Acute liver failure differences between children and adults

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Acute liver failure differences between children
and adults

• Anil Dhawan MD FRCPCH
• Paediatric Liver Centre
• Kings College Hospital
• London

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Are children small adults !
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Acute liver failureChildren vs Adults

• Definition
• Aetiology
• Diagnostic difficulties
• Contraindications to Liver transplantation
• Prognostic criteria

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Acute Liver Failure
Definition
Massive liver necrosis with encephalopathy
developing within 8 weeks from the first signs of
illness in a patient without underlying chronic
liver disease Troy and
Davidson
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Acute liver failure
Encephalopathy

• late event
• difficult to diagnose in very young children and
  particularly in infants

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Complications
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51
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Acute liver failure
Definition
Multisystem disorder in which severe acute
impairment of liver function with or without
encephalopathy occurs in association with
hepatocellular necrosis in a patient with no
recognised underlying chronic liver disease
Bhaduri and Mieli-Vergani
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Aetiology of ALF in adults
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331 Pediatric Patients with ALF
APAP
Unknown
Drug
Hepatitis A
Viral (not B)
Shock
Autoimme Hep.
Wilsons
Metabolic
Other
PALFSG Data Set
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Aetiology of ALF in childrenKCH datan236
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Acute liver failure in childhood
Diagnostic Difficulties
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Disorders not cured by transplantation

• Mitochondrial disorders with neurological
  involvement
• Niemann-Pick disease type C
• Giant-cell hepatitis with Coombs positive
  haemolytic anaemia
• Haemophagocytic lymphohistiocytosis
• Leukaemia - Lymphoma

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Acute Liver FailureBone Marrow Exam

• Exclude-
• HLH
• Leukaemia
• Lymphoma
• Storage disorders
• Mitochondrial Disorders

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HLH
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Leukaemia
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Nieman Pick Disease
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Pearsons Syndrome
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Value of liver biopsy
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LT for neonatal hemachromatosis
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Neonatal Haemochromatosis
Kings 1990 - 2002
Surgical management Liver transplantation

• 15 listed

• 10 transplanted
• (median age 18.5 days, range 5-42)

• 5 alive well
• (median follow up 3.6 years, range 0.5-7.6)

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High dose immunoglobulin during pregnancy for
recurrent NNH WhitingtonHibbard Lancet 2004

• Methods-
• Women whose most recent pregnancy ended in NNH
• 1g/kg IVIG, weekly from 18th wk to end of
  gestation
• Results-
• 16 pregnancies, all live births, normal exam and
  AGA
• 12 babies evidence of NNH
• All survived with medical or no treatment

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High dose immunoglobulin during pregnancy for
recurrent NNH WhitingtonHibbard Lancet 2004

• Conclusions-
• Treatment with IVIG modified recurrent
  NNH (not lethal to fetus or neonate)
• Support an alloimmune mechanism for recurrent
  NNH
• May be a preventable cause of ALF !

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MITOCHONDRIA
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PRESENTATION

• n 24
• Age at presentation
• 7.5 months (birth - 60 months)
• Mode of presentation
• acute liver failure (10/24)
• liver dysfunction (12/24)
• jaundice/organomegaly ( 2/24 )

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Liver Transplantation for Mitochondrial
Cytopathies

• n3/24
• 1 death , 10 months post transplant
• 1 stable , 3 years post surgery
• 1 LT in infancy (her sib died), developed
  myoclonic epilepsy, dg on muscle bx 14 y after
  LT, well

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Acute liver failure in childhood
When to list for transplant?
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Prognosis -ALF

• KCH criteria
• Factor V (lt20 , age lt 30 yrs) French
• (Validated in UK not discriminatory in
  Paracetamol OD)
• Histological assessment of viable hepatocytes
  (lt25 poor prognosis)
• (sampling error)
• CT scan (size and functional reserve) Japan
• Serial USS (subjective, subacute liver failure)
• Serial AKBR (predicts likely survivors)
• (academic)

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Patients Dhawan et al Ped Trans (2004)

• Retrospective review 1983 - 1994
• N 103
• 55 male
• Median age 3.13 years range 3 days 15.98 years

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Outcome

• Alive n 24
• Dead n 43
• Transplanted n 36

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Development of prognostic tool

• Univariate analysis, cross tabulation and ANOVA
• Multivariate logistic regression to develop a
  predictive model
• ROC curve to determine cut-off values

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Haematological factors
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Liver function test
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ROC predictors of mortality for ALF
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Prognostic indicators of outcome
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ALF and Wilsons diseasePrognostic
Criterian57Died 15Alive without Tx
32 -Dhawan et al Liver Transplantation
2005 - highlight in Nature current Practice
2005
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Wilsons Disease Outcome Score at Presentation
(Nazer et al, 1986)
PT converted to INR
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Predictive Value of Mortality
LR
NPV
PPV
Specificity
Sensitivity
Score
4.2
97
56
78
93
³ 5
6.7
98
67
86
93
³ 6
8.7
96
72
90
87
³ 7
18.3
92
85
96
73
³ 8
33.3
91
91
98
67
³ 9
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ROC predictors of mortality from Wilsons Disease
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New Wilsons Index
Albumin (g/l)
WCC (109/l)
AST (IU/l)
INR
Bilirubin (mmol/l)
Score
gt45
0 6.7
0 - 100
0 1.29
0 - 100
0
34 44
6.8 8.3
101 150
1.3 1.6
101 150
1
25 33
8.4 10.3
151 200
1.7 1.9
151 200
2
21 24
10.4 15.3
201 300
2.0 2.4
201 300
3
0 20
gt 15.4
gt 301
gt 2.5
gt 301
4
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Wilsons Index Predictive Value
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Conclusions

• Encephalopathy not central to definition
• Different aetiology
• Diagnostic difficulties
• Prognostic criteria

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Children are not small adults
5 days
5 years