2008 11 18 Insuffisa..

IS
SE
M
IN
A
IR
ES
IR
Insuffisance hépatique aiguë:
Prise en charge médicale et
chirurgicale
Insuffisance hépatique aiguë (IHA)
IN
A
IR
ES
IR
IS
• Altération majeure et globale des fonctions
hépatiques installée sur un intervalle de temps
court (qques jrs à semaines), sur un foie normal
auparavant
SE
M
• ≠ insuffisance hépatique des maladies
chroniques (« Acute on Chronic »)
Définitions françaises
IR
IS
• IHA sévère: Chute du PTT ou du facteur V <
50% sans encéphalopathie
SE
M
IN
A
IR
ES
• IHA grave: Chute du PTT ou du facteur V < 50%
avec encéphalopathie
– IHA fulminante: intervalle ictèreencéphalopathie < 2 sem
– IHA subfulminante: intervalle ictèreencéphalopathie > 2 sem et < 3 mois
Définitions anglo-saxonnes
ES
IR
IS
• Hyperacute liver failure: ictère encéphalopathie
< 7 jours
SE
M
IN
A
IR
• Acute liver failure: ictère encéphalopathie entre
8 et 28 jours
• Subacute liver failure: ictère encéphalopathie
entre 5 et 12 semaines
ES
IR
A
IN
SE
M
IS
IR
IHA: manifestations cliniques
IR
ES
IR
IS
• Manifestations directement liées aux
lésions hépatiques
SE
M
IN
A
• Manifestations liées aux conséquences de
l’IHA sur les autres organes
• Manifestations liées à la cause
IR
ES
• Ictère presque constant
• Ascite modérée possible
IS
Manifestations directement liées aux
lésions hépatiques
SE
M
IN
A
IR
• Symptômes non spécifiques: asthénie, troubles
digestifs…
• Transaminases ↑, bilirubine ↑
• Facteurs de coagulation: PTT, F V ↓
IHA: manifestations cliniques
IR
ES
IR
IS
• Manifestations directement liées aux
lésions hépatiques
SE
M
IN
A
• Manifestations liées aux conséquences de
l’IHA sur les autres organes
• Manifestations liées à la cause
SE
M
IN
A
IR
ES
IR
IS
IHA: manifestations cliniques
IHA: manifestations cliniques
IR
ES
IR
IS
• Manifestations directement liées aux
lésions hépatiques
SE
M
IN
A
• Manifestations liées aux conséquences de
l’IHA sur les autres organes
• Manifestations liées à la cause
SE
M
IN
A
IR
ES
IR
IS
IHA: causes
Ostapowicz G et al, Ann Int Med 2002;137:947-954
IHA: causes
SE
M
IN
A
IR
ES
IR
IS
• Hépatites virales
hépatotropes
non hépatotropes
• Hépatites médicamenteuses
• Hépatites toxiques
• Ischémie hépatique
• Auto-immunes
• Autres (Budd-Chiari, Wilson…)
• Indéterminées
IR
IR
ES
• When PTT < 50%!!!
IS
When to refer to a Liver
Transplant center?
SE
M
IN
A
• Not waiting encephalopathy to refer!!!
• Too late referral: higher risk of mortality
ES
IR
A
IN
SE
M
IS
IR
IHA: Place du N-acétyl cystéine?
ES
IR
IS
Iv N-acetylcysteine improves spontaneous survival in early stage nonacetaminophen acute liver failure. Lee et al., USA #79
A
IN
ALF Adult patients
848 screened
8 centers / 8y
Primary end point:
-overall survival
IR
NAC
SE
M
Placebo
Etiologies
-HBV 37 (21%)
-drug 45 (26%)
-AIH 26 (15%)
-indeterminate 41(24%)
-others 24 (14%)
Secondary end point:
-transplant-free survival
-transplant rate
NAC
81
IR
n
ES
Clinical and demographic features
7d
SE
M
Coma gr 1-2 Transplant-free
Survival
Coma gr 3-4 transplant-free survival
p
92
NS
0,026
70,4% (57/81)
66,3% (61/92)
0,57
39,5% (32/81)
27,3% (25/92)
0,09
51,7% (30/58)
30,4% (17/56)
0,021
8,7% (2/23)
22,2% (8/36)
0,177
32,1% (26/81)
44,6% (41/92)
0,09
A
Transplant-free survival
IN
Overall survival
placebo
12d
IR
Time from jaundice to coma
Transplant rate
IS
IHA: Place du N-acétyl cystéine?
IR
IS
IHA: Place du N-acétyl cystéine?
ES
Conclusions
SE
M
IN
A
IR
-Patients with early coma grades receiving NAC
showed a significantly higher spontaneous survival
rate
-Taken its good safety, NAC use in early stages of
NAALF can be recommanded
-When advanced intractable ALF is reached,
transplantation may be the only option
SE
M
IN
A
IR
ES
IR
IS
IHA: Traitements spécifiques
SE
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IN
A
IR
ES
IR
IS
IHA: Pronostic
Ostapowicz G et al, Ann Int Med 2002;137:947-954
SE
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IN
A
IR
ES
IR
IS
IHA: Pronostic
Ostapowicz G et al, Ann Int Med 2002;137:947-954
SE
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IN
A
IR
ES
IR
IS
IHA: Transplantation hépatique
SE
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IN
A
IR
ES
IR
IS
IHA: Transplantation hépatique
SE
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IN
A
IR
ES
IR
IS
Transplantation hépatique
hépatectomie totale
transplantation
Hypothèses sur la régénération
hépatique
IS
hépatocytes fonctionnels
IR
ES
IR
100 %
10 - 5 %
?
SE
M
IN
A
?
?
0%
?
encephalopathie
?
mort
temps
SE
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IN
A
IR
ES
IR
IS
IHA: Critères de Transplantation
IHA au paracétamol: Modifications des
critères du King’s College
SE
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IN
A
IR
ES
IR
IS
• Strongly consider transplantation if:
Arterial lactate concentration is above 3.5 mmol/L
after fluid resuscitation
• List for transplantation if:
Arterial PH is below 7.3 or arterial lactate
concentration is above 3.0 after adequate fluid
resuscitation
Or concurrently: (a) serum creatinine is above 300
µmol/L, (b) INR is above 6.5, (c) there is
encephalopathy of grade 3 or greater
Bernal et al, Lancet 2002;359:558-563
ELTR
Primary Diseases leading to Liver 12/2004
Transplantion in Europe
01/1988 - 12/2004
Acute hepatic failure : 4831
6%
9%
IR
IS
Metabolic diseases : 3152
3%
ES
Cholestatic
diseases : 5739
* Others : 1604
SE
M
IN
A
IR
11%
Cancers : 6564
Cirrhosis : 31169
12%
58%
* Others :
Budd Chiari : 526
Parasitic diseases : 52
Benign liver tumors or Polycystic diseases : 555
Other liver diseases : 471
ES
IR
A
IN
SE
M
IS
IR
ELTR
Evolution of Primary Diseases leading12/2004
to Liver Transplantation in Europe
05/1968 - 12/2004
IS
100%
ES
IR
80%
A
IR
60%
SE
M
IN
40%
20%
0%
6880
82
84
86
88
90
Cirrhosis : 32008
Acute hepatic failure : 4978
92
94
96
98
Cancers : 7070
Others : 11122
2000
2002
2004
Primary Diseases leading to Liver Transplantion by Country
01/1988 - 12/2004
AUSTRIA
BELGIUM
CZECH REP.
IS
DENMARK
FINLAND
IR
FRANCE
GERMANY
ES
GREAT BRITAIN
HUNGARY
IR
IRELAND
ITALY
ROMANIA
SLOVENIA
Others : 6491
SE
M
NORWAY
PORTUGAL
Cancers : 6349
IN
NETHERLANDS
POLAND
Acute hepatic failure : 4180
A
MONACO
SPAIN
SWEDEN
SWITZERLAND
TURKEY
YUGOSLAVIA
0%
20%
40%
60%
Cirrhosis : 30720
80%
100%
Primary Diseases leading to Liver
Transplantation in Adult Recipients
IS
01/1988 - 12/2004
ES
IR
>=60 yrs
SE
M
IN
A
IR
45 to 60 yrs
15 to 45 yrs
0%
20%
40%
60%
80%
100%
Cirrhosis : 30720
Cancers : 6349
Acute hepatic failure : 4180
Others : 6491
Patient Survival according to the
Indication
ELTR
12/2004
01/1988 - 12/2004
IS
(%)
100
ES
83
76
78
63
IN
A
IR
72
67
60
IR
Total Log Rank test p = 0.0001
80
66
62
61
58
SE
M
62
40
Cirrhosis : 31090
Cancers : 6547
Acute hepatic failure : 4822
56
54
46
42
p Log Rank :
Acute Hepatic Failure vs Cirrhosis : 0.0001
Cancers vs Cirrhosis : 0.0001
Acute Hepatic Failure vs Cancers : 0.0001 (Wilcoxon test)
20
0
0
1
2
3
4
5
6
7
8
9
10 Yrs
SE
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IN
A
IR
ES
IR
IS
Transplantation hépatique
hépatectomie totale
transplantation
SE
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IN
A
IR
ES
IR
IS
Transplantation
auxiliaire
ES
IR
A
IN
SE
M
IS
IR
SE
M
IN
A
IR
ES
IR
IS
Transplantation auxiliaire
Azoulay D et al: Ann Surg. 2001 Dec;234(6):723-31
+
12
APOLT
IR
=
37
OLTx
APOLT (12)
Whole Liv OLTx (24)
4
6
ES
49 TH
IS
APOLD vs OLTx for acute liver failure:
single center case-control study.
IR
Hospital Mortality
1 ± 1,3
A
Technical complication
3
0
4
2
1 year Patient Survival
66%
66%
1 year reTx free survival
39%
66%
IN
Retransplantation
0,3 ± 0,5
SE
M
Brain death / Edema
2/12 (17%) full success of APOLD; 1 of which with neurologic sequelae!
On an intent-to-treat basis, the efficacy of the APOLT procedure is low. The
indications for an APOLT procedure should be reconsidered …
APOLT = auxiliary partial orthotopic liver transplantation
Lodge JP et al: Ann Surg. 2008 Feb;247(2):238-249
=
13
OLTx
+
13
AOLT
IR
TH
IS
AOLT for Paracetamol acute liver failure
ES
AOLT (13)
4
IR
Hospital Mortality
Whole Liv OLTx (13)
15%
A
Technical complication
IN
Retransplantation
SE
M
Brain death / Edema
3
?
1 year Patient Survival
69%
1 year reTx free survival
61%
8/9 surviving AOLT are OFF-IS with a better quality of life
this new technique is encouraging: 69% actual survival, no long-term IS requirement,
and improved quality of life in the 62% successful cases
AOLT = auxiliary (whole Liver) orthotopic liver transplantation
J+3 mois
J+1 an
SE
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IN
A
IR
ES
IR
IS
J+10
Revue Littérature
1991
1
1
0
Omaha
1997
7
5
1
London
1997
7
2
0
1999
35+12
AOL+AHL
2001
Rennes +
Strasbourg
2002
Clichy
Leeds
IS Free
(%)
0
100
100
1
3 = 43%
57
100
0
3 =43%
43
50
3+3
6
10=21%
71
48
IR
A
IN
SE
M
Villejuif
Survie 1
an (%)
0
Mortalit
é
IS
Hannover
EURALT
Re- PNF ReTH
OP
IR
Pt
ES
anné
12
0
1
3
4=33%
66
25
17
5
1
3
6=35%
65
46
2002
6
0
0
0
1=16%
66
80
2008
13
2
2
3
4=31%
69
100
Auxiliary vs Non Auxiliary Graft Survival
in Urgent Liver Transplantation
01/1988 - 12/2004
(%)
IS
100
Non Auxiliary : 9688
IR
p Log Rank = NS
Auxiliary : 116
IR
ES
80
40
20
45
SE
M
48
IN
52
A
57
60
49
46
43
43
0
0
1
2
3
4
5
6
7
8
9
10 Yrs