/mL (IV or
SC) + nucleoside/tide analogues
dus voor transplantatie met antivirale middelen zorgen dat HBV zo laag mogelijk is
• HCV dan post transplantatie hoge hoeveelheden HBIG en dan levenslag nog geven in combinatie met antivirale middlen
regelmatig titer antistof meten. De surfica antigeen wordt negatief en antistoffen proberen we boven 200 te houden
- DAA era: possibility of elimination HCV
kan door behandeling soms zelfs transplantatie
pretransplant vermeden worden
door verbetering leverfunctie door behandeling
• Beware: ‘MELD purgatory’ Hep C heeft soms tot gevolg dat de wachttijd
langer wordt

- When HCV RNA positive at LTX: 100% recurrence

- Possibility of treatment with DAA’s after LTX

34
 Which of following cases is eligible
for LTX?
• Case 1:
Male, 65 yo, cirrhosis due to
hemochromatosis, 8 cm HCC in segments
VII/VIII
upper limit ligt op 5 cm: Milaan criteria voor risico op recidief

• Case 2: Dus casus 2 heeft een betere prognose

Female, 40 yo, alcoholic cirrhosis, alcohol use
stopped since 1 year, recurrent hepatic
encephalopathy and ascites (Child-Pugh 12)

35
 Relative contra-indications
• Age > 65 y Relatief: nu wel tot 75 jaar
• Active abuse of alcohol or drugs (6 months stop rule)
• Severe psychiatric disease
• Incapacity of the patient to judge the risk of the
procedure or to meet the requirements
• Active hepatitis B replication
• Total occlusion portal venous system
• Reduced cardiovascular or pulmonary functions
increasing the surgical risk
• HIV positivity
• Obesity (BMI > 35) ook size matching: lever ook groter bij dikkere mensen
• Other systemic disorders unfavourably influencing
prognosis

36
 Selection procedure
• Chronic liver diseases
- MELD score
- Effect specific complications on survival
(‘Standard exceptions’ and ‘Non-standard
exceptions’)
• Acute liver failure
- Clichy criteria
- King’s College criteria

37
 Criteria for listing
• Diagnosis of a condition accepted for LTX
• Predicted 1 year survival chance <90%, or
poor quality of life
• Absence validated alternative treatment
options
• Absence absolute contra-indications

41
 Minimal listing criteria

• Child-Pugh score ≥7 or MELD ≥ 10

• Major complications: ascites, variceal
bleeding, hepatic encephalopathy,
spontaneous bacterial peritonitis
• Patients with hepatorenal syndrome
type 1 should be referred with priority

42
 Limits for LTX
• Acute liver failure
- Irreversible brainstem damage (loss
oculovestibular reflexes, reduced cerebral
perfusion pressure)
- Dependence on vasopressors
• Chronic liver disease
- Child C with multiple organ failure

43
 Evaluation prior to LTX
• Evaluation liver function
• Evaluation vascularisation of the liver
• Screening for possible sources of infection
• Evaluation cardiovascular en pulmonary
function
• Psychosocial evaluation

44
 Wait time on the
liver transplant list
Eurotransplant: Benelux, Germany, Austria, Slovenia,
Croatia, Hungary

• Urgency code
• MELD score
• Body weight
• Blood group
• Region (Belgium is 1 region in Eurotransplant):
donor rate!
diabetische voet is een contra-indicatie omdat de infectie niet gaat verbeteren porst transplant endie dieper gaaat.
geldt ook voor andere extra-hepatische infectie die niet onder controle is

45
 Liver allocation Eurotransplant
since 16.12.2006
1. High urgencies (HU)
2. Accepted combined organ transplantation
(ACO)
3. Transplantable patients (T)
• Lab MELD (score based on INR, bilirubin,
creatinine)
• Exceptional MELD: MELD score standard (SE)
and non-standard exceptions (NSE)

46
 Immune suppression
post LTX
• Steroids
- Mostly 3 months
• Calcineurin-inhibitors (cyclosporine,
tacrolimus)
- Side effects: neurotoxicity, nephrotoxicity,
hypertension, diabetes
• Mycophenolate mofetyl
- Side effects: bone marrow suppression, GI tract
complaints
• m-TOR inhibitors (sirolimus, everolimus)
- Side effects: GI tract complaints, dyslipidemia,
bone marrow suppression, delayed wound healing
dus we wachten daar een aantal weken mee voordat we deze geven

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ELTR 2017

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ELTR 2017

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