9. Treatment of Amatoxin Poisoning-20 year retrospective analysis

736
time between appearance of jaundice and onset of
encephalopathy, and bilirubin concentration. The criteria
have been recently evaluated by the University of
Pittsburgh for 177 patients over a 13-year period and
were found to be relatively effective in predicting death
and the need for transplantation. [406] French emergency
liver units rely on the combination of encephalopathy
stages (III and IV) with factor V concentration and
age. [407 – 409] Other prognostic models reviewed by Mas
and Rodés [244] based on hemodynamic disturbances and
clinical course of FHF have also been developed.
Furthermore, other variables such as a factor VIII/V
ratio [410] as well as serial a-fetoprotein levels [245] might
be useful tests for predicting survival in FHF. Lastly, a
Gc level ,34 mg/mL 48 hours after admission strongly
suggests a stage of liver failure beyond which recovery
will not occur. [411]
Despite the lack of absolute predictors, prognostic
factors such as stage of encephalopathy, coagulation
tests, metabolic abnormalities, and age are useful in the
rational planning of LT. Of 31 transplanted patients
having undertaken OLT (including 4 children below 10
years of age), the prognostic factors used for 27 cases are
listed in Table 7.
Encephalopathy Stages
The association between encephalopathy stages
(I–IV) [412] and vital prognosis is controversial. According
to Bernuau et al. [413] and Frohburg et al., [399]
encephalopathy does not always reflect liver function
deterioration. Since advanced encephalopathy typically
occurs late in the course of the FHF, the stage of
encephalopathy may be of limited use. [403] Other authors
promote encephalopathy stage as the most powerful
clinical indicator of the severity of liver disease.
[244,409,414,415] According to Gill and Sterling, [245]
patients with a stage II encephalopathy have a mortality
of 30% while those who progress to stage IV have a
mortality rate greater than 80%. In the early use of OLT
for amatoxin poisoning, encephalopathy stages (III and
IV) were the major decision factors for this surgery.
[80,103,106,136,154,193,199]
However, Klein’s experience [102] indicated a clinical
course of amatoxin poisoning characterized by slow
deterioration over a week that then worsens quickly. This
pattern may lead to an early underestimation of liver
damage. Consequently, several authors think that LT
should be considered with the onset of mild encephalopathy
(stages I and II) before the onset of progressive and
MARCEL DEKKER, INC. 270 MADISON AVENUE NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
profound neurological signs resulting from severe
amatoxin intoxication [86,156,198,199] (Table 7).
Coagulation Factors
No definitive conclusion can be drawn about the
usefulness of the degree of coagulopathy as an indication
for LT because too few patients are included in clinical
data, and prophylactic administration of fresh frozen
plasma modifies or prevents interpretation of coagulation
factors. [401] The PT is considered the most satisfactory
test of hepatocellular necrosis and prognosis. [405,414,415]
Some authors suggest that factor V level is more sensitive
and reliable than PT and a better indicator of recovery
than other biological factors. [158,407,416,417] According to
Izumi et al., [418] the predictive accuracy of plasma factor
V is less than that of international normalized result
(INR) as advocated by Harrison et al. [419] A factor VIII/V
ratio of more than 30% can be associated with a poor
prognosis. [410] The dynamics of a biological marker
could be of greater predictive value than the minimum or
maximum level of the variable itself. The progressive
prolongation of PT was noted as an outcome predictor of
the patients with FHF and its evolution over 4 days after
the poisonous mushroom meal was suggested as a
reliable indicator of recovery or death. [14]
Metabolic Abnormalities
Enjalbert et al.
Metabolic abnormalities such as lactic acidosis,
hypoglycemia, hyperbilirubinemia, and increased aminotransferases
seen in FHF may also provide foundation
for LT decisions. [244] Lactic acidosis and hypoglycemia
are cited as prognostic factors associated with encephalopathy
stage II and prolonged PT that determine urgent
LT. [99,151,156,199] Several studies have shown that a high
level of bilirubin (.300 mmol/L) is a sign of fatal
prognosis. [399,405,420] On the basis of their own
experience, Faulstich and Zilker [14] suggested that LT
be performed when an amatoxin poisoned patient
exhibits a PT below 20% associated with both high
bilirubin and creatinine (.5 and .2 mg/dL, respectively),
on day 3. Patients with progressive failure have
continued rise in the bilirubin and prolongation of PT
despite declining aminotransferases. [245] Recent results
support the hypothesis that a sustained elevation in
markers of regeneration (a-fetoprotein, g-glutamyl
transferase) for more than 10–12 hours combined with
a similarly maintained decline in markers of necrosis
(ASAT, ALAT, alkaline phosphatase, LDH) levels could
aid in prediction of recovery. [124]