9. Treatment of Amatoxin Poisoning-20 year retrospective analysis

ARTICLE 

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. 

Journal of Toxicology 

CLINICAL TOXICOLOGY 

Vol. 40, No. 6, pp. 715–757, 2002 

Treatment of Amatoxin Poisoning: 

20-Year Retrospective Analysis 

Françoise Enjalbert,* Sylvie Rapior, 

Janine Nouguier-Soulé, Sophie Guillon, 

Noël Amouroux, and Claudine Cabot 

Laboratoire de Botanique, Phytochimie et Mycologie, Faculté de 

Pharmacie, Université Montpellier 1, Montpellier Cedex 5, France; 

Laboratoire de Physique Moléculaire et Structurale, UMR-CNRS 5094, 

Faculté de Pharmacie, 15 avenue Charles Flahault, BP 14 491, 34093 

Montpellier Cedex 5, France; and Centre Anti-Poisons, Hôpital Purpan, 

Place du Docteur Baylac, 31059 Toulouse Cedex, France 

ABSTRACT 

Background: Amatoxin poisoning is a medical emergency characterized by a long 

incubation time lag, gastrointestinal and hepatotoxic phases, coma, and death. This 

mushroom intoxication is ascribed to 35 amatoxin-containing species belonging to 

three genera: Amanita, Galerina, and Lepiota. The major amatoxins, the a-, b-, and 

g-amanitins, are bicyclic octapeptide derivatives that damage the liver and kidney 

via irreversible binding to RNA polymerase II. Methods: The mycology and clinical 

syndrome of amatoxin poisoning are reviewed. Clinical data from 2108 hospitalized 

amatoxin poisoning exposures as reported in the medical literature from North 

America and Europe over the last 20 years were compiled. Preliminary medical 

care, supportive measures, specific treatments used singly or in combination, and 

liver transplantation were characterized. Specific treatments consisted of 

detoxication procedures (e.g., toxin removal from bile and urine, and extracorporeal 

purification) and administration of drugs. Chemotherapy included 

benzylpenicillin or other b-lactam antibiotics, silymarin complex, thioctic acid, 

*Corresponding author. Dr. Françoise Enjalbert, Laboratoire de Botanique, Phytochimie et Mycologie, Faculté de Pharmacie, 

Université Montpellier 1, 15 avenue Charles Flahault, UM 1/CNRS-UPR A 9056, BP 14 491, 34093 Montpellier Cedex 5, France. 

Fax: þ33-467-411-940; E-mail: fenjalbert@ww3.pharma.univ-montp1.fr 

715 

DOI: 10.1081/CLT-120014646 0731-3810 (Print); 1097-9875 (Online) 

Copyright q 2002 by Marcel Dekker, Inc. www.dekker.com

716 

antioxidant drugs, hormones and steroids administered singly, or more usually, in 

combination. Supportive measures alone and 10 specific treatment regimens were 

analyzed relative to mortality. Results: Benzylpenicillin (Penicillin G) alone and in 

association was the most frequently utilized chemotherapy but showed little efficacy. 

No benefit was found for the use of thioctic acid or steroids. Chi-square statistical 

comparison of survivors and dead vs. treated individuals supported silybin, 

administered either as mono-chemotherapy or in drug combination and Nacetylcysteine 

as mono-chemotherapy as the most effective therapeutic modes. 

Future clinical research should focus on confirming the efficacy of silybin, Nacetylcysteine, 

and detoxication procedures. 

Key Words: Amanita; Amatoxins; Galerina; Lepiota; Poisoning; Treatment 

INTRODUCTION 

The hunting and eating of wild higher fungi is a 

traditional activity in many European countries and has 

become an increasingly popular pastime in the United 

States. Despite warnings on the risks of eating wild 

mushrooms, collectors continue to confuse edible and 

toxic species. There are few data defining the number of 

worldwide mushroom exposures; [1 – 11] but poisonings are 

a relatively common medical emergency. Among severe 

mushroom intoxications, the amatoxin syndrome is of 

primary importance because it accounts for about 90% of 

fatality. [12] 

Amatoxin poisoning is characterized by a long 

asymptomatic incubation delay (from 6 to 12 hours) 

and three clinical phases. The first phase, or gastrointestinal 

phase (12–24 hours), consists of cholera-like 

diarrhea, vomiting, abdominal pain, and dehydration. 

During the second phase, or hepatotoxic phase (24– 

48 hours), clinical signs and biochemical evidence of 

hepatic damage leading to a progressive and irreversible 

coagulopathy appear. With the development of hepatorenal 

syndrome (third phase), hemorrhages, convulsions, 

and fulminant hepatic failure (FHF) occur resulting in 

coma and death (4–7 days). Symptoms and clinical 

course of amatoxin-containing mushroom poisoning 

have been thoroughly reported. [13 – 23] Damage to the 

liver is characterized by massive centrilobular necrosis, 

vacuolar degeneration, and a positive acid–phosphatase 

reaction. The kidney shows signs of acute tubular 

necrosis and hyaline casts in the tubules. [24] 

Amatoxin poisoning is caused by mushroom species 

belonging to three genera, Amanita, Galerina, and 

Lepiota [12,25,26] with the majority of lethal mushroom 

exposures attributable to Amanita species. Some 

Amanitas contain two major groups of toxins, amatoxins, 



and phallotoxins. Both are bicyclic peptides composed of 

an amino acid ring bridged by a sulfur atom. The 

chemical structures of nine amatoxins have been 

elucidated as bicyclic octapeptide derivatives; the major 

ones are the a-, b-, and g-amanitins (a-Ama, b-Ama, g- 

Ama). The three amanitins are also present in some 

Galerina and Lepiota species responsible for deceased 

persons. Phallotoxins, detected only in Amanita species, 

have only slight absorption after oral administration and 

should not contribute to amatoxin poisoning. 

Enjalbert et al. 

[27 – 31] 

The molecular mechanism of toxicity has been 

studied in detail. Amatoxins bind with eukaryotic 

DNA-dependent RNA polymerase II, and inhibit the 

elongation essential to transcription. Pharmacokinetic 

studies have shown that amatoxins use the physiological 

transport system for biliary acids to reach the liver, the 

site of irreversible binding to RNA polymerase II. 

Enterohepatic circulation perpetuates high toxin concentration 

in the hepatocytes. [32,33] 

Our survey based on the literature over the last two 

decades lists 2108 detailed cases of amatoxin poisoning 

from North America and Europe. Treatment strategies 

were characterized as preliminary medical care, supportive 

measures, and specific therapies. Specific therapies 

included toxin removal from the digestive, biliary, and 

urinary systems, and blood as well as the administration 

of drugs. Experimental investigations and hypotheses 

concerning the hepatoprotective properties of each 

therapeutic modality justifying its use in human 

amatoxin intoxication were also described. The use of 

liver transplantation (LT) in amatoxin-induced FHF was 

also characterized as a specific therapy among this 

retrospective patient group. 

The aim of this review is a critical analysis of the 

different treatments that were applied to amatoxin 

poisoned patients by determining for each therapeutic

mode its use and its efficacy. Two complementary 

statistical analyses were carried to compare the number 

of survivors and dead for each group of patients, which 

received a particular mode of therapy, liver transplant 

cases being either included as fatalities or excluded from 

each analyzed series. These data enabled a classification 

of therapeutic modalities based on relatively effective, 

ineffective, or unproven asset. 

AMATOXIN-CONTAINING MUSHROOM 

SPECIES 

According to the currently available literature, 

[12,25,26,34] 35 species belonging to the genera 

Amanita, Galerina, and Lepiota contain amatoxins. 

There is agreement on amatoxin-containing Amanita and 

Galerina species but the occurrence of amatoxins in 

some species of Lepiota genus is uncertain. 

In the genus Amanita, the nine amatoxin-containing 

mushrooms are (1) Amanita phalloides (Fr.) Secr. [26] and 

the related species, the so-called “deadly white Amanita 

species,” (2) A. bisporigera Atk., (3) A. decipiens 

(Trimbach) Jacquetant, (4) A. hygroscopica Coker, (5) A. 

ocreata Peck, (6) A. suballiacea Murr., (7) A. tenuifolia 

Murr., (8) A. verna (Bull.:Fr.) Lamarck, and (9) A. virosa 

(Lamarck) Bertillon. [12,25,26,34] A. magnivelaris Peck was 

suspected of containing amatoxins since intoxications 

with a 24-hour latency, liver failure, and hepatic necrosis 

were reported for patients from Guatemala and Rhode 

Island. [35,36] However, amatoxins have never been 

detected in the mushroom tissue. [25,37] 

In the genus Galerina, nine amatoxin-containing 

species are reported: (1) G. autumnalis (Pk.) Sm. and 

Sing., (2) G. badipes (Fr.) Kühn., (3) G. beinrothii Brsky, 

(4) G. fasciculata Hongo, (5) G. helvoliceps (Berk. and 

Curt.) Sing., (6) G. marginata (Batsch) Kühner, (7) G. 

sulciceps (Berk.) Boedjin, [38] (8) G. unicolor (Fr.) Sing., 

[12,26,34,39 – 41] 

and (9) G. venenata A. H. Smith. 

In the mycological literature on Lepiotas, 

[12,25,26,42 – 45] 

24 species are presumed to be amatoxin-producing mushrooms 

and listed alphabetically as follows. The asterisk 

indicates those 16 Lepiota species in which amatoxins 

[46 – 49] 

were detected by thin layer chromatography. 

L. brunneoincarnata Chodat and Martin* 

L. brunneolilacea Bon and Boiffard* 

L. castanea Quélet* 

L. citrophylla (Berk. and Br.) Sacc. 

L. clypeolaria (Bull.:Fr.) Kummer [42] 

L. clypeolarioides Rea* 



Amatoxin Treatment 717 

L. felina (Pers.:Fr.) Karsten* 

L. fulvella Rea* [43] (by semiquantitative Meixner 

test [50,51] ) 

L. fuscovinacea Moeller and Lange 

L. griseovirens Maire* 

L. heimii Locq.* 

L. helveola Bres.* 

L. helveoloides Bon ex Bon and Andary 

L. josserandii Bon and Boiffard* 

L. kuehneri Huijsm. ex Hora* 

L. langei Locq.* 

L. lilacea Bres. [44] 

L. locanensis Espinosa 

L. ochraceofulva Orton* 

L. pseudohelveola Kühner ex Hora* 

L. pseudolilacea Huijsm. [45] 

L. rufescens Lge. [44] 

[47 – 49] 

L. subincarnata Lge.* 

L. xanthophylla Orton* [46] 

Although a-Ama was detected in North American 

Pholiotina (Conocybe) filaris Fr., [52] investigations of 

German collections of this species and other Pholiotinas 

reported the amatoxins neither in the mushrooms nor in 

cases of hepatotoxic poisoning. [12] The available 

information thus identifies 35 species containing 

amatoxins (10 Amanitas, 9 Galerinas, and 16 Lepio- 

[46 – 49,51] 

tas. 

OCCURRENCE OF AMATOXIN 

POISONING 

Amatoxin-containing species and, consequently, 

[53 – 56] 

amatoxin poisonings occur worldwide: Africa, 

America, [25,26,35,57,58] Asia, [46,59 – 66] Europe, [12,67,68] and 

Oceania. [63,69 – 71] Given the few reports of the amatoxin 

syndrome from the African, Asian, and Oceanian 

continents, [55,60,61,69,70,72] our review focused on human 

cases (Tables 1–6) from North American and European 

countries. [73 – 204] The sites include the Canadian 

province Ontario, [97] Mexico, [35,78,84,85] and 21 different 

U.S. states namely Alabama, [89] Arkansas, [93] California, 

[42,74,79,90,93,102,109,119,120,151,193,205 – 207] Florida, [112] 

Georgia, [91,118] Indiana, [132] Kansas, [208] Kentucky, [209] 

Michigan, [108,199,209] Minnesota, [122] Mississippi, [118] 

Missouri, [118,141] New Jersey, [73,139,205,209] New 

York, [93,140,200,206,208] Ohio, [36,207] Oregon, [206,209] Pennsylvania, 

[124] Rhode Island, [36,104,206] Virginia, [208] 

Washington, [207] and Wisconsin [178] as well as 22 

European countries namely Austria, [127,128] Belgium, 

[168,190] Bulgaria, [179,210,211] Croatia, [117] Czech

718 

Republic, [105,157] Denmark, [154,165,202] Finland, [95,106, 

152] France, [75,80,86,103,121,136 – 138,146,148,169,191,192,194 – 

198,212] Germany, [87,88,130,133,155,156,163,164,166,167,201] 

Hungary, [203,204,213] 

Italy, [76,83,92,94,96,100,111,116,125,126, 

131,143 – 145,147,161,176,177,181,185,186] 

the Netherlands, [159] 

Norway, [153] Poland, [99,170 – 173,175,214] Portugal, [162] Slovak 

Republic, [113,114,129,160,180,215] Slovenia, [110,174] 

Spain, [43,50,77,98,115,182 – 184,187 – 189] Sweden, [101,149] 

Switzerland, [158,216,217] Turkey, [81,82,107,134,135,142] and 

United Kingdom. [123] 

The amatoxin poisoning cases found in the literature 

were divided into three groups. The first group comprised 

2108 amatoxin poisoning cases that were adequately 

documented by hospital reports with detailed therapeutic 

information including 32 LTs (Tables 1–6). A second 

[11,36,89,93,97,108,118,199,205 – 

group from North American 

209,218,219] [24,103,111,136,142,160,181, 

and European sources 

212 – 217,220] 

consisted of 169 amatoxin poisonings that 



Table 1 

Amatoxin Poisoning Cases Treated with Supportive Measures Alone with/without Liver Transplant 


Date/Country T/E Cases Mushroom LT Survivors References 

1981 New York 1/3 a.sp 0 1 [73] 

1981 California 1/10 A.ph 0 0 [74] 

1981 California 4/10 a.sp 0 3 [74] 

1982 France 1/1; child G.mar 0 0 [75] 

1982 Italy 2/2 L.bi 0 1 [76] 

1983–1986 Spain 7/85 a.sp 0 7 [43,50] 

1986 Spain 1/3 L.bi 0 1 [77] 

1987 Guatemala 19/19; (children) A.mag 0 11 [35] 

1987 Mexico 8/8; 2 children A.vi 0 6 [78] 

1988 California 4/4 A.ph 0 0 [79] 

1988 France 1/1; child A.ph 1 1 [80] 

1988 Turkey 11/11; 8 children L.hel 0 0 [81] 

1988 Turkey 3/27 L.cas, L.hel 0 2 [82] 

1990 Italy 1/2 L.bi 0 1 [83] 

1990 Mexico 7/7 A.vi 0 2 [84,85] 

1992 France 1/3 L.bi 0 1 [86] 

1992 France 2/3; 1 child L.bi 2 2 [86] 

1992 Germany 2/3 A.ph 0 1 [87] 

1992 Germany 1/3; child A.ph, amat 1 1 [87] 

1994 Germany 9/12 A.ph 0 9 [88] 

1996 Alabama 1/4; child A.ve 0 0 [89] 

1997 California 1/4 a.sp 0 1 [90] 

1997 Georgia 1/1 A.ph 1 1 [91] 

1998 Italy 1/1 A.ph 1 1 [92] 

1999 Arkansas 1/1 A.bis 0 1 [93] 

T/E Cases ¼ treated/exposed individuals; LT ¼ liver transplant; amat ¼ amatoxins in biological fluids; a.sp ¼ amatoxin-containing species; 

A.bis ¼ Amanita bisporigera; A.mag ¼ A. magnivelaris; A.ph ¼ A. phalloides; A.ve ¼ A. verna; A.vi ¼ A. virosa; G.mar ¼ Galerina marginata; 

L.bi ¼ Lepiota brunneoincarnata; L.cas ¼ L. castanea; L.hel ¼ L. helveola; undefined cases are reported in brackets. 

were cited in clinical reports but had no treatment 

information. A third group contained cases of mushroom 

exposures reported only as “cyclopeptide intoxication 

with hepatotoxic effects” and with incomplete clinical 

data. [3 – 9,11,210,211,221] The majority of the cases in the 

second and third groups were either mildly intoxicated or 

asymptomatic individuals who shared the poisoned meal 

and did not necessarily require hospital admission. Only 

the cases in the first group were included in the data 

analysis. 

Of the 35 amatoxin-containing species, 14 were 

responsible for most of the intoxications listed in Tables 

1–6: A. bisporigera, A. magnivelaris, A. ocreata, 

A. phalloides, A. verna, A. virosa, G. autumnalis, [208] 

G. marginata, L. brunneoincarnata, L. brunneolilacea, 

L. castanea, L. fulvella, L. helveola, and L. josserandii. 

The small number of species identified may be an artifact 

of incomplete information; in less than 5% of the

Table 2 

Amatoxin Poisoning Cases Treated with Detoxication Procedures with/without Liver Transplant 

Treatments 

Detoxication 

Date/Country T/E Cases Mushroom Oral C/GA Urin. FD ECP HD–HP/ PL LT Surv. References 




1975–1990 Italy 93/93; children a.sp 0/0 93 0–0/0 0 86 [94] 

1978 Finland 2/2 G.mar 0/0 2 0–0/0 0 2 [95] 

1981 California 3/10 a.sp 3/0 0 0–0/0 0 3 [74] 

1981 Italy 1/1; pregnant A.ph, amat 0/0 1 0–0/1 0 1 [96] 

1982 Canada 1/2 A.bis, A.vi 0/0 0 1–1/1 0 1 [97] 

1982 Canada 1/2 A.vi 0/0 0 1–0/0 0 0 [97] 

1982 Spain 2/8 A.ph 0/0 0 0–0/2 0 2 [98] 

1982–1983 California 11/21 a.sp 11/0 0 0–0/0 0 11 [42] 

1982–1983 California 4/21 A.o, amat 4/0 0 0–0/0 0 4 [42] 

1982–1983 California 1/21; child A.ph, amat 1/0 0 0–0/0 0 1 [42] 

1982–1986 Poland 7/7 A.ph 0/0 0 0–0/7 0 4 [99] 

1982–1991 Italy 2/8; 1 child A.ph 0/0 0 0–0/2 0 1 [100] 

1983–1986 Sweden 93/93 A.ph, A.vi, a.sp, amat 0/0 93 93–93/0 0 93 [101] 

1988 Turkey 3/27; 1 child L.cas, L.hel 3/0 0 0–0/0 0 3 [82] 

1988 Turkey 6/27; children L.cas, L.hel 0/0 0 6–0/0 0 0 [82] 

1989 California 2/2 A.ph 2/2 0 2–0/0 2 2 [102] 

1990 France 1/1 A.ph 0/0 0 1–0/0 1 1 [103] 

1990 Rhode Island 1/1 A.vi 1/0 0 0–0/0 0 0 [104] 

1990–1991 Czech 35/35 A.ph 0/0 0 0–35/0 0 28 [105] 

1990–1991 Czech 38/38 a.sp 0/0 0 0–38/0 0 38 [105] 

1991–1999 Italy 6/8 A.ph 0/0 0 0–0/6 1 6 [100] 

1994 Finland 1/1 A.vi 0/0 0 1–0/0 1 1 [106] 

1994–1995 Turkey 52/60 A.ph 0/0 0 0–52/0 0 52 [107] 

1994–1995 Turkey 8/60 A.ph 0/0 0 8–0/0 0 4 [107] 

1995 Michigan 1/1 A.vi 1/0 0 0–0/0 0 1 [108] 

1996 Alabama 3/4 A.ve 3/0 0 0–0/0 0 3 [89] 

1996–1997 California 2/10 A.ph, a.sp 1/0 0 2–0/0 0 0 [109] 

1997 California 1/4 a.sp 0/0 0 1–0/0 0 0 [90] 

1997 Slovenia 1/1; child a.sp 0/0 1 0–0/1 0 0 [110] 

1998 Italy 2/2 a.sp 0/0 0 2*–2/0 0 2 [111] 

2000 Florida 1/1 a.sp 1/0 0 0–0/0 1 1 [112] 

T/E Cases ¼ treated/exposed individuals; Oral ¼ oral detoxication using C ¼ activated charcoal and GA ¼ gastroduodenal aspiration; Urin. ¼ urinary detoxication by FD ¼ forced diuresis; 

ECP ¼ extra-corporeal detoxication including * ¼ continuous venovenous hemofiltration, HD ¼ hemodialysis, HP ¼ hemoperfusion, and PL ¼ plasmapheresis; LT ¼ liver transplant; 

Surv. ¼ survivors; amat ¼ amatoxins in biological fluids; a.sp ¼ amatoxin-containing species; A.bis ¼ Amanita bisporigera; A.o ¼ A. ocreata; A.ph ¼ A. phalloides; A.ve ¼ A. verna; 

A.vi ¼ A. virosa; G.mar ¼ Galerina marginata; L.cas ¼ Lepiota castanea; L.hel ¼ L. helveola.

720 

Table 3 

Amatoxin Poisoning Cases Treated with Mono-chemotherapy, with/without Detoxication Procedures and with/without Liver Transplant 


Detoxication 

Date/Country T/E Cases Mushroom Drugs Oral C/GA Urin. FD ECP HD–HP/PL LT Surv. References 



1988 Turkey 1/27; child L.cas, L.hel 1ATB 0/0 0 1–0/0 0 0 [82] 

1971–1995 Slovak Republic 103/103; 14 children A.ph, a.sp B.pen 0/0 (FD) (HD–HP)/0 0 95 [113,114] 

1981 Spain 2/2 A.ph B.pen 0/2 0 2–0/0 0 2 [115] 

1982 Spain 6/8 A.ph B.pen 0/0 0 0–0/6 0 5 [98] 

1982–1986 Spain 13/85; 1 child 5 A.ph, 2 A.ve, 3 L.bi, B.pen 2/2 9 0–1/2 0 12 [43,50] 

3 a.sp; amat 

1986 Spain 2/3 L.bi B.pen 0/0 0 0–0/0 0 2 [77] 

1986–1989 Italy 12/12 A.ph B.pen 12/0 0 12–0/0 0 9 [116] 

1988 Croatia 18/18; (children) A.ph B.pen 18/18 18 2–0/16 0 14 [117] 

1991 Ohio 1/1 G.sp B.pen 1/0 0 0–0/0 0 1 [36] 

1994 Missouri 2/2 A.bis B.pen 0/0 0 0–0/0 0 1 [118] 

1996 California 3/3 A.ph B.pen 0/0 0 0–0/0 1 a 

3 [119,120] 

1998 France 1/1 A.ph B.pen 1/0 0 0–0/0 0 1 [121] 

1998 Minnesota 1/1; child A.vi B.pen 1/0 0 0–0/0 0 1 [122] 

1982 U.K. 2/2 A.ph Cimetid 0/0 0 0–2/0 0 0 [123] 

1999 Pennsylvania 1/6 a.sp Cimetid 1/0 0 0–0/0 0 1 [124] 

1987–1993 Italy 86/86 A.ph NAC 86/0 86 0–0/0 0 80 [125] 

1994 Italy 1/1; pregnant A.ph, amat NAC 1/0 1 0–0/1 0 1 [126] 

1996–1997 California 1/10 A.ph NAC 1/0 0 0–0/0 0 1 [109] 

1997 California 1/4 a.sp NAC 1/0 0 0–0/0 0 1 [90] 

1980–1986 Europe 25/252 A.ph, a.sp Silybin 0/0 (FD) (HD–HP)/0 0 24 [127,128] 

1991–1999 Slovak Republic 20/20; (children) A.ph, a.sp Silybin 20/0 20 0–0/0 0 20 [129] 

1993 Germany 26/154 a.sp Silybin 0/0 0 0–0/0 0 26 [130] 

1994 Germany 3/12 A.ph Silybin 0/0 0 0–0/0 3 2 [88] 

1981 California 1/10 A.ph Steroid 0/0 0 0–0/0 0 1 [74] 

1982–1983 California 2/21 a.sp, amat Steroid 2/0 0 0–2/0 0 0 [42] 

1982–1983 California 3/21 a.sp Steroid 3/0 0 0–0/0 0 3 [42] 

1988 Turkey 1/27 L.cas, L.hel Steroid 0/0 0 0–0/0 0 1 [82] 

1997 Italy 1/1 A.ph Steroid 0/0 0 0–0/1 0 1 [131] 

1981 New York 2/3 a.sp Thioc.a 0/0 0 1–0/0 0 2 [73] 

1981 California 1/10 a.sp Thioc.a 0/0 0 0–0/0 0 0 [74] 

1982 Indiana 1/1 A.vi Thioc.a 0/0 0 0–0/0 0 1 [132] 

1982–1986 Spain 4/85; 1 child A.ph, amat Thioc.a 2/3 3 0–2/0 0 4 [43,50] 



ECP ¼ extra-corporeal detoxication including HD ¼ hemodialysis, HP ¼ hemoperfusion, and PL ¼ plasmapheresis; LT ¼ liver transplant; Surv. ¼ survivors; amat ¼ amatoxins in 

biological fluids; undefined cases are reported in brackets. 

Drugs: ATB ¼ antibiotic agent; B.pen ¼ benzylpenicillin; Cimetid ¼ cimetidine; NAC ¼ N-acetylcysteine; Thioc.a ¼ thioctic acid. 

a.sp ¼ amatoxin-containing species; A.bis ¼ Amanita bisporigera; A.ph ¼ A. phalloides; A.ve¼A. verna; A.vi ¼ A. virosa; G.sp ¼ Galerina species; L.bi ¼ Lepiota brunneoincarnata; 

L.cas ¼ L. castanea; L.hel ¼ L. helveola. 

a 

Auxiliary liver transplant.

poisoning cases is the mushroom species actually 

identified. [222] When the species attribution is uncertain 

the onset of clinical symptoms may be a useful indicator 

of potential amatoxin ingestion. 

Amatoxin exposures were more frequently caused by 

A. phalloides in Central and Southern Europe, A. virosa 

in Northern Europe, and A. phalloides and related deadly 

white Amanitas in North America. Unidentified amatoxin-containing 

species caused 21% of poisonings and 

are listed as a.sp. in Tables 1–6. 

STATISTICAL ANALYSIS 

An overall table (189 rows, 12 columns) was 

constituted from Tables 1–6 with the actual or coded 

values of the following parameters: date; country; modes 

of care, number of exposed individuals and treated 

patients; number and percentage of survivors and 

nonsurvivors; mushroom or mixture of mushrooms; 

single drug or drug combination; and LTs. A general 

frequency table was constructed of the observed 

frequencies for each mode of care. Eleven modes of 

care had a sufficient representation for analysis: one 

treatment mode (supportive measures alone, Table 1) and 

10 specific treatments: detoxication procedures (Table 2) 

and nine chemotherapies from Tables 3–6 (monochemotherapies: 

benzylpenicillin, N-acetylcysteine 

(NAC), silybin; bi-chemotherapies: benzylpenicillin/ 

antioxidant drug, b-lactam antibiotic (benzylpenicillin 

or ceftazidime)/silybin, benzylpenicillin/steroid, benzylpenicillin/thioctic 

acid; and tri- and poly-chemotherapies: 

benzylpenicillin combinations with any before 

mentioned drug, with or without silybin). 

Due to small numbers of treated victims, 13 other 

specific chemotherapies were not analyzed: monochemotherapy 

with cimetidine, vitamin C, thioctic acid, 

steroid or antibiotic agent (20 cases from Table 3); and 

bi-, tri-, and poly-chemotherapies with silybin/thioctic 

acid, antibiotic/antiseptic/vitamin C, steroid/thioctic 

acid/vitamin C, antibiotic/thioctic acid/vitamin C, two 

antibiotics/steroid, two antibiotics/NAC, antiseptic/silybin/steroid/vitamin 

C and three antibiotics/steroid (26 

cases from Tables 5 and 6). 

Outcome without surgery for the 32 cases who received 

liver transplant (LT . 0) combined with one or more from 

the 11 analyzed therapeutic modes cannot be known. 

Therefore, in order to assess the effectiveness of the 

nontransplant therapies in preventing the fatal stage of the 

disease, statistical analyses were performed both with and 

without the transplanted cases. The suffixes LTi and LTe 




were added to all numbers, percentages, and probabilities 

listed or calculated including or excluding the LT cases, 

respectively. For each observation (line of the general 

table) with LT . 0, the number of treated patients, 

survivors, and deceased persons were corrected as follows: 

(i) for mortality rate excluding the transplant cases 

(MRLTe), the LT cases were removed from the data set, 

i.e., both treated patient and survivor numbers were 

decreased by the number of transplants, (ii) for mortality 

rate including the transplant cases (MRLTi), each LT 

patient was considered as a deceased person; only survivor 

numbers were decreased by the number of transplants. 

Complementary statistical analyses were carried out 

for 2062 LTi patients (2108 victims minus 46 

nonanalyzed-treatment cases) and 2031 LTe cases 

(2062 victims minus 31 LT cases); one LT case was in 

an unanalyzed mode of care. 

The global performance evaluation of each therapeutic 

mode was achieved by a statistical comparison of 

the number of survivors and nonsurvivors using a Chisquare 

calculation from the two rows (survivors, 

fatalities) and six columns (six tables) contingency 

table. The effect of each mode of care was studied by 

comparison of survivor and dead numbers in the 2 £ 2 

tables constituted from the general table. 

The Chi-square test applied to the general frequency 

tables rejected the hypothesis that outcome and treatment 

were independent; the distribution of survivors and 

deceased persons was statistically different for Tables 

1–6, both including and excluding the LT patients. When 

the p-value was #0.05, the null hypothesis was rejected 

at the 95% confidence level. The Yates’ correction was 

applied when the number of survivors or deceased 

patients was #5, and the Fischer’s exact test was 

calculated in the case of contingency table 2 £ 2 with 

less than 100 observations. The statistical analysis was 

carried out using STATGRAPHICS w PLUS software 

version 3.3 (Manugistics, Inc., Rockville, MD, USA). 

DESCRIPTION OF TREATMENTS 

The management of amatoxin poisoning involves four 

main categories of therapy: preliminary medical care, 

supportive measures, specific treatments, and LT. Since 

there is a relative consensus of opinion about 

the preliminary medical care and supportive 

measures, [14,18 – 20,23,223 – 228] only their major features 

are described. The specific treatments consisting of 

detoxication procedures, chemotherapies, and LT are 

described below in detail.

722 

Table 4 

Amatoxin Poisoning Cases Treated as Bi- and Tri-chemotherapy with Benzylpenicillin, with/without Detoxication Procedures and with/without Liver Transplant 


Detoxication 

ECP HD–HP/PL LT Surv. References 

Urin. 

FD 

Date/Country T/E Cases Mushroom Drugs Oral 

C/GA 



1977–1994 Germany 9/12 A.ph, a.sp ATB, silybin 0/9 9 9–9/0 0 8 [133] 

1977–1994 Germany 3/12 A.ph ATB, silybin 0/3 3 3–3/0 3 3 [133] 

1988 Turkey 2/27; 1 child L.cas, L.hel ATB, steroid 2/0 0 1–0/0 0 0 [82] 

1988 Turkey 1/3; child A.ph ATB, steroid 1/0 0 1–0/0 0 1 [134] 

1995 Turkey 3/3; 1 child A.ph, amat ATB, steroid 3/0 3 2–3/0 0 3 [135] 

1988 France 1/1 A.ph ATS, steroid 1/0 0 0–0/0 1 1 [136] 

1980 France 1/1 A.ph ATS, Vit.C 0/0 0 0–0/0 0 1 [137] 

1984 France 1/29 A.ph ATS, Vit.C 1/0 0 0–0/0 0 1 [138] 

1992 New Jersey 3/3 A.ph Cimetid 3/0 0 1–2/0 0 3 [139] 

1992–1993 New York 2/2 a.sp, amat Cimetid 2/0 0 0–0/0 0 1 [140] 


1999 Pennsylvania 5/6 A.ph, a.sp Cimetid 5/0 0 0–0/0 0 5 [124] 

1996–1997 California 1/10 a.sp Cimetid, 1/0 0 0–0/0 0 1 [109] 

NAC 

2000 Missouri 2/2 A.ph, amat Cimetid, 2/0 0 2–2/0 0 2 [141] 

NAC 

2000 Turkey 1/1; child a.sp Cimetid, 1/0 0 0–0/1 0 1 [142] 

Vit.C 

1986–1992 Italy 73/73; (child.) A.ph, amat NAC a 

73/0 73 0–0/0 0 67 [143–145] 

1996 France 1/1 L.bi, amat NAC 0/0 0 0–0/0 0 1 [146] 

1996–1997 California 6/10 1A.ph, 5 a.sp NAC 6/0 0 0–0/0 0 6 [109] 

1996–1998 Italy 11/11 A.ph, amat NAC 11/0 0 11–0/0 1 11 [116] 

1997 California 1/4 A.ph NAC 1/0 0 0–0/0 0 0 [90] 

1990 Italy 1/1; child a.sp, amat NAC, steroid 0/0 1 0–0/0 0 1 [147] 

1994 France 5/29 A.ph NAC, Vit.C 5/0 0 0–0/0 0 5 [138] 

1979–1988 France 29/29; (child.) A.ph, amat Silybin 0/0 0 (HD)–0/0 0 26 [148] 

1980–1986 Europe 159/252 A.ph, a.sp Silybin 0/0 (FD) (HD–HP)/0 0 156 [127,128] 

1985–1994 Sweden 22/41 A.ph, A.vi, a.sp, Silybin 22/0 0 22–22/0 0 22 [149] 

amat 

1988 California/Oregon 5/5 A.ph Silybin 0/0 5 0–0/0 4 5 [150,151] 

1988 Finland 4/4 A.vi Silybin 0/0 1 0–3/0 0 4 [152] 

1988 Norway 2/2 A.vi, amat Silybin 2/0 2 0–0/0 0 2 [153] 

1988–1994 Denmark 8/8 A.ph, A.vi Silybin 5/8 0 0–3/1 1 6 [154] 

1989 Italy 1/2 a.sp, amat Silybin 1/0 1 0–0/0 0 1 [83] 

1992 Germany 1/1 A.ph Silybin 1/1 0 0–0/1 0 1 [155]

1992 Germany 4/4; 1 child A.ph, amat Silybin 4/0 0 0–4/0 1 4 [156] 

1993 Czech 1/1; child A.ph Silybin 0/0 0 0–0/0 0 1 [157] 

1993 Germany 128/154 a.sp Silybin 0/0 0 0–0/0 0 113 [130] 

1993 Switzerland 5/5 A.ph, amat Silybin 5/0 0 0–0/0 0 5 [158] 

1994 The Netherlands 2/2 A.ph Silybin 2/0 0 0–0/0 0 2 [159] 

1994 Slovak Republic 1/1; pregnant A.ph Silybin 0/0 0 1–1/0 0 1 [160] 

1996 Italy 3/4 A.ph Silybin 3/0 0 0–0/0 0 3 [161] 




2001 Portugal 4/4; 1 child A.ph, a.sp Silybin 3/2 0 0–0/2 2 4 [162] 

1981–1983 Germany 6/13 A.ph, amat Silybin, 

0/0 0 0–6/0 0 6 [163] 

steroid 

1983 Germany 3/3 A.ph Silybin, 

0/0 0 0–0/0 0 3 [164] 

steroid 

1986 Denmark 11/11 A.ph, amat Silybin, 0/11 11 0–0/0 0 10 [165] 

steroid 

1994 Germany 2/2 A.ph Silybin, 

2/0 2 0–0/0 0 2 [166] 

steroid 

1980–1986 Europe 62/252 A.ph, a.sp Silybin, 

0/0 (FD) (HD–HP)/0 0 62 [127,128] 

Thioc.a 

1982–1986 Spain 2/85 a.sp, amat Silybin, 

2/2 2 0–2/0 0 2 [43,50] 

Thioc.a 

1986 Germany 1/1 A.ph, amat Silybin, 

1/0 1 0–1/0 0 1 [167] 

Thioc.a 

1991 Belgium 1/1 A.ph, amat Silybin, Vit.C 0/0 0 1–0/0 0 1 [168] 

1992 France 1/4; 1 child L.hel Silybin, Vit.C 1/0 0 0–0/0 0 1 [169] 

1993 France 1/29 a.sp Silybin, Vit.C 1/0 0 0–0/0 0 1 [138] 

1983–1987 Poland 5/90 A.ph, a.sp, amat Steroid 5/0 5 (HD)–0/0 0 4 [170–172] 

1984–1985 Poland 8/30 A.ph, a.sp Steroid 0/8 0 0–8/0 0 7 [173] 

1984–1985 Poland 22/30 A.ph, a.sp Steroid 0/22 0 0–0/0 0 16 [173] 

1988 Slovenia 10/10; 1 child A.ph, amat Steroid 10/0 0 0–0/10 0 9 [174] 

1988 Turkey 2/3; child. A.ph Steroid 1/0 0 1–0/0 0 2 [134] 

1988 Turkey 1/27 L.cas, L.hel Steroid 1/0 0 0–0/0 0 1 [82] 

1988–1989 Poland 47/90 A.ph, a.sp Steroid 47/47 47 0–0/27 0 42 [170,175] 

1979–1981 Italy 64/64 a.sp Steroid, 64/0 0 0–0/0 0 58 [176] 

Thioc.a 

1981 Italy 44/44; 4 child. A.ph, amat Steroid, 44/0 0 0–0/0 0 40 [177] 

Thioc.a 

1981–1983 Germany 1/13 A.ph, amat Steroid, 

0/0 0 0–0/0 0 1 [163] 

Thioc.a 

1990 Wisconsin 2/2 A.vi Steroid, 

1/1 2 0–2/0 0 2 [178] 

Thioc.a 

1984 France 2/29 A.ph Steroid, Vit.C 0/0 0 0–0/0 0 2 [138] 

(continued)

724 

Table 4. Continued 


Detoxication 



Urin. 

FD ECP HD–HP/PL LT Surv. References 

Oral 

C/GA 

Date/Country T/E Cases Mushroom Drugs 

1991–1998 Bulgaria 25/25 A.ph, a.sp Steroid, Vit.E 25/0 25 (HD–HP)/(PL) 0 15 [179] 

1977–1992 Slovak 58/58 A.ph Thioc.a 0/0 44 17–58/12 0 38 [180] 

Republic 

1979–1985 Sweden 19/41 A.ph, A.vi, a.sp Thioc.a 19/0 0 19–19/0 0 19 [149] 

1982–1984 Italy 2/6; child. A.ph, a.sp, amat Thioc.a 2/0 0 2–0/2 0 0 [181] 

1982–1986 Spain 59/85; (child.) 27 A.ph, 24 a.sp, 7 Thioc.a 18/15 28 0–4/2PL 3 EXE 0 56 [43,50,182– 

L.bi, 1 L.f 

184] 

1985 Italy 53/53; 6 child. A.ph, amat Thioc.a 53/53 (FD) (HD)–0/(PL) 0 47 [185] 

1986–1988 Spain 2/4 A.ph, amat Thioc.a 2/0 2 0–0/0 0 0 [182,183] 

1987 Italy 2/2 A.ph, amat Thioc.a 0/0 0 0–0/2 0 2 [186] 

1988 Spain 1/1 A.ph Thioc.a 0/0 0 0–1/0 0 1 [187] 

1989 Spain 10/10 3 L.bi, 7 L.hel, Thioc.a 10/0 0 0–10/0 0 8 [188] 

amat 

1990 Spain 1/1 A.ph Thioc.a 0/0 0 1–0/0 0 1 [189] 

b 

1982 Belgium 4/4; 1 child A.ph, amat Thioc.a, 

0/0 

0–0/0 0 3 [190] 

Vit.C 

1990–1994 France 11/29 5 A.ph, 6 a.sp Vit.C 4/0 0 1–0/0 0 10 [138] 

1992 France 3/4 L.hel Vit.C 1/0 0 0–0/0 0 3 [169] 


ECP ¼ extra-corporeal detoxication including HD ¼ hemodialysis, HP ¼ hemoperfusion, and PL ¼ plasmapheresis (or EXE ¼ exsanguino transfusion); LT ¼ liver transplant; 

Surv. ¼ survivors; amat ¼ amatoxins in biological fluids; undefined cases are reported in brackets; ATB ¼ antibiotic agent; ATS ¼ antiseptic agent (nifuroxazide); Cimetid ¼ cimetidine; 

NAC ¼ N-acetylcysteine; Thioc.a ¼ thioctic acid; Vit.C ¼ vitamin C; Vit.E ¼ vitamin E; a.sp ¼ amatoxin-containing species; A.ph ¼ Amanita phalloides; A.vi ¼ A. virosa; L.bi ¼ Lepiota 

brunneoincarnata; L.cas ¼ L. castanea; L.f. ¼ L. fulvella; L. hel ¼ L. helveola. 

a 

Neomycin instead of benzylpenicillin. 

b Spironolactone. 

Enjalbert et al.




Table 5 

Amatoxin Poisoning Cases Treated as Bi- and Tri-chemotherapy without Benzylpenicillin, with/without Detoxication Procedures and with/without Liver Transplant 


Detoxication 


1996 France 1/1; pregnant A.ph 2 ATB, NAC 1/0 0 0–0/0 0 1 [191,192] 

1983 California 1/1; child A.o 2 ATB, steroid 1/0 0 0–0/1 1 1 [193] 

1981 France 3/3 A.ph ATB, ATS, Vit.C a 

0/0 0 0–0/0 0 3 [194] 

1986 France 5/5; (child.) L.blil ATB, ATS, Vit.C a 

0/0 0 0–0/0 0 4 [195] 

1988 Turkey 3/27 L.cas, L.hel ATB, Thioc.a, Vit.C 3/0 0 3–0/0 0 1 [82] 

1989 France 6/6 A.ph, amat Ceftazid, silybin 6/0 0 0–0/0 0 6 [196] 

1990 France 5/5 A.ph, amat Ceftazid, silybin 5/0 0 0–0/0 0 5 [197] 

1994 France 1/1 L.blil Ceftazid, silybin 0/0 0 0–0/0 1 1 [198] 

1980–1986 Europe 6/252 A.ph, a.sp Silybin, Thioc.a 0/0 (FD) (HD–HP)/0 0 5 [127,128] 

1982–1984 Italy 4/6; child. A.ph, a.sp, amat Steroid, Thioc.a, Vit.C 4/4 0 0–0/4 0 4 [181] 



biological fluids; undefined cases are reported in brackets; ATB ¼ antibiotic agent; ATS ¼ antiseptic agent (nifuroxazide); Ceftazid ¼ ceftazidime; NAC ¼ N-acetylcysteine; 

Thioc.a ¼ thioctic acid; Vit.C ¼ vitamin C; a.sp ¼ amatoxin-containing species; A.o ¼ Amanita ocreata; A.ph ¼ A. phalloides; L.blil ¼ Lepiota brunneolilacea; L.cas ¼ L. castanea; 

L.hel ¼ L. helveola. 

a 

Bastien protocol.

726 

Table 6 

Amatoxin Poisoning Cases Treated as Poly-chemotherapy with/without Benzylpenicillin, with/without Detoxication Procedures and with/without Liver Transplant 


Detoxication 




1992 Michigan 1/1 a.sp 3 ATB, B.pen 0/0 0 0–0/0 1 1 [199] 

1996 Italy 1/4 A.ph 2 ATB, B.pen, Silyb 1/0 0 0–0/0 0 1 [161] 

1983 New York 1/1 L.jos, amat 3 ATB, Ster 0/0 0 0–1/0 0 0 [200] 

1984–1993 Germany 21/21; (child.) A.ph, amat ATB, B.pen, Silyb, Ster, 10/0 0 0–0/21 0 20 [201] 

TA 

1988 Turkey 2/27 L.cas, L.hel ATB, B.pen, Ster, TA 2/0 0 0–0/0 0 2 [82] 

1988 Turkey 1/27 L.cas, L.hel ATB, B.pen, Ster, TA, 1/0 0 0–0/0 0 1 [82] 

Vit.C 

1988 Turkey 4/27 L.cas, L.hel ATB, B.pen, Ster, Vit.C 4/0 0 0–0/0 0 2 [82] 

1984 France 4/29 A.ph ATS, B.pen, Silyb, Vit.C 0/0 0 0–0/0 0 4 [138] 

1988 France 2/29 A.ph ATS, B.pen, Ster, Vit.C 0/0 0 0–0/0 0 2 [138] 

1990 France 2/29 A.ph ATS, Silyb, Ster, Vit.C 0/0 0 0–0/0 0 1 [138] 

1988 Denmark 4/4 1 A.ph, 1 A.vi, B.pen, Cimet, Silyb, Ster 4/0 4 0–4/0 0 3 [202] 

2 a.sp 

1993 France 1/29 A.ph B.pen, NAC, Silyb, Vit.C 0/0 0 0–0/0 0 0 [138] 

1981–1983 Germany 6/13 A.ph, amat B.pen, Silyb, Ster, TA 0/0 0 0–5/0 0 5 [163] 

1991 Hungary 4/4; 1 pregnant A.ph, A.ve B.pen, Silyb, Ster, TA 4/0 4 0–0/0 0 3 [203] 

1993 Hungary 8/8; (child.) A.ph B.pen, Silyb, Ster, TA 0/0 0 0–6/1 0 7 [204] 

1983–1987 Poland 57/90 A.ph, a.sp, amat B.pen, Ster, Insul, Gluc 57/0 57 (HD)–0/0 0 47 [170–172] 

1988–1989 Poland 2/90 A.ph, a.sp, B.pen, Ster, Insul, Gluc 2/2 2 0–0/1 0 2 [170,175] 

1983–1987 Poland 28/90 A.ph, a.sp, amat B.pen, Ster, Insul, hGH 28/28 28 0–0/11 0 25 [170–172] 

1988–1989 Poland 41/90 A.ph, a.sp B.pen, Ster, Insul, hGH 41/41 41 0–0/29 0 33 [170,175] 



biological fluids; ATB ¼ antibiotic agent; ATS ¼ antiseptic agent (nifuroxazide); B.pen ¼ benzylpenicillin; Cimet ¼ cimetidine; Insul, Gluc ¼ insulin and glucagon; Insul, hGH ¼ insulin 

and human growth hormone; NAC ¼ N-acetylcysteine; Silyb ¼ silybin; Ster ¼ steroid; TA ¼ thioctic acid; Vit.C ¼ vitamin C; a.sp ¼ amatoxin-containing species; A.ph ¼ Amanita 

phalloides; A.ve ¼ A. verna; A.vi ¼ A. virosa; L.cas ¼ Lepiota castanea; L. hel ¼ L. helveola; L. jos ¼ L. josserandii; undefined cases are reported in brackets. 

Enjalbert et al.

Preliminary Medical Care 

Preliminary medical care consists of gastrointestinal 

decontamination procedures if appropriate, to make an 

attempt at obtaining baseline values of key biological 

parameters for diagnostic monitoring. When a patient 

develops a gastroenteritis 6–24 hours after mushroom 

ingestion, all asymptomatic and symptomatic persons 

who consumed the same meal should be immediately 

evaluated and treated as appropriate to prevent toxin 

absorption. Because of the long asymptomatic latency, 

the clinical utility of most gastrointestinal decontamination 

procedures seems limited. Although effective in 

inducing emesis, there is no evidence from clinical 

studies that ipecac syrup improves the outcome of 

poisoned individuals; data to support or exclude its 

administration are insufficient. [229] Gastric lavage should 

be considered only when it could be performed within 

60 minutes after ingestion of a life-threatening amount of 

toxin. [230] It is contraindicated if the patient has loss 

of airway protective reflexes or a decreased level of 

consciousness without endotracheal intubation. [230,231] 

There is no conclusive evidence for the use of whole 

bowel irrigation (WBI), which appears to decrease the 

binding capacity of the activated charcoal. [232] Some 

authors [13,14,22,23,233] advocate the administration of 

activated charcoal alone or with cathartics whereas 

others find no data supporting a cathartic in combination 

with activated charcoal. [234] 

The regional poison center can provide appropriate 

decontamination information and also suggest and track 

mycological, clinical, and biological data for each 

amatoxin victim. [223,231] The identification by a mycologist 

of any remaining mushrooms can be a key to 

diagnosis. The time lag between mushroom ingestion 

and hospital admission is an essential information. 

Biological parameters including blood sugar, serum 

transaminases (aspartate aminotransferase, ASAT; alanine 

aminotransferase, ALAT), lactate dehydrogenase 

(LDH), serum bilirubin, urea, and coagulation studies 

[prothrombin time (PT)] are proposed as indicators of 

hepatotoxicity. [18,19] Ryzko et al. [235] and Parra et al. [236] 

noted that hypocalcemia and alkaline phosphatase 

isoenzyme (ALP) are also indicators of amatoxin 

poisoning. Horn et al. [124] recommended concurrent 

measurement of serum markers of hepatocellular 

necrosis combined with markers of hepatocellular 

regeneration (g-glutamyl transferase and a-fetoprotein). 

Analysis of diarrhea fluids has been recommended 

since high levels of amatoxins are eliminated in feces. 

Amatoxins may also be assayed in urine and serum by 




radio-immunoassay, [237,238] high-performance liquid 

chromatography with UV detection method as reviewed 

by Dorizzi et al., [239] electrochemical detection, [240] and 

capillary electrophoresis. [241] Thin layer chromatography 

using a color index of amatoxins by Schiff’s test is 

reported by Russian authors. [242] Unfortunately, the 

amatoxin concentrations in biological samples do not 

correlate with the severity of poisoning and do not 

indicate intra-hepatic toxin accumulation. High individual 

differences in urinary amatoxin concentrations may 

only be of qualitative value. [243] 

Supportive Measures 

Supportive measures for the management of gastroenteritis 

and hepatotoxicity are so frequently used that an 

analysis of their utility was not attempted with this data. 

In the gastrointestinal phase, diarrhea and emesis can 

produce hypovolemic shock requiring intensive intravenous 

fluid resuscitation. Electrolyte abnormalities, 

metabolic acidosis, hypoglycemia, impaired coagulation 

due to decreased hepatic synthesis of Factors II, V, VII, 

and X are corrected. A normal or slightly high urine 

output is maintained during the first 48 hours to avoid 

acute renal failure. Parenteral nutrition with protein 

intake restriction is instituted. 

Specific recommendations for supportive treatment of 

hepatoxicity include: (i) correction of coagulation 

disorders by parenteral vitamin K (10 mg daily for 

three consecutive days), fresh frozen plasma and 

antithrombin III, (ii) oral lactulose and neomycin to 

prevent encephalopathy, [244] and (iii) mannitol to lower 

intracranial pressure and avoid cerebral edema. [245] 

Ninety-one of the 2108 patients reported since 1980, 

including six LT victims, were given supportive 

measures alone (Table 1). A total of 2017 of 2108 

victims were treated with supportive measures combined 

with specific treatments as detoxication procedures alone 

(Table 2) and various protocols of chemotherapy with or 

without detoxication procedures (Tables 3–6). 

Detoxication Procedures 

Detoxication involves two different approaches: the 

reduction of absorption and enhancement of 

excretion. [246] 

Oral Detoxication 

Theoretically activated charcoal should bind amatoxins 

excreted via the bile into the duodenum and upper 

jejunum, although there is no evidence that its use

728 

improves clinical outcome if it is used more than 1 hour 

after ingestion. [247] Toxicokinetic studies in the dog 

suggested amatoxin absorption or reabsorption from the 

intestine. [248] Given the enterohepatic circulation of 

amatoxins, administration of activated charcoal as 

multiple doses could reduce amatoxin absorption if in 

contact with toxin present in the gastrointestinal tract. 

Serial charcoal dosing either as a continuous nasogastric 

drip or pulse dosing with 20–40 g every 3–4 hours (for 

24 hours or more) has been advocated by most authors as 

a relatively noninvasive enterohepatic and enteric 

dialysis technique. [42,74,233,249 – 251] However, clinical 

data are insufficient to support or exclude this oral 

detoxication method. [247] 

Gastroduodenal aspiration (GA) from the upper 

portion of the small intestine through a nasogastric tube 

has been recommended as a sole technique or combined 

with activated charcoal to remove bile fluids and 

interrupt enterohepatic circulation [252] but the actual 

benefit of these procedures is not documented. 

Amatoxins are present in the gastroduodenal fluids 

until 60 hour after mushroom ingestion. [253] Long term 

intubation may lead to side effects of bleeding and 

pancreatitis and is not always recommended. [14] 

Urinary Detoxication 

Toxicokinetic reports of human mushroom poisoning 

have shown that diuresis substantially enhances the 

amatoxin elimination rate. Large amounts of amatoxins 

(60–80%) are filtered through the glomeruli. [254] Urinary 

elimination of amatoxins has been detected within the 

first 8 hours and for 3–4 days after mushroom 

ingestion. [167] Amatoxin concentrations in the urine are 

from 100 to 150 times higher than those of serum and can 

be quantified even when no serum circulating amatoxins 

are detectable. [50,51,255 – 257] Maintenance of early and 

adequate urine output is theoretically important even 

though there is no re-absorption in the proximal tubules 

or tubular secretion; “forced diuresis (FD)” with fluids 

plus a loop diuretic cannot increase amatoxin elimination. 

[14,248] According to Jaeger et al., [257] there is no 

proof that FD decreases the amount of amatoxins bound 

to the hepatocytes or is more efficient than the 

maintenance of an adequate diuresis (from 100 to 

200 mL/h). Furthermore, FD is difficult to maintain in a 

patient with a severe dehydration. 

Extra-corporeal Purification Procedures 

Amatoxins are detected in the serum from 24 to 

48 hours after mushroom ingestion but at very low 




[253,256 – 258] 

concentrations when compared to the urine. 

Extra-corporeal elimination includes hemodialysis (HD), 

hemoperfusion (HP), plasmapheresis (PL), and related 

methods. HP and HD are theoretically helpful since the 

amatoxins are easily dialyzable due to their free 

circulation in the serum and their small molecular 

weight (about 900 Da); amatoxins also possess a high 

affinity for charcoal and polymers used for HP cartridges 

and dialyzer membranes. [249] HD initiated as sole 

treatment has been reported to be ineffective in the 

management of amatoxin syndrome [82,97] but should be 

instituted if renal failure occurs. [231] Given the low serum 

amatoxin concentration, the utility of toxin removal by 

extra-corporeal purification procedures is questionable. 

Extra-corporeal purification procedures such as HD, HP, 

and PL, and related methods such as continuous 

venovenous hemofiltration and exsanguino-transfusion, 

are often used in a combined mode; it is difficult to assess 

the efficacy of any single treatment. 

HP has been applied to amatoxin-intoxicated patients 

since 1978 with a possibly favorable effect. [259 – 261] It 

has been carried out within the first 36 or 48 hours after 

ingestion [246,260,262] but is proposed as most effective if 

applied prior to 24 hours. [231] The survival rate of 

poisoned patients is claimed to depend on the time of 

beginning HP. [14,140,180] Polish and Turkish retrospective 

studies have reported increased survival for amatoxinpoisoned 

patients treated with HP. [107,173] 

Thrombocytopenia, a major side effect of HP that 

increases the risk of bleeding, [123,149] diminishes when a 

platelet protective agent such as prostacyclin is 

administered. [123] Other complications of HP such as 

hypotension due to volume loss, hypoglycemia, and 

hypocalcemia must be monitored and corrected. [262] 

Controversy centers on whether the blood level of 

amatoxins is high enough to justify this procedure. 

[249,258] HP performed within 12–14 hours after 

ingestion of amatoxin-containing mushrooms eliminated 

less than 4% of the ingested toxin dose. [225] Although the 

benefit of HP to remove amatoxins in the early stages of 

intoxication was debatable, [263] it may help support the 

patient during hepatic failure. [155] HP eliminates 

neurotropic and neurotoxic amino acids and mercaptans; 

it has been reported to ameliorate the hepatic 

encephalopathy in 75% of amatoxin poisoned 

patients. [264,265] 

The HP sorbent most frequently used is activated 

charcoal. In the United States, the only available HP 

sorbent is activated charcoal-coated polymer membranes. 

[262] The efficacy of ion-exchange resin (Amberlite 

XAD-4) has been experimentally demonstrated. [266]

Czechoslovakian investigations of the in vitro absorption 

of a- and b-Ama standards, using charcoal as well as 

XAD-2 and XAD-4 resin types, found Amberlite XAD-2 

synthetic resin the most effective and activated charcoal 

the least. [267,268] Positive results from in vitro experiments 

with Amberlite XAD-2 resin are said to justify 

further trials of this material in the detoxication 

procedures of clinical amatoxin poisonings. [269] 

HP is often combined with HD; some reports claim it 

is helpful. [14,159,249] American reports on the clearance of 

amatoxins in a series of blood samples taken from 

poisoned patients before and after treatment as well as in 

the HD/HP circuits demonstrate no utility. [141] Italian 

authors have recently reported the combination of 

charcoal plasmaperfusion and continuous venovenous 

hemofiltration (Table 2) to eliminate both low and high 

molecular weight toxins. This new method of toxin 

removal might improve the liver function of amatoxin 

intoxicated patients. [111] 

The first uses of PL in mushroom poisoning in 

general [270] and Amanita poisoning in particular, [271] 

were reported in the late 1970s. Several authors [98,272] 

and most recently Jander et al. [273] reviewed advantages 

and problems relevant to PL for amatoxin-intoxicated 

patients. 

PL performed as a single detoxication procedure [98] 

or in combination with other extra-corporeal purification 

methods such as HD/charcoal HP [97] or Amberlite XAD- 

2HP [215] has been reported to decrease mortality. PL 

plus chemotherapy are also said to improve survival 

as well as the general condition of poisoned patients 

by stabilizing biliary acid and bilirubin levels. [131,174] In a 

large study, mortality was 7.4% when PL plus chemotherapy 

was used for 68 of 180 patients and 

19.6% when the PL was not used. [175] German authors 

also reported that early combined treatment 

with PL plus chemotherapy was beneficial. [273] According 

to 18-year Italian experience, plasma-exchange 

therapy associated with general intensive care 

may improve the health of amatoxin poisoned 

patients who retain sufficient capacity for liver 

regeneration. [100] 

Patterns and Frequency of Detoxication 

Procedures 

Of the 2017 amatoxin-poisoned individuals administered 

specific treatments, 385 (19.1%, Table 2) underwent 

only detoxication procedures (Detox-group) while 

1632 (80.9%, Tables 3–6) received chemotherapy 




(Chem-group) either alone or combined with detoxication 

procedures. 

Activated charcoal (C) was given to 7.5% (29/385) 

Detox-group patients and to 35.7% (583/1632) 

Chem-group patients. GA was performed in 

3.6% (59/1632) Chem-group patients. Combined 

C þ GA was reported for 2 of 385 Detox-group patients 

and 223 of 1632 (13.7%) Chem-group patients. 

FD was undertaken in 49.4% (190/385) Detox-group 

patients and at least 33% of Chem-group patients. 

HD was reported for 30.6% (118/385) Detox-group 

and at least 7.1% of the 1632 Chem-group patients. HP 

was reported for 57.4% (221/385) Detox-group and at 

least 11.4% of the Chem-group patients. PL was cited for 

5.2% (20/385) Detox-group and at least 9.6% of the 

Chem-group patients. 

The inadequate reporting of HD and extra-corporeal 

procedures in the sources comprised in Tables 3–6 

among the patients who also received chemotherapy 

necessitated the pooling of patients receiving the same 

chemotherapy with and without detoxication procedures. 

Chemotherapy with Specific Agents 

No specific amatoxin antidote is available, but 

therapeutic agents such as b-lactam antibiotics, silymarin 

complex, thioctic acid, antioxidant drugs and other 

drugs are used in the clinical management of amatoxin 

poisoning. In vitro experiments and animal model 

investigations have been summarized along with the 

purported advantages and disadvantages of their clinical 

use. In this survey, the 1632 patients in the Chem-group 

received drugs as mono-chemotherapy (Table 3), bichemotherapy 

with or without benzylpenicillin (part of 

Table 4 and part of Table 5, respectively), trichemotherapy 

with or without benzylpenicillin (part of 

Table 4 and part of Table 5, respectively) or polychemotherapy 

(.3 drugs) with or without benzylpenicillin 

(Table 6). Patients in the Chem-group may have 

also received detoxication procedures. 

b-Lactam Antibiotics 

Benzylpenicillin (Penicillin G) and ceftazidime are blactam 

antibiotics thought to be hepatoprotective in 

amatoxin poisoning. Benzylpenicillin was first used to 

protect mice and rats against lethal doses of either A. 

phalloides extracts or a-Ama. [274,275] In dogs orally 

poisoned with a sub-lethal dose of A. phalloides 

preparation, intravenous benzylpenicillin injection

730 

prevented both the rise of the liver enzymes and the fall 

of clotting factors in the blood. [276] 

Benzylpenicillin perfusions of isolated rat liver 

showed a strong inhibition of a-Ama toxicity. [277] 

Although most b-lactam antibiotics utilize a common 

carrier system for uptake into isolated hepatocytes, [278] 

kinetic studies of a-Ama absorption in hepatocytes 

proved that benzylpenicillin does not inhibit the 

membrane transport systems used by the toxin. An 

intracellular mechanism rather than interference with 

amanitin uptake appears responsible for the purported 

hepatoprotective effect. [279] 

Several theories have been advanced to explain the 

antitoxic action of benzylpenicillin. Floersheim’s 

hypothesis [280] 

that the drug could displace a-Ama 

from its binding site on serum protein is challenged by 

evidence that the toxic cyclopeptide does not bind to 

serum albumin. [266,281] Another hypothesis suggested 

that benzylpenicillin reduced or eliminated the GABAproducing 

intestinal flora involved in hepatic encephalopathy. 

[250,280] Although GABA appeared to be involved 

in experimental hepatic encephalopathy, the inhibitory 

neurotransmitter does not seem to play a role in human 

encephalopathy. [282] 

Other reports presented evidence of an anti-proliferative 

effect of b-lactam antibiotics on cultured 

eukaryotic cells including human sources and in vitro 

DNA replication systems. The intracellular target of blactams 

appears to be the replicative enzyme polymerase 

I. [283,284] Since the amatoxins, particularly a-Ama, are 

selective blockers of DNA-dependent RNA polymerase 

II, it is possible that the b-lactam antibiotics protect via 

their effects on eukaryotic DNA replication. [285] 

Although there is no formal proof, in vitro experiments 

on chicken embryo hepatocytes and in vivo studies on 

mouse liver have shown that b-lactam antibiotics inhibit 

the toxic effect induced by a-Ama. [286] 

Unfortunately, benzylpenicillin commonly causes 

allergic drug reactions with an incidence of 

1–10%. [126,287 – 289] The large amount of sodium ions 

administered with this antibiotic agent to amatoxinpoisoned 

patients may disrupt electrolyte balance. [290,291] 

Severe granulocytopenia has also been observed with 

high doses of benzylpenicillin. [292 – 294] Degradation 

products formed in vitro are often the causative agents 

of such adverse reactions rather than parent antibiotic. 

Use of freshly prepared single doses of benzylpenicillin 

prevents the majority of side effects. [295] However, given 

the bone narrow toxicity of b-lactams, these antibiotics 

[189,285] could affect all the hematopoietic cell 

lines. Lastly, massive benzylpenicillin therapy may 



evoke neurotoxic symptoms in patients with nervous 

system disease and renal insufficiency as well as induce 

convulsions when cerebral edema is imminent. [14,296] 

Although the biological mechanism of b-lactam 

antibiotics in the treatment of amatoxin poisoning is still 

unclear and high-dose benzylpenicillin can induce 

adverse reactions, the literature seems to support clinical 

benefits. Moroni et al. [297] reported 100% recovery for 33 

patients treated 1 or 2 days after ingestion of Amanita 

mushrooms with high doses of IV benzylpenicillin plus 

thioctic acid and steroids. Statistical analysis of a clinical 

study of 205 patients from Austria, France, Italy, 

Switzerland, and The Netherlands from 1971 to 1980 

found benzylpenicillin at 300,000–1,000,000 U/kg/day 

IV to be significantly associated with survival. [250,298] 

The suggested doses for benzylpenicillin are 40,000,000 

and 1,000,000 U/day in adults and children, respectively. 

[265] Benzylpenicillin is not approved by the US 

Food and Drug Administration (FDA) for treatment of 

Amanita poisonings. 

In this 20-year survey, benzylpenicillin was the most 

frequently used drug in the management of amatoxin 

poisoning, either as mono-chemotherapy in 164 

cases (10.1%, Table 3) or combined with other drugs 

as bi-chemotherapy (797 cases, 48.8%, Table 4), trichemotherapy 

(263 cases, 16.1%, Table 4), and polychemotherapy 

(187 cases, 11.5%, Table 6). In total, 

86.5% of Chem-group patients (1411/1632) receiving 

chemotherapy were treated with benzylpenicillin. 

Ceftazidime, a third generation cephalosporin, is 

several times more effective than benzylpenicillin by 

DNA replication systems testing in vitro. [284,286] 

According to the Neftel protocol, [196] ceftazidime is 

administered as 4.5 g IV every 2 hours. Despite the high 

drug concentrations in plasma, no renal and neurological 

side effects were reported. [197] Ceftazidime was the 

second most used b-lactam but was always combined 

with silybin (12 cases, Table 5). 

Silymarin Complex 


Silymarin is a hepatoprotectant complex of natural 

substances isolated from seeds of Mediterranean milk 

thistle, Silybum marianum (L.) Gaertn. (Asteraceae ). [299] 

This flavonolignan group includes the three isomers 

silydianin, silychristin, and the major compound, 

silybin. [300,301] The beneficial effects of silymarin on 

death rate and survival time in intraperitoneal (IP) 

administered mice with a-Ama were reported by Hahn 

et al. [302] Silymarin efficacy depended on both the delay 

between intoxication and therapy, and the degree of liver

damage. [303] Silymarin markedly increased the survival 

of mice poisoned with IP A. phalloides extracts. [304] In 

dogs, which display poisoning resembling human 

intoxication, silymarin suppressed both the rise of liver 

enzymes and the fall of clotting factors, and silybin 

noticeably reduced the degree of bloody necrosis in 

animal livers after oral A. phalloides extract. [276,305] 

Histochemical studies on isolated rat hepatocytes 

have elucidated the mechanism of silymarin hepatoprotection. 

The flavonolignan complex bound tightly to liver 

plasma membrane acts as a membrane stabilizer [306,307] 

whereas flavonoid substances such as taxifolin, morin, 

and quercetin have no effect. [308] 

Silymarin hindered a-Ama penetration of the cell 

wall. [277,303,308] Silybin competed with a-Ama for the 

multi-specific bile salt transport systems of the 

hepatocyte membrane. [279] Histoenzyme analyses of 

liver from a-Ama poisoned mice revealed that factors 

disturbed by the toxin, including glucose-6-phosphatase, 

aminopeptidase, ATPase, glycogen, lipid, and nucleic 

acid, were restored by silybin. [309] 

Silymarin and silybin are also radical scavengers 

acting as chain-breaking antioxidants. [310 – 315] Silymarin 

complex, by preserving alkaline phosphatase activity, 

prevented changes in membrane phospholipid composition 

and inhibited the lipid peroxidation in both rat liver 

microsomes and isolated hepatocytes. 

[310 – 312,316 – 318] 

The action site of silymarin is the hepatocyte outer 

membrane where the drug maintains lipid composition 

and aids functional integrity. [316] 

Silybin in isolated rat Kupffer cells showed inhibition 

of the cyclooxygenase and 5-lipooxygenase pathway of 

arachidonic acid metabolism and the subsequent 

synthesis of the inflammation mediator leukotriene 

B4. [319] Silymarin also produced a high anti-inflammatory 

effect in vivo by inhibition of leukocyte migration 

into the inflamed site. [320] Silymarin exerted an 

antifibrotic activity and retarded collagen accumulation 

in early and advanced biliary fibrosis secondary to 

complete bile duct obliteration in rats. 

[321 – 323] 

Silybin favored the regenerative process of both liver 

and Kupffer cells of partially hepatectomized rats. [324] 

These results agree with the observation that silybin 

stimulates liver cell metabolism. [325] It increased the 

synthetic rate of ribosomal RNA not only in rat hepatocyte 

but also in the isolated hepatocyte nucleus, via 

activation of DNA-dependent RNA polymerase I. As a 

consequence of this stimulation, ribosome formation was 

accelerated and protein synthesis increased. Although 

protein and RNA syntheses are prerequisites for DNA 

synthesis, silybin had no effect on DNA formation in cell 




cultures and liver of normal rats whereas an effect could 

[326 – 

be observed in liver of partially hepatectomized rats, 

329] 

suggesting that silybin stimulates protein biosynthesis 

and regenerates damaged liver tissue. 

Levels of silymarin components are found to be low in 

plasma and urine after oral and IV silybin administered to 

rats and after oral silymarin to cholecystectomized 

patients. [330] The three isomers, silybin, silydianin, and 

silychristin (silymarin complex) were excreted mainly by 

the biliary route either free or as sulfate and glucuronide 

conjugates. [330,331] 75–90% of the administered dose of 

silybin is metabolized to glucuronide and sulfate 

conjugates, which are partly hydrolyzed and cycled 

enterohepatically. [315] Silybin elimination is estimated as 

20–40% over a 24-hour period with a maximum between 

2 and 9-hour post-administration. [332] Thus, silybin in the 

bile theoretically inhibits enteric absorption and interrupt 

enterohepatic circulation of the amatoxins. [249,333] 

Silybin administration within 60 hours after a toxic 

mushroom meal blocked the increased alanine amino 

transferase (ALAT) and restored other parameters of 

liver dysfunction. [315,334] 

After oral silymarin, collected bile contained high 

amounts of isosilybin (a silybin isomer) and very low 

levels of silydianin and silychristin. The low concentrations 

in plasma and bile of both silydianin and 

silychristin indicate a minor contribution of these 

compounds to the hepatoprotective effect of silymarin 

complex. [335] 

In order to increase silybin concentration in the bile, 

recent studies have combined silybin with phosphatidylcholine; 

this lipophilic complex is called silipide (IdB 

1016). Silybin concentrations in patient bile after silipide 

administration were several-fold higher than after oral 

silymarin. This suggests that such complexation 

increased the oral bio-availability of silybin. It is likely 

that drug passage through membranes of the gastrointestinal 

tract was facilitated, favoring hepatic delivery. 

[335,336] 

Advances in the knowledge of the hepatoprotective 

properties of silymarin complex have yielded convincing 

experimental evidence for the efficacy of silybin and 

justified its use in human amatoxin poisoning. However, 

according to Wellington and Jarvis, [315] the value of 

silymarin relates to the toxin dose and time lag before 

drug administration. In a clinical series of 205 cases, all 

patients who received silybin survived. [298] Reviewing 

the recovery of 18 cases of Amanita poisoning treated 

with silybin, Hruby et al. [290,291] concluded that the drug 

administered even up to 48 hour after toxic mushroom 

ingestion was effective in preventing severe liver

732 

damage. In a retrospective study of 175 cases with a 

mortality rate of 8.6%, [315] 131 patients were treated with 

silybin/benzylpenicillin combination (14 deaths) and 44 

patients received silybin alone (one death). However, the 

mean interval between mushroom ingestion and institution 

of silybin therapy as well as the severity of poisoning 

were not identical for the two therapeutic modes. 

Table 3 lists 74 amatoxin-poisoning cases (4.5% of 

1632) treated with silybin as mono-chemotherapy and 

Tables 4–6 list 550 cases (33.7% of 1632) treated with 

silybin in combination with other drugs. Some authors 

suggested the combination of silybin plus benzylpenicillin 

to be more beneficial than other combinations. 

[18,69,224,337] Faulstich and Zilker thought that 

both drugs act as competitive inhibitors of the amatoxintransporting 

system and should not be used in 

combination [14] but did not consider the disparate effects 

of benzylpenicillin and silybin on a-Ama uptake 

reported by Kröncke et al. [279] In our survey, 379, 102, 

and 49 of 1632 amatoxin intoxicated patients received 

silybin/benzylpenicillin as bi-chemotherapy (23.2%, 

Table 4), tri-chemotherapy (6.3%, Table 4), and polychemotherapy 

(3%, Table 6), respectively. 

The initial dose of silybin dihemisuccinate is 5 mg/kg 

by IV infusion over 1 hour followed by 20 mg/kg/day by 

continuous infusion for six days until transaminase levels 

have normalized. [315] In the United States, silymarin is 

available only as a food supplement; at this time there is 

no active Investigational New Drug (IND) application 

for any component of the silymarin complex in the U.S. 

FDA. [231,315,338] 

No serious side effects have been observed with 

silybin [225] but nausea, epigastric discomfort, arthralgia, 

headaches, pruritus, and urticaria have been reported. 

Due to a lack of adequate clinical investigations, silybin 

is not administered to children under 12 years of age, 

unless the benefits outweigh the risks. [315] Oral 

silymarin, Legalon w and b-cyclodextrin silybin have 

been recommended as an alternative to parenteral 

silybin. [133,339] 

Hepatoprotective activity of the Extractum Silybi 

fluidum (fluid extract) and “Silybochol” against rat liver 

damage caused by CCl 4 was recently shown. This 

preliminary finding suggests potential utility in clinical 

trials of the bio-active substances from S. marianum fruit 

powder, fluid extract, and fatty oil. [340] 

Thioctic Acid 

Mechanistic studies on thioctic acid (a-lipoic acid; 

1,2-dithiolane-3-pentanoic acid) suggest a rationale for 




potential benefit in amatoxin hepatotoxicity. Acting as a 

free radical scavenger, it might prevent lipid peroxidation 

of the cell membrane by dissociating the hydrogen 

ion on the sulfhydryl groups of dihydrothioctic acid, its 

main metabolite. [354] Due to the antioxidant activity of 

both oxidized and reduced forms, affecting in vitro 

cellular metabolic processes, thioctic acid is capable of 

regenerating directly vitamin C and indirectly vitamin E, 

as well as influencing the increase of intracellular 

glutathione content. [355,356] Thioctic acid has a therapeutic 

potential in the treatment of hepatic diseases 

induced by chemical agents in animal models as 

reviewed by Bustamante et al. [356] 

It was introduced for the treatment of amatoxin 

poisoning in the Czech Republic by Kubicka in 1969. [341] 

The successful use of a-lipoic acid was also reported 

from Italy [342,343] and then reviewed in the Eastern 

European literature. [344,345] In the United States, the first 

use of thioctic acid was described in 1972 in New Jersey 

for A. verna intoxication with apparently beneficial 

result. [346] The cause–effect relationship between 

thioctic acid administration and clinical improvement 

in amatoxin poisoning is not clearly established and 

opinion concerning efficacy is divergent. [347 – 351] Early 

enthusiasm in the United States waned as investigations 

of thioctic acid carried out in Amanita poisoned mice and 

dogs reported either a severe glucose imbalance [352] or 

ineffectiveness of the drug. [353] A controlled clinical trial 

was never conducted and there were too few patients 

enrolled in the IND study to support a claim of efficacy. 

This drug is unavailable for human use in the United 

States. Multiple authors discourage its clinical 

use. [74,352,357 – 359] According to Floersheim et al. [298] 

and Floersheim [360] the administration of thioctic acid is 

often associated with a fatal outcome and it should be 

removed from the therapeutic protocol. [231] Other 

authors support thioctic acid trials in amatoxin poisoning 

until its efficacy can be confirmed or refuted. [23,361,362] 

Given the experimental findings of hypoglycemia as a 

major side effect of thioctic acid, [348,352] the drug should 

beadministeredwithasustainedIVdripofglucose. [349,363] 

In clinical use, thioctic acid was combined with glucose 

in IV infusions at doses of (i) 300 mg/kg/day in four 

divided doses and then 600 mg/kg/day [73,361] and (ii) 

50–150 mg/kg/day. [364] Allergic skin reactions have 

been reported. [355] Because it is sensitive to light and 

heat, bottles and infusion lines containing the solution 

must be wrapped in aluminum foil. [231,347,349] 

In this 20-year case survey beginning in the 1980s, 

thioctic acid was used in 8 of 1632 amatoxin poisonings 

(0.5%, Table 3) as single chemotherapy and in 442 of

1632 (27.1%, Tables 4–6) in combined chemotherapy. 

Thioctic acid/benzylpenicillin was given as bi-chemotherapy 

(207 of 1632, 12.7%, Table 4), tri-chemotherapy 

(180 of 1632, 11%, Table 4), and poly-chemotherapy (42 

of 1632, 2.6%, Table 6). 

Antioxidant Drugs 

In recent years, authors have postulated that the 

oxidant effects of amatoxins could be counteracted by 

the use of antioxidants such as ascorbic acid, cimetidine, 

and NAC. [116] 

L-ascorbic acid (vitamin C) is widely distributed in the 

plant and animal kingdoms. Biochemistry, physiological 

properties, and clinical uses of this chemical agent have 

been extensively reviewed. [301,365] Vitamin C inhibits 

lipid peroxidation and is used as hepatocyte protector in 

damage due to acetaminophen and CCl4. [366] It was 

introduced in the emergency treatment of A. phalloides 

intoxication 20 years ago as part of a multi-drug regimen 

(plus nifuroxazide and dihydrostreptomycin) devised by 

Bastien. [194,367,368] The regimen was reviewed by 

Chabré [369] and is still used in French poison centers. [231] 

Our survey found use of vitamin C, usually in 

combination with benzylpenicillin, in 60 cases (3.7%, 

Tables 4–6). 

Cimetidine, a cytochrome P450 inhibitor, is an 

antioxidant agent with cytoprotective and antifibrinolytic 

effects. [301,370] Therapeutic use in the management of 

amatoxin poisoning is based on the clinical similarity of 

this intoxication to liver damage due to other toxins 

affecting cytochrome P450. Histological examination of 

livers from a-Ama poisoned mice revealed major 

mitochondrial changes while the hepatic mitochondria 

were preserved in a-Ama poisoned mice treated with 

cimetidine either prophylactically or within 6 hours. [371] 

A three-drug combination of cimetidine, benzylpenicillin, 

and ascorbic acid significantly improved enzymatic 

and histopathological changes and survival rate of a- 

Ama intoxicated mice. [372] Clinical cimetidine treatment 

was reported for only 21 amatoxin poisoned patients 

(1.3%, Tables 3, 4, and 6) at a dose of 300 mg IV 

administered every 8 hours and usually in association 

with benzylpenicillin. 

NAC acts as a glutathione precursor when natural 

stores are depleted and is also a scavenger of free radicals 

formed in paracetamol poisoning. [373,374] The similarity 

between the clinical toxicities of a-Ama and paracetamol 

suggested NAC inclusion in the management of 

amatoxin poisoning. [125,143 – 145] Japanese authors investigating 

mushroom toxicity in isolated rat hepatocytes 




showed that Amanita extracts (in particular A. virosa ) 

markedly decreased intracellular glutathione content. 

[375] However, the negative results observed with 

NAC treatment for amatoxin poisoned mice indicate that 

amatoxin metabolism is probably not identical to that of 

paracetamol and that glutathione may play little or no 

role in amatoxin hepatotoxicity. [376] Over the 20-year 

period, 89 of 1632 amatoxin cases (5.5%, Table 3) 

received chemotherapy with NAC alone and 103 of 1632 

(6.3%, Tables 4–6) received NAC combined with other 

drugs, usually benzylpenicillin. 

Miscellaneous Drugs and Prospective 


Other drugs such as antibiotics, antiseptic agents, 

hormones and steroids used in the management of 

amatoxin intoxicated patients are listed in Tables 3–6. 

To our knowledge, no experimental evidence is reported 

of any hepatoprotective effect of antibiotics such as 

aminoglycoside derivatives (gentamycin, neomycin, 

streptomycin), cyclopeptide derivatives (vancomycin), 

and macrolide derivatives (clindamycin). These agents 

are not considered in our retrospective analysis. The 

antiseptic agent nifuroxazide plus dihydrostreptomycin 

and vitamin C is part of Bastien’s regimen. [194,367,368] 

The role of hormones and steroids in the management of 

amatoxin syndrome is questionable. Other agents 

proposed for therapy include iridoid glycosides and 

immunotherapy and are discussed below. 

Insulin and human growth hormone (hGH) were 

reported to be effective in rat liver regeneration after 

Amanita poisoning. [377] Intravenous infusion of either 

insulin/glucagon or insulin/hGH, in combination with 

glucose, was administered to amatoxin poisoned children 

by clinicians in Poland in an attempt to stimulate liver 

cell metabolism. [172,175] A randomized clinical series of 

FHF cases showed no effect of insulin/glucagon on liver 

regeneration. [378] 

Experiments on a-Ama uptake into hepatocytes 

suggested that prednisolone might exert a protective 

effect by competition between the steroid and toxin for 

the transport systems and not by nonspecific effects upon 

the cell membrane. [279] Investigations of steroids in mice 

and dogs poisoned with either A. phalloides extract or a- 

Ama revealed a positive effect on recovery of mice but 

not on survival of dogs. [276,304] Since steroids have no 

efficacy in acute hepatic failure, the American and 

European Associations for the Study of the Liver 

excluded these drugs for this indication 25 years ago. [264] 

A 1979 double-blind randomized trial with acute hepatic

734 

failure cases treated by hydrocortisone confirmed that 

steroids improved neither hepatic function nor survival 

rate. [379] 

Although steroids were included as therapeutic agents 

for Amanita poisoning by Floersheim et al. in 1982, [298] 

he suggested removal of steroids from treatment 

protocols in 1985 because of lack of correlation with 

the outcome. [360] Despite this, in the cases published 

since 1980 steroids were reported in the treatment as 

mono-chemotherapy (8 of 1632, 0.5%, Table 3) and as 

bi-, tri-, and poly-chemotherapies with benzylpenicillin 

(443 of 1632, 27.1%, Tables 4 and 6), and without 

benzylpenicillin (0.5%, 8 of 1632, Tables 5 and 6). 

Iridoid glycosides such as aucubin and kutkin 

represent a group of monoterpene glycosides with a 

cyclopentane-(c)-pyran ring structure widely distributed 

in the plant kingdom. [380] Aucubin is a common iridoid 

glycoside isolated from Eucommia ulmoides Oliver 

(Magnoliaceae ), [381] Plantago asiatica L. (Plantaginaceae 

), [382] and Aucuba japonica Thunb. (Corna- 

ceae ). [383] 

Iridoid compounds have recently been 

successful in experimental amatoxin poisoning, and on 

the basis of the promising results, these drugs may merit 

clinical evaluation. Protective activities of aucubin 

against a-Ama have been reported in beagle dogs orally 

poisoned by A. virosa extract, and in mice I.P. administered 

with the toxin, even when the treatment was begun 

12 hours later. [380,382] According to these authors, the 

mechanism of hepatoprotection might be attenuation of 

the continuous depression of liver m-RNA biosynthesis 

caused by a-Ama. [382,384] This mechanism was not 

confirmed in rat studies, however, aucubin enhanced 

excretion of a-Ama suggesting that it or one of its 

hydrolyzed products may displace the toxin from binding 

sites. [385] Oral administration is ineffective; [380,384] and 

the influence of the route of administration on efficacy 

may merit elucidation. [386] As far as we know, no 

investigation of aucubin in humans has been conducted. 

Picrosides I–III and kutkoside, known collectively as 

kutkin, were isolated from the roots and rhizome of 

Picrorhiza kurroa Rogle ex Benth. (Scrophulariaceae ), 

an Indian plant used for the treatment of liver 

diseases. [387] Protective activity of kutkin was demonstrated 

against the hepatic damage of A. phalloides in 

rodent models. [388,389] Floersheim found the protective 

effect of kutkin comparable to that of silybin. [390] 

Constituents from P. kurroa have demonstrated antioxidant 

and anti-lipid peroxidation activity as well as 

effects on liver regeneration in research cited by 

Luper. [313] Further investigations should be carried out 



to assess the place of kutkin in clinical amatoxin 

poisoning treatment. 

In vitro production and cytoprotective properties of 

polyclonal amanitin-specific antibodies were reported in 

1993. [391] However, Faulstich et al. [392] reported in 1998 

that amatoxin-specific Fab fragments or monoclonal 

antibodies enhanced the activity of amatoxins and that 

this new therapeutic strategy should not be considered. 

Retrospective Data on Use of Chemotherapy 


Our review of chemotherapy administered to 1632 

amatoxin poisoned patients underscores its typical use in 

combination, and makes it difficult to assess the efficacy 

of each therapeutic agent individually. The mechanism 

by which b-lactam antibiotics (benzylpenicillin, ceftazidime) 

afford their therapeutic effect is still scientifically 

uncharacterized. Considerable data support the relevance 

of silymarin complex in amatoxin poisoning; the 

mechanisms of action include an antioxidant effect, 

anti-lipid oxidation, enhancement of detoxication, and 

stimulation of the hepatic regeneration. Biochemical data 

suggesting hepatoprotection by antioxidants support the 

continued consideration of free radical scavengers such 

as ascorbic acid, cimetidine, and NAC in the management 

of amatoxin intoxication. Hepatoprotective effects 

of iridoid glycosides (aucubin, kutkin) have also been 

demonstrated with in vivo animal models; these 

promising findings merit further investigations. 

In our compilation, 80.9% (1632 of 2017) amatoxin 

poisoned patients received chemotherapy (Chem-group) 

with or without detoxication procedures (Tables 3–6). 

Drugs were given as mono-chemotherapy in 347 cases 

(21.3%, Table 3) and in combination in 1285 cases 

(78.7%, Tables 4–6) either as bi-chemotherapy (815 of 

1632, 49.9%) or tri-chemotherapy (280 of 1632, 17.2%) 

or poly-chemotherapy (190 of 1632, 11.6%). The 

therapeutic agents can be classified into four groups 

according to the frequency of their administration as 

single agent or chemotherapy combinations. Frequency 

of use ranged from 0.7 to 86.5%. The lowest frequencyof-use 

group among the 1632 amatoxin poisoning cases 

is constituted by ceftazidime (0.7%), cimetidine (1.1%), 

and antiseptic agent (1.2%). The second group is 

represented by vitamin C (3.7%), antibiotics (3.8%), 

and NAC (11.8%). The third group consists of thioctic 

acid (27.1%), steroids (27.6%), and silybin (33.7%). The 

highest frequency-of-use group is comprised of cases 

treated with benzylpenicillin (1411 of 1632 patients, 

86.5%). Benzylpenicillin was the most frequently 

administered drug used alone (164 cases, 10.1%,

Table 3) when compared to antibiotic (one case), 

cimetidine (three cases), NAC (89 cases), silybin (74 

cases), and steroids or thioctic acid (eight cases for each). 

It is also the agent most frequently represented in therapy 

combinations (1247 cases of 1632, 76.4%, Tables 4 and 

6). The most common combinations were benzylpenicillin 

plus silybin (379 of 1632, 23.2%) and benzylpenicillin 

plus thioctic acid (207 of 1632, 12.0%), in 

contrast to the low representation of benzylpenicillin plus 

steroid (95 of 1632, 5.8%). 

Retrospective Data on Use of Specific 


Specific treatments consist of detoxication procedures 

and chemotherapy. In our review, 2017 of 2108 

amatoxin-poisoned patients (95.7%) were treated with 

either one or both of these specific therapeutic modes. 

Detoxication procedures alone were applied to 385 of 

2017 cases (19.1%, Table 2) whereas chemotherapy with 

or without detoxication procedures was administered to 

the majority of cases (1632 of 2017, 80.9%, Tables 3–6). 

Overall survivors (1810 of 2017 patients, 89.7%) as 

listed in Tables 2–6 are subsequently analyzed for the 

relation to specific therapy and to LT. 

Liver Transplantation 

Liver transplantation has emerged as the most 

important advance in the therapy of FHF and is an 

intervention formally validated for this disease with 

survival rates from 60 to 80%. [282,393] Kinetic studies 

have shown no risk of toxicity for the transplanted 

liver [257] beginning day 4 after mushroom ingestion. 

Total Orthotopic Liver Transplantation and 

Auxiliary Partial Liver Transplantation 

Two surgical options, orthotopic liver transplantation 

(OLT) and auxiliary LT have been developed. Total OLT 

is a well-established procedure for FHF but requires long 

immunosuppression to maintain the graft. Because some 

patients with partial hepatectomy and temporary support 

may have complete morphological and functional 

recovery of their own liver, auxiliary partial liver 

transplantation (APOLT) represents an alternative. In 

APOLT only a portion of the native liver is removed and 

the remainder is left in situ; the transplant provides 

temporary assistance until the native liver recovers and 

the immunosuppression can be withdrawn. 

[394 – 397] 

Within the 20-year period of this review, 31 amatoxin 

poisoned patients underwent OLT: Six received suppor- 




tive measures alone (Table 1), six were treated with 

detoxication procedures without chemotherapy (Table 2), 

and 19 received chemotherapy with or without 

detoxication procedures (Tables 3–6). The success of 

APOLT in one young girl was also reported, [119,120] 

(Table 3). These 32 LT patients represent only 1.5% of 

2108 intoxicated cases reviewed in our survey. Twelve 

additional LT cases performed since 1985 were cited 

but due to lack of adequate data were not analyzed. 

[87,92,93,100,111,116,206,207,216,218,398,399] 

The early use of specific treatments (detoxication 

procedures and chemotherapy) and of biological 

parameters predicting recovery may avoid unnecessary 

LT. [146,159,187 – 189] Many patients who originally were 

candidates for LT showed improvement in hepatic 

function and were taken off the transplant waiting 

list. [83,156,158,159] 

The major dilemma in emergency liver failure is the 

right moment to transplant. The time between “too early” 

and “too late” may be very short. LT is considered too 

late when complications such as multi-organ failure with 

cerebral edema or renal insufficiency become contraindications 

to transplant because they compromise the 

success of surgery. The mean delay (about 2 days) 

between the decision for LT and finding of a liver donor 

must be taken into account. The shortage of available 

livers limits transplantation. Recently, a living, related 

donor of a 1-year-old boy poisoned with amatoxin 

provided a partial liver transplant specimen. [57] Fulminant 

hepatitis is rapidly fatal; only 50–85% of patients 

identified as candidates for LT survive long enough to 

receive a transplant. [400,401] An explosive course was also 

reported for amatoxin poisoned patients included in the 

emergency list for LT who died before obtaining a 

donor. [89,118,138,188,203] 

It is essential to establish early, reliable criteria 

identifying the immediate prognosis. [402,403] The number 

of amatoxin poisoning victims considered for LT is small 

and the prognostic indicators for LT are not clearly 

defined. [120] Candidacy guidelines for OLT and APOLT 

have therefore been extrapolated from experience with 

FHF from other etiologies and include repeated clinical 

examination and biological investigations. [404] 

Prognostic Factors 

Most liver units have accepted for emergency liver 

transplant the King’s College criteria proposed by 

O’Grady et al. [405] from a retrospective analysis of 278 

patients with FHF not induced by acetaminophen 

overdose. These criteria are based on PT, age, etiology,

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 



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 


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]

Table 7 

Prognosis Factors for Liver Transplant 

Coagulation Factors 




Date/References No. of cases Encephalopathy Stage P.T. Factor V(%) Lactic Acidosis Hypoglycemia (mg/dL) Hyperbilirubinemia a (mmol/L) 

1985 [193] 1/1; child III coma 34.2 sec NI NI 161 39.3 

1988 [136] 1/1 Coma ,20% ,20 NI NI 180 

1989 [80] 1/1; child III–IV ,10% ,20 NI NI NI 

1989 [102] 1/2 III 50 sec NI NI NI 427.3 

1/2 III 30 sec NI NI NI 341.9 

1990 [151] 2/4 I 81 sec NI þ þ 208.9 

2/4 II 81 sec NI þ þ NI 

1991 [103] 1/1 IV coma ,10% ,10 þ þ NI 

1992 [199] 1/1 III–IV .100 sec NI NI þ 556.5 

1994 [156] 1/1 I–II ,9% 6 NI NI 136.8 

1994 [106] 1/1 IV 28% b 

32 NI NI 364 

1994 [198] 1/1 I ,10% ,8 NI NI NI 

1995 [86] 2/2; 1 child II–III ,10% ,10 NI NI NI 

1995 [154] 1/1 III–IV ,10% b 

NI NI NI 144 

1996 [133] 2/2 II ,10% ,10 No prognosis values 

1997 [88] 3/3 III–IV ,20% NI NI NI 78.6 

1997 [91] 1/1 II–III 47.3 sec NI NI NI 124.8 

2000 [112] 1/1 III–IV 106 sec NI NI 19 158.9 

2001 [162] 2/2; 1 child NI 49 sec 7 NI NI 49.7 

29.1 sec 15 NI NI NI 

P.T. ¼ prothrombin test (sec) or (%); NI ¼ not indicated; þ¼presence. 

a 

Normal bilirubinemia level ranges from 2 to 17 mmol/L. 

b Thrombotest (factors II, VII, and X).

738 

Age of Patient 

The age of the amatoxin mushroom victim is another 

prognostic factor. Fatal outcomes are usually associated 

with age less than 10 years. [112,244] In the series of 205 

and 83 patients reported by Floersheim et al., [298] and 

Lambert and Larcan, [19] the death rates were 51 and 22% 

for children below 10 years and 16.5 and 8.8% for adults, 

respectively. The high mortality rate in children is likely 

related to the larger dose of the toxins per unit of body 

weight. 

Retrospective Liver Transplantation Data 

In the absence of definitive medical treatment for 

amatoxin poisoning, LT has changed the outlook for 

severe poisoning and can be the single best option 

for selected patients. Since 1985, 32 LTs (31 OLT and 1 

APOLT) have been performed for amatoxin mushroom 

victims representing 1.5% of 2108 intoxicated individuals. 

Liver transplant increases the survival rate of 

amatoxin poisoning considering the LT patient was 

presumed as a fatal case. Easily applicable criteria are 

needed to identify patients for whom transplantation is 

indicated. Prognostic indicators such as encephalopathy 

stages, coagulation factors, metabolic abnormalities, and 

age have to be taken into account in the decision to 

perform liver transplant (OLT and APOLT) but do not 

replace intensive medical experience. Serious amatoxin 

intoxication must no longer be considered only as an 

acute disease with massive necrosis whose prognosis 

depends only on the early course of the poisoning. The 

progression of severely poisoned cases towards either 

massive necrosis or chronic active hepatitis from 20 to 

70% [176,177] should be considered factors determining 

LT. 

Statistical Analysis of Retrospective Data 

Two general frequency tables were established 

including and excluding the LT cases, and composed 

for a systematic analysis. Statistical comparison of the 

2 £ 2 tables determined significant differences in the 

mortality rates of the 11 modes of care; the applied 

treatments were sorted by increasing efficacy, i.e., 

decreasing mortality rates (MR) combining MRLTi and 

MRLTe. Table 8 shows the 11 modes of care in order of 

increasing efficacy/decreasing mortality rates from #1 to 

#11 and the number of cases in each group including and 

excluding the liver transplanted patients with the related 

mortality rates. Then to further evaluate significant 

comparison between the 11 analyzed therapeutic 




modalities (#1 to #11), five pooled therapies from #12 

to #16 have made up. 

The mortality rates of the 10 analyzed specific 

therapeutic modes varied from 5.4 to 16.9% (MRLTi) 

and from 1.4 to 16.9% (MRLTe) for the 2062 LTi and 

2031 LTe amatoxin victims, respectively. Mortality rates 

were 47.3% ðNo: ¼ 91 LTiÞ and 43.5% ðNo: ¼ 85 LTeÞ 

for amatoxin poisoned patients receiving supportive 

measures alone (Fig. 1). 

First, the mortality rates of supportive measures alone 

(#11) were significantly higher than those found for the 

group of combined 10 specific therapies (#14, detoxication 

procedures plus nine chemotherapies) as reported in 

Tables 8 and 9. Then, the MR of detoxication procedures 

(#5) compared with #13, the nine combined chemotherapies, 

were not statistically different, but were significantly 

lower than those of two chemotherapies: 

BpThioca (#1) and BpwSilybTriPoly (#2). More 

importantly, the MRLTe of detoxication-proceduresalone 

(#5) was significantly higher than those of silybin 

plus benzylpenicillin (#8) and silybin (#10) as monochemotherapy 

(9.0 vs. 6.0 and 1.4%, respectively). 

Finally, the differences between the 9 individual applied 

chemotherapies were evaluated. The chemotherapies 

exhibiting the highest mortality rates were the combination 

of benzylpenicillin and thioctic acid (#1. 

BpThioca) followed by benzylpenicillin in drug 

combinations without silybin as tri- and poly-chemotherapies 

(#2. BpwSilybTriPoly), and by the combination 

of benzylpenicillin and steroids (#3. BpSter). 

The chemotherapies with the lowest mortality rates 

were silybin as mono-chemotherapy (#10. Silyb) and 

silybin plus benzylpenicillin without and with other 

drugs (#8. BpSilyb, #9. BpSilybTriPoly) and NAC as 

mono-chemotherapy (#7. NAC). Both MRLTi and 

MRLTe of BpThioca (#1), BpwSilybTriPoly (#2), and 

BpSter (#3) were not statistically different between them 

(Table 9), and were significantly higher than those of 

BpSilyb (#8), BpSilybTriPoly (#9), and Silyb (#10). 

Moreover no significant difference was observed 

between the MR of the four best therapies with the lowest 

mortality rates: NAC (#7), BpSilyb (#8), BpSilybTriPoly 

(#9), and Silyb (#10). The MR of #6, benzylpenicillin 

plus one or more antioxidant drug (cimetidine, NAC, or 

vitamin C), were significantly lower only than those of 

BpThioca (#1). The MR of NAC (#7) were significantly 

lower than those of both BpThioca (#1) and BpwSilyb- 

TriPoly (#2). 

On the other hand, the statistical data were not 

significant for certain treatment groups whose mortality 

rates appear to be different in part due to the disparity of

the group size and the small number of analyzed cases: 

(i) the MRLTs of benzylpenicillin as mono-chemotherapy 

(#4) were not statistically different from those of 

NAC (#7) and (ii) the MRLT of mono-chemotherapies, 

benzylpenicillin (#4), and silybin (#10) was comparable, 

11.6 vs. 5.4%, whereas the MRLTe of benzylpenicillin 

was significantly higher than that of silybin, 11.0 vs. 

1.4% (Table 9). Furthermore, benzylpenicillin plus 

antioxidant (#6. BpantiOx, No: ¼ 111 LTi treated; 

MRLTi 9.1%; No: ¼ 110 LTe treated; MRLTe 8.2%) 

was not statistically different from benzylpenicillin plus 

other drugs without silybin as tri- and poly-chemotherapies 

(#2. BpwSilybTriPoly, No: ¼ 299 LTi treated; 

MRLTi 15.4%; No: ¼ 297 LTe treated; MRLTe 

14.8%): the Chi-square values were 0.08 and 0.06, 

respectively; more data are needed to prove whether any 

statistical differences in the fatality rate between these 

groups were truly. 

To further assess the role of silybin in affecting 

mortality, the three chemotherapies with the worst 

mortality rates (#16. BpThioca, BpwSilybTriPoly and 

BpSter) were pooled and compared with the pooled 

therapies including silybin (#12. BpSilyb and BpSilybTriPoly); 

the MR of #12 were significantly lower 

than those of #16 (MRLTi 7.9 vs. 15.8% and MRLTe 




Table 8 

Statistical Analysis of Amatoxin-Poisoning Therapies 

5.8 vs. 15.5%). This finding supports silybin benefit in 

amatoxin poisoning treatment. 

Regarding benzylpenicillin, the most frequently 

therapeutic agent used among the reported cases, the 

bi-chemotherapies with this drug and without silybin 

were pooled (#15. BpThioca, BpSter, and BpantiOx), 

the MR found for this group were significantly higher 

than those of BpSilyb (#8) as reported in Table 9. In 

addition, the MR of BpwSilybTriPoly (#2) were 

significantly higher than those of BpSilybTriPoly (#9) 

(MRLTi 15.4 vs. 7.3%; MRLTe 14.8 vs. 5.4%). All 

these results suggest that benzylpenicillin administered 

with any drug except silybin as bi-, tri-, and polychemotherapies 

was not beneficial in treatment of 

amatoxin poisoning when mortality and/or liver 

transplant was used as the endpoint. 

Our statistical analysis underscores that the hepatoprotective 

effect of the flavonolignan complex, silymarin, 

and the antioxidant property of NAC play a 

crucial role in the recovery of amatoxin-poisoned 

patients. The limitations of this data include its 

retrospective nature and the lack of standardized severity 

scoring by which to judge the patient mix in each 

treatment group. However, these analyses and literature 

review point out the most fruitful avenues for future 

# No. LTi No. LTe MRLTi (%) MRLTe (%) 

Applied therapies 

1 BpThioca 207 207 16.9 16.9 

2 BpwSilybTriPoly 299 297 15.4 14.8 

3 BpSter 95 95 14.7 14.7 

4 Bp 164 163 11.6 11.0 

5 Detox alone 385 379 10.4 9.0 

6 BpantiOx 111 110 9.1 8.2 

7 NAC 89 89 6.7 6.7 

8 BpSilyb 391 382 8.2 6.0 

9 BpSilybTriPoly 151 148 7.3 5.4 

10 Silyb 74 71 5.4 1.4 

11 Supportive measures alone 91 85 47.3 43.5 

Pooled therapies 

12 Bp/Silybin combinations (8, 9) 542 530 7.9 5.8 

13 Combined nine chemotherapies (1–4, 6–10 above) 1586 1,567 11.2 10.1 

14 Combined 10 specific therapies (1–10 above) 2062 2,031 12.6 11.3 

15 Bp bi-chemotherapies without Silybin (1, 3, 6) 413 412 14.3 14.1 

16 Combined three worst chemotherapies (1–3) 601 599 15.8 15.5 

No. LTi ¼ number of patients including liver transplants; No. LTe ¼ number of patients excluding liver transplants; MRLTi ¼ mortality rate including 

liver transplants; MRLTe ¼ mortality rate excluding liver transplants.

740 

Figure 1. Effect of the modes of care (supportive measures 

alone and 10 specific treatments) on the distribution of treated 

patients in terms of survivors and deceased (histograms 

including liver transplants), and percentages of deceased 

patients vs. treated with and without liver transplants (curves). 

survLT: survivors including liver transplants; decLT: deceased 

including liver transplants; MRLTi: mortality rate including 

liver transplants; MRLTe: mortality rate excluding liver 

transplants. Supportive M. ¼ supportive measures alone 

(Table 1); BpThioca ¼ benzylpenicillin/thioctic acid; Bpw- 

SilybTriPoly ¼ benzylpenicillin/drugs without silybin as triand 

poly-chemotherapies; BpSter ¼ benzylpenicillin/steroid; 

Bp ¼ benzylpenicillin; Detox ¼ detoxication procedures alone 

(Table 2); BpantiOx ¼ benzylpenicillin/antioxidant drug 

(cimetidine, N-acetylcysteine or vitamin C); Nac ¼ 

N-Acetylcysteine; BpSilyb ¼ benzylpenicillin/silybin; 

BpSilybTriPoly ¼ benzylpenicillin/drugs with silybin as triand 

poly-chemotherapies; Silyb ¼ silybin. 

clinical research to pursue, and provide a basis for the 

discontinuation of the clearly less effective therapies. 

Investigations for amatoxin treatment should focus on 

detoxication procedures, silybin, and NAC. Assessment 

of more cases would be useful to confirm their benefit. 

Clinical data from this 20-year period do not show 

benzylpenicillin to be an effective drug; this antibiotic 

agent did not enhance the efficacy of either silybin or 

NAC in the treatment of amatoxin syndrome. Perhaps 

benzylpenicllin, thioctic acid, and steroids should be 

abandoned as therapeutic modalities. 



SUMMARY 


Although the treatment of patients exposed to 

amatoxin-containing mushrooms has become more 

sophisticated, the optimal management of the poisoning 

is still not determined. Options include various detoxication 

procedures, chemotherapies, and liver transplant in 

case the hepatic disease reaches a potentially fatal stage. 

The clinical efficacy of any modality of treatment for 

amatoxin poisoning is difficult to demonstrate since 

randomized, controlled clinical trials verified within the 

frame of multicenter studies have not been reported. The 

use of drug combinations also limits the evaluation of 

individual efficacy of the therapeutic modalities. The 

theoretical and experimental bases for antitoxic action of 

most of these agents are not clearly established. Silymarin 

complex and free radical scavengers (cimetidine, NAC, 

vitamin C) have respective hepatoprotective and antioxidant 

properties that yield convincing support for their use. 

LT is accepted as a life-saving procedure in amatoxin 

poisoning cases leading to acute massive hepatic 

necrosis. Early identification of liver dysfunction, rapid 

evaluation of suitability for transplant, immediate listing, 

and an available donor research are crucial. It is 

important to verify that the prognostic indications for LT 

are defined and met. 

Our retrospective data determined the use and the 

mortality rate for each treatment in this overall 

compilation of heterogeneous subjects. For statistical 

analysis relative to MR, the 32 amatoxin victims 

receiving LT were considered as special cases and 

were either excluded from the group of treated patients 

(MRLTe), or since their outcome was considered 

virtually fatal without transplantation, were included as 

deadly cases (MRLTi). 

Benzylpenicillin, despite mechanism of its action 

poorly argued, was the most frequently administered 

agent (86.5%). Silybin was given to 38.2% of patients. 

Among the antioxidant drugs, NAC was the most 

frequently prescribed agent, utilized in 11.8% of cases. 

Comparison of the mortality rates of 11 modes of care 

representing sufficient numbers of patients for statistical 

analysis showed that supportive measures alone resulted 

in high mortality comparable to historical data (.40%). 

The mortality rates of detoxication procedures alone 

were comparable to those of the nine combined 

chemotherapies suggesting a benefit due to amatoxin 

removal after initial absorption. Case data and numbers 

were insufficient to allow a comparison of the MR of the 

nine chemotherapies used with and without detoxication

Table 9 

Comparison of Mortality Rates Relative to the Different Therapies of the Amatoxin-Poisoning: (a) Including Liver Transplants (MRLTi) and (b) Excluding Liver 

Transplants MRLTe 

# Therapies 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 




(a) Including liver transplants (MRLTi) 

1. BpThioca 16.9 * * * ** * * ** 

2. BpwSilybTriPoly 15.4 * * ** ** * ** 

3. BpSter 14.7 * ** * ** 

4. Bp 11.6 ** 

5. Detox alone * * 10.4 ** 

6. BpantiOx * 9.1 ** 

7. NAC * * 6.7 ** 

8. BpSilyb ** ** * 8.2 ** ** 

9. BpSilybTriPoly * ** ** 7.3 ** 

10. Silyb * * * 5.4 ** 

11. Supportive measures alone ** ** ** ** ** ** ** ** ** ** 47.3 ** ** ** ** ** 

12. Bp combinations with Silybin (8, 9) ** 7.9 ** 

13. Combined nine chemotherapies (1–4, 6–10 above) ** 11.2 

14. Combined 10 specific therapies (1–10 above) ** 12.6 

15. Bp bi-chemotherapies without Silybin (1, 3, 6) ** ** 14.3 

16. Combined three worst chemotherapies (1–3) ** ** 15.8 

(b) Excluding liver transplants (MRLTe) 

1. BpThioca 16.9 ** * * ** * ** ** 

2. BpwSilybTriPoly 14.8 * * ** ** ** ** 

3. BpSter 14.7 ** ** ** ** 

4. Bp 11.0 * ** 

5. Detox alone ** * 9.0 * * ** 

6. BpantiOx * 8.2 ** 

7. NAC * * 6.7 ** 

8. BpSilyb ** ** ** * 6.0 ** ** 

9. BpSilybTriPoly * ** ** 5.4 ** 

10. Silyb ** ** ** * * 1.4 ** 

11. Supportive measures alone ** ** ** ** ** ** ** ** ** ** 43.5 ** ** ** ** ** 

12. Bp combinations with Silybin (8, 9) ** 5.8 ** 

13. Combined nine chemotherapies (1–4, 6–10 above) ** 10.1 

14. Combined 10 specific therapies (1–10 above) ** 11.3 

15. Bp bi-chemotherapies without Silybin (1, 3, 6) ** ** 14.1 

16. Combined three worst chemotherapies (1–3) ** ** 15.5 

Significant comparisons of mortality rates (*: p # 0:05; **: p # 0:01Þ;1. 5 (MRLTi*, MRLTe**); 1 . 6 and 1 . 7 (MRLTi*, MRLTe*); 1 . 8 (MRLTi**, MRLTe**); 1 . 9 (MRLTi*, 

MRLTe*); 1 . 10 (MRLTi*, MRLTe**); 2 . 5 (MRLTi*, MRLTe*); 2 . 7 (MRLTi*, MRLTe*); 2 . 8 (MRLTi**, MRLTe**), 2 . 9 (MRLTi**, MRLTe**); 2 . 10 (MRLTi*, 

MRLTe**); 3 . 8 (MRLTi*, MRLTe**); 3 . 9 (MRLTi**, MRLTe**); 3 . 10 (MRLTi*, MRLTe**); 4 . 10 (MRLTe*); 5 . 8 and 5 . 10 (MRLTe*); 11 . 1 to 10 (MRLTi**, 

MRLTe**); 12 . 16 (MRLTi**, MRLTe**); 15 . 8 (MRLTi**, MRLTe**); 16 . 8 (MRLTi**, MRLTe**).

742 

procedures in order to assess a beneficial toxin 

elimination for each applied chemotherapy. 

A ranking of therapies was based on significant 

differences in effectiveness as measured by decreasing 

mortality rates (Fig. 1, Tables 8 and 9). The highest 

mortality/lowest efficacy was observed with combinations 

of benzylpenicillin with thioctic acid, steroid, 

and other drugs except silybin as bi-, tri-, and polychemotherapies. 

The lowest mortality rates were 

observed with silybin and NAC both administered as 

mono-chemotherapy, and silybin associations with 

benzylpenicillin as bi, tri-, and poly-chemotherapies. 

Since no significant difference between silybin singly 

and silybin/benzylpenicillin combinations was found, 

it appears that the flavonolignan complex is effective 

in reducing mortality and/or avoid LT whereas 

benzylpenicillin singly is ineffective. Similarly, NAC 

statistically appears to be a potentially more effective 

chemotherapy than the other drug options. 

Review of the modes of care reported for amatoxinintoxicated 

patients over the last 20 years demonstrates 

wide variability in treatment and response to treatment. 

Of particular interest in the environment of evidencebased 

medicine is the prevalent use of a therapy, 

benzylpenicillin, which has little theoretical foundation 

and little evidence of efficacy when compared to 

treatment alternatives. It exemplifies the fallacy of 

consensus judgments and recommendations based solely 

on widespread use of a treatment. These case analyses 

and literature review have a number of limitations due to 

the disparity in severity grades. However, our work 

suggests the most successful orientation for prospective 

clinical research and provides a basis for the discontinuation 

of the clearly less effective chemotherapies. 

Efficacy of several drugs is not supported in this review: 

the most widely used agent, benzylpenicllin, as well as 

thioctic acid and steroids; perhaps their use should be 

discontinued. Amatoxin poisoning cases whose treatment 

focuses on detoxication procedures, silybin, and 

NAC would be useful to confirm their relevance revealed 

by our statistical analysis. Future research should be 

directed towards the iridoid glycosides being potential 

agents to inhibit amatoxins and stimulate hepatocyte 

regeneration. 

ACKNOWLEDGMENTS 

The authors are grateful to J. ApSimon (Canada), 

S. Badalian (Armenia), R. Courtecuisse (France), 

J. Elguero (Spain), G. Eyssartier (France), E. Florac 



(France), F. Fons (France), A. Fraiture (Belgium), 

J. Guillot (France), D. Guez (Japan), J. Guinberteau 

(France), G. Guzman (Mexico), M. Heil (Germany), 

G. Konska (Poland), M. J. Mauruc (France), J. Melot 

(Iceland), P. A. Moreau (France), and G. Redeuilh 

(France) for providing literature data. 

REFERENCES 


1. De Haro, L.; Prost, N.; Perringue, C.; Arditti, J.; David, 

J.M.; Drouet, G.; Thomas, M.; Valli, M. Intoxications 

par Champignons: Expérience du Centre Anti-Poisons 

de Marseille en 1994 et 1998. Bull. Épidémiol. 

Hebdomadaire 1999, 30, 1–8. 

2. Jacobs, J.; VonBehren, J.; Kreutzer, R. Serious Mushroom 

Poisonings in California Requiring Hospital 

Admission, 1990–1994. West. J. Med. 1996, 165, 

283–288. 

3. Litovitz, T.L.; Clark, L.R.; Soloway, R.A. 1993 Annual 

Report of the American Association of Poison Control 

Centers Toxic Exposure Surveillance System. Am. 

J. Emerg. Med. 1994, 12 (5), 546–584. 

4. Litovitz, T.L.; Felberg, L.; Soloway, R.A.; Ford, M.; 

Geller, R. 1994 Annual Report of the American Association 

of Poison Control Centers Toxic Exposure Surveillance 

System. Am. J. Emerg. Med. 1995, 13 (5), 551–597. 

5. Litovitz, T.L.; Felberg, L.; White, S.; Klein-Schwartz, 

W. 1995 Annual Report of the American Association of 

Poison Control Centers Toxic Exposure Surveillance 

System. Am. J. Emerg. Med. 1996, 14 (5), 487–537. 

6. Litovitz, T.L.; Smilkstein, M.; Felberg, L.; Klein- 

Schwartz, W.; Berlin, R.; Morgan, J.L. 1996 Annual 



J. Emerg. Med. 1997, 15 (5), 447–500. 

7. Litovitz, T.L.; Klein-Schwartz, W.; Dyer, K.S.; Shannon, 

M.; Lee, S.; Powers, M. 1997 Annual Report of the 

American Association of Poison Control Centers Toxic 

Exposure Surveillance System. Am. J. Emerg. Med. 

1998, 16 (5), 443–497. 

8. Litovitz, T.L.; Klein-Schwartz, W.; Caravati, E.M.; 

Youniss, J.; Crouch, B.; Lee, S. 1998 Annual Report of 

the American Association of Poison Control Centers 

Toxic Exposure Surveillance System. Am. J. Emerg. 

Med. 1999, 17 (5), 535–587. 

9. Litovitz, T.L.; Klein-Schwartz, W.; White, S.; Cobaugh, 

D.J.; Youniss, J.; Drab, A.; Benson, B.E. 1999 Annual 



J. Emerg. Med. 2000, 18 (5), 517–574. 

10. Persson, H.E.; Sjöberg, G.K.; Haines, J.A.; Pronczuk de 

Carbino, J. Poisoning Severity Score. Grading of Acute 

Poisoning. Clin. Toxicol. 1998, 36 (3), 205–213.




11. Trestail, J.H. Mushroom Poisoning in the United 

States—An Analysis of 1989 United States Poison 

Center Data. Clin. Toxicol. 1991, 29 (4), 459–465. 

12. Bresinsky, A.; Besl, H. A Colour Atlas of Poisonous 

Fungi; Wolfe Publishing Ltd.: Stuttgart, Germany, 1990; 

295. 

13. Fanton, L.; Perrot, D.; Miras, A.; Achache, P.; Malicier, 

D. Intoxications par les Champignons. Rev. Prat. 1995, 

45, 1327–1332. 

14. Faulstich, H.; Zilker, T. Amatoxins. In Handbook of 

Mushroom Poisoning, Diagnosis and Treatment; 

Spoerke, D.G., Rumack, B.H., Eds.; CRC Press, Inc.: 

Boca Raton, FL, 1994; 233–248. 

15. Godfrank, L.R. Mushrooms: Toxic and Hallucinogenic. 

In Godfrank’s Toxicologic Emergencies; Godfrank, 

L.R., Ed.; Appleton & Lange: Norwalk, CT, 1998; 

1205–1219. 

16. Jaeger, A.; Vale, J.A. Intoxications Aiguës; Elsevier: 

Paris, 1999; 393–415. 

17. Kohn, R.; Motovska, Z. Otrava Hubami—Klasifikacia, 

Symptomatoza a Liecba (Mushroom Poisoning— 

Classification, Symptomatology and Treatment). Vnitr. 

Lék. 1997, 43 (4), 230–233. 

18. Lambert, H. Le Syndrome Phalloïdien. Les Intoxications 

Aiguës, Collection Anesthésie et Réanimation 

d’Aujourd’hui; Arnette: Paris, France, 1993; 495–517. 

19. Lambert, H.; Larcan, A. Intoxications par les Champignons. 

Encyclopédie Médico-Chirurgicale; Elsevier 

Publishers/Editions Scientifiques et Médicales: Paris, 

France, 1989; Vol. 3, 1–14. 

20. Larcan, A. A Propos de la Néphropathie Phalloïdienne. 

Presse Méd. 1999, 28 (5), 231. 

21. Vetter, J. Toxins of Amanita phalloides (Review). 

Toxicon 1998, 36 (1), 13–24. 

22. Wiernikowski, A.; Sczepanek, M. Zatrucie Muchomoren 

Sromotnikowym—Rozpoznawanie, Klinika, Leczenie 

(Amanita phalloides Poisoning—Diagnosis, Clinical 

Course, Treatment). Przegl. Lék. 1999, 56 (6), 450–454. 

23. Zachoval, R.; Günther, C.; Scheurlen, C.; Klüppelberg, 

U.G.; Zilker, T.; Pape, G.R. Ein 27Jähriger Patient mit 

Wäßrigen Durchfällen, Ubelkeit und Erbrechen 10 h 

nach Genuß Eines Pilzgerichtes. Internist 1994, 35, 

385–391. 

24. Fineschi, V.; Di Paolo, M.; Centini, F. Histological 

Criteria for Diagnosis of Amanita phalloides Poisoning. 

J. Forensic Sci. 1996, 41 (2), 429–432. 

25. Ammirati, J.F.; Traquair, J.A.; Horgen, P.A. Poisonous 

Mushrooms of Canada Including Other Inedible Fungi; 

Fitzhenry & Whiteside: Markham, Canada, 1985; 396. 

26. Lincoff, G.H. National Audubon Society Field Guide to 

North American Mushrooms; Alfred A. Knopf: New 

York, 1998; 926. 

27. Enjalbert, F.; Cassanas, G.; Andary, C. Variation in 

Amounts of Main Phallotoxins in Amanita phalloides. 

Mycologia 1989, 81 (2), 266–271. 

28. Enjalbert, F.; Gallion, C.; Jehl, F.; Monteil, H.; 

Faulstich, H. Simultaneous Assay for Amatoxins and 

Phallotoxins in Amanita phalloides Fr. by High- 

Performance Liquid Chromatography. J. Chromatogr. 

A 1992, 598, 227–236. 

29. Enjalbert, F.; Gallion, C.; Jehl, F.; Monteil, H.; 

Faulstich, H. Amatoxins and Phallotoxins in Amanita 

Species: High-Performance Liquid Chromatographic 

Determination. Mycologia 1993, 85 (4), 579–584. 

30. Wieland, T. The Toxic Peptides from Amanita 

Mushrooms. Int. J. Pept. Protein Res. 1983, 22, 

257–276. 

31. Wieland, T.; Faulstich, H. Peptide Toxins from Amanita. 

In Handbook of Natural Toxins; Keeler, R.F., Tu, A.T., 

Eds.; Marcel Dekker, Inc.: New York, 1983; Vol. 1, 

585–635. 

32. Faulstich, H.; Wieland, T. New Aspects of Amanitin and 

Phalloidin Poisoning. In Natural Toxins II. Advances in 

Experimental Medicine and Biology; Singh, B.R., Tu, 

A.T., Eds.; Plenum Press: New York, 1996; 309–314. 

33. Wieland, T.; Faulstich, H. Fifty Years of Amanitin. 

Experientia 1991, 47, 1186–1193. 

34. Courtecuisse, R.; Duhem, B. Guide des Champignons de 

France et d’Europe; Delachaux et Niestlé: Lausanne, 

Switzerland, 2000; 476. 

35. Logemann, H.; Argueta, J.; Guzman, G.; Montoya Bello, 

L.; Bandela Munoz, V.; Leon Chocooj, R. Evenamiento 

Mortal por Hongos en Guatemala. Rev. Mex. Micol. 

1987, 3, 211–216. 

36. Trestail, J.H. Mushroom Poisoning Case Registry: North 

American Mycological Association Report 1991. 

McIlvainea 1992, 10 (2), 51–59. 

37. Benjamin, D.R. Mushrooms Poisons and Panaceas; 

Freeman, W.H. and Company: New York, 1995; 422. 

38. Besl, H. Amatoxins in Greenhouses, Galerina sulciceps, 

a Tropical Toxic Mushroom. Z. Mykol. 1981 (Received 

1982), 47 (2), 253–256. 

39. Singer, R. The Agaricales in Modern Taxonomy; Koeltz 

Scientific Books: Koenigstein, Germany, 1986; 981. 

40. Muraoka, S.; Fukamachi, N.; Mizumoto, K.; Shinozawa, 

T. Detection and Identification of Amanitins in the 

Wood-Rotting Fungi Galerina fasciculata and Galerina 

helvoliceps. Appl. Environ. Microbiol. 1999, 65 (9), 

4207–4210. 

41. Muraoka, S.; Shinozawa, T. Effective Production of 

Amanitins by Two-Step Cultivation of the Basidiomycete, 

Galerina fasciculata GF-060. J. Biosci. Bioeng. 

2000, 89 (1), 73–76. 

42. Pond, S.M.; Olson, K.R.; Woo, O.F.; Osterloh, J.D.; 

Ward, R.E.; Kaufman, D.A.; Moody, R.R. Amatoxin 

Poisoning in Northern California, 1982–1983. West. 

J. Med. 1986, 145 (2), 204–209. 

43. Piqueras, J. Nuevas Aportaciones al Conocimiento de la 

Etiologia, Fisiopatologia, Clinica y Terapeutica de las 

Intoxicaciones por Hongos Macromicetos Hepatotoxicos

744 



(Amanitas y Lepiotas). Tesis Doctoral, Universitat de 

Barcelona: Spain, 1988, 519. 

44. Klan, J. Prehleb hub Obsahujicich Amanitiny a 

Faloidiny (the Survey of Fungi Containing Amanitins 

and Phalloidins). Cas. Lék. Cesk. 1993, 132 (15), 

449–451. 

45. Esteve-Ravantos, F.; Altés, A. Tres Interesantes 

Lepiotas Toxicas en la Provincia de Madrid. Bol. Soc. 

Micol. Madrid 1990, 14, 161–168. 

46. Besl, H.; Mack, P.; Schmid-Heckel, H. Gifpilze in den 

Gattungen Galerina und Lepiota (New Toxic Fungi in 

the Genera Galerina and Lepiota ). Z. Mykol. 1984, 50 

(2), 183–192. 

47. Gérault, A. Les Champignons Supérieurs et Leurs 

Intoxications. Le Genre Lepiota (au sens Ancien 

Classique). Thèse d’Etat ès Sciences Pharmaceutiques, 

Université de Rennes: France, 1976, 302. 

48. Gérault, A.; Girre, L. Recherches Toxicologiques sur le 

Genre Lepiota Fries. C. R. Acad. Sci. Paris 1975, 280 

(25), 2841–2843. 

49. Gérault, A.; Girre, L. Mise au Point sur les Intoxications 

par les Champignons Supérieurs. Bull. Soc. Mycol. Fr. 

1977, 93 (3), 373–405. 

50. Piqueras, J. Hepatotoxic Mushroom Poisoning: Diagnosis 

and Management. Mycopathologia 1989, 105, 

99–110. 

51. Piqueras, J. Terapeutica de la Intoxicacion por Amanita 

phalloides. Farm. Clin. 1992, 9 (3), 221–228. 

52. Brady, L.R.; Benedict, R.G.; Tyler, D.E.; Stuntz, D.E.; 

Malone, M.H. Identification of Conocybe filaris as a 

Toxic Basidiomycete. Lloydia 1975, 38, 172–173. 

53. Bertault, R. Amanites du Maroc. Bull. Soc. Mycol. Fr. 

1965, 81, 345–371. 

54. Bertault, R. Amanites du Maroc. Bull. Soc. Mycol. Fr. 

1980, 96, 273–284. 

55. Flegg, P.J. Mushroom Poisoning. Cent. Afr. J. Med. 

1981, 27 (7), 125–129. 

56. Reid, D.A.; Eicker, A. South African Fungi: The Genus 

Amanita. Mycol. Res. 1991, 95, 80–95. 

57. D’Agostino, D.E.; Garcia Roig, C.; Telenta, M.; Duca, 

P.; Steinberg, C.E.; de Santibanes, E. Liver Transplantation 

in Amanita phalloides Intoxication. Hepatology 

1998, 28, (2326) 744A. 

58. Villegas, M.; Cifuentes, J.; Aroche, R.M.; Fuentes, P. 

Primer Registro de Amanita phalloides en Mexico. Bol. 

Soc. Mex. Micol. 1982, 17, 140–146. 

59. Gurevich, L.S.; Zhurkovitch, I.K. Toxins of Some 

Species of the Genus Amanita Pers. Mikol. Fitopatol. 

1995, 29, 41–50. 

60. Lim, J.G.; Kim, J.H.; Lee, S.I.; Kim, Y.S. Amanita 

virosa Induced Toxic Hepatitis: Report of Three Cases. 

Yonsei Med. J. 2000, 41 (3), 416–421. 

61. Omidynia, E.; Rashidpourai, R.; Quaderi, M.T.; Ameri, 

E. Mycetismus in Hamadan of West Iran. Southeast 

Asian J. Trop. Med. Health 1997, 28, 438–439. 


62. Oztekin-Mat, A. Les Intoxications par les Champignons 

en Turquie. Ann. Pharm. Fr. 1998, 56, 233–235. 

63. Seeger, R.; Stijve, T. Occurrence of Toxic Amanita 

Species. In Amatoxin, Toxins and Poisonings; Faulstich, 

H., Kommerell, B., Wieland, T., Eds.; Lubrecht Cramer: 

New York, 1980; 3–17. 

64. Ying, J.; Mao, X.; Ma, Q.; Zong, Y.; Wen, H. Icones of 

Medicinal Fungi from China; Science Press: Beijing, 

China, 1987; 575. 

65. Yin, W.; Yang, Z.R. A Clinical Analysis of Twelve 

Patients with Galerina autumnalis Poisoning. Chunghua 

Nei K’o Tsa Chih 1993, 32 (12), 810–812. 

66. Zu, Y. Acute Mushroom Poisoning with Amanita virosa. 

Chung-hua Yu Fang I Hsueh Tsa Chih 1987, 21 (6), 

335–337. 

67. Edward, J.N.; Henry, J.A. Medical Problems of Mushroom 

Ingestion. Mycologist 1989, 3 (1), 13–16. 

68. Pegler, D.N.; Watling, R. British Toxic Fungi. Bull. Br. 

Mycol. Soc. 1982, 16, 66–75. 

69. Barbato, M.P. Poisoning from Accidental Ingestion of 

Mushrooms. Med. J. Aust. 1993, 158, 842–847. 

70. Cole, F.M. Amanita phalloides in Victoria. Med. J. Aust. 

1993, 158 (12), 849–850. 

71. Trim, G.M.; Lepp, H.; Hall, M.J.; McKeown, R.V.; 

McCaughan, G.W.; Duggin, G.G.; Le Couteur, D.G. 

Poisoning by Amanita phalloides (“deathcap”) Mushrooms 

in the Australian Capital Territory. Med. J. Aust. 

1999, 171 (5), 247–249. 

72. Chaiear, K.; Limpaiboon, R.; Meechai, C.; Poovorawan, 

Y. Fatal Mushroom Poisoning Caused by Amanita 

virosa in Thailand. Southeast Asian J. Trop. Med. Public 

Health 1999, 30 (1), 157–160. 

73. Hanrahan, J.P.; Gordon, M.A. Mushroom Poisoning: 

Case Reports and a Review of Therapy. J. Am. Med. 

Assoc. 1984, 251 (8), 1057–1061. 

74. Olson, K.R.; Pond, S.M.; Sewards, J.; Healey, K.; Woo, 

F.; Becker, C.E. Amanita phalloides-Type Mushroom 

Poisoning. West. J. Med. 1982, 137 (4), 282–289. 

75. Bauchet, J.M. Poisoning Said to Be Due to Galerina 

unicolor. Bull. Br. Mycol. Soc. 1983, 17, 51. 

76. Furia, A.; Bernicchia, A.; Alberton, F. Intossicazione 

Parafalloidea da Lepiota brunneoincarnata. Micol. Ital. 

1982, 3, 29–33. 

77. Calonge, F.D.; Lopez-Herce, J.A. Tres Casos de 

Envenenamiento Grave en Madrid por Ingestion de 

Lepiota brunneo-incarnata Chodat & Martin (Three 

Cases of Poisoning by Lepiota brunneo-incarnata 

Chodat & Martin in Madrid). Bol. Soc. Micol. Madrid 

1987, 11 (2), 287–290. 

78. Gúzman, G. Un Caso Especial de Evenamiento Mortal 

Producido por Hongos en el Estado de Veracruz. Rev. 

Mex. Micol. 1987, 3, 203–209. 

79. McClain, J.L.; Hausse, D.W.; Clark, M.A. Amanita 

phalloides Mushroom Poisoning: A Cluster of Four 

Fatalities. J. Forensic Sci. 1989, 34, 83–87.




80. Boudjema, K.; Wolf, P.; Burtscher, A.; Juif, J.G.; Steib, 

A.; Ellero, B.; Jaeck, D.; Cinqualbre, J. Hépatite 

Fulminante par Intoxication Phalloïdienne. Une Indication 

d’Allotransplantation Hépatique. Presse Méd. 

1989, 18 (18), 937. 

81. Isiloglu, M.; Watling, R. Poisoning by Lepiota helveola 

Bres. in Southern Turkey. Edinb. J. Bot. 1991, 48 (1), 

91–100. 

82. Paydas, S.; Kocak, R.; Erturk, F.; Erken, E.; Zaksu, H.S.; 

Gurcay, A. Poisoning Due to Amatoxin-Containing 

Lepiota Species. Br. J. Clin. Pharmacol. 1990, 44 (11), 

450–453. 

83. Ronzoni, G.; Vesconi, S.; Radrizzani, D.; Corbetta, C.; 

Langer, M.; Iapichino, G. Guarigione Dopo Intossicazione 

Grave da Funghi Selvatici (Encefalopatia di IV 

Grado) con Sola Terapia Medica Intensiva e Senza 

Trapianto di Fegato Caso Clinico. Minerva Anestesiol. 

1990, 57, 383–387. 

84. Pérez-Moreno, J.; Pérez-Moreno, A.; Ferrara-Cerrato, R. 

Multiple Fatal Mycetism Caused by Amanita virosa in 

Mexico. Mycopathologia 1994, 125 (1), 3–5. 

85. Pérez-Moreno, J.; Ferrera-Cerrato, R. A Review of 

Mushroom Poisoning in Mexico. Food Addit. Contam. 

1995, 12 (3), 355–360. 

86. Meunier, B.C.; Camus, C.M.; Houssin, D.P.; Messner, 

M.J.M.; Gérault, A.M.; Launois, B.G. Liver Transplantation 

After Severe Poisoning Due to Amatoxin- 

Containing Lepiota—Report of Three Cases. Clin. 

Toxicol. 1995, 33 (2), 165–171. 

87. Kern, C.; Zilker, T.; Van Clarman, M. Successful Liver- 

Transplantation in a Child After Amanita Poisoning. 

Congress of Anti-Poisons Centre, Istanbul, Turkey, May 

24–27, 1992; 37. 

88. Beckurts, K.T.E.; Hölscher, A.H.; Heidecke, C.D.; 

Zilker, T.R.; Natrath, W.; Siewert, J.R. Die Rolle der 

Lebertransplantation im Behandlungskonzept des Akuten 

Leberversagens nach Knollenblätterpilzvergiftung 

(The Place of Liver Transplantation in the Treatment of 

Acute Liver Failure Caused by Amanita phalloides Poisoning). 

Dtsch. Med. Wochenschr. 1997, 122, 351–355. 

89. O’Brien, B.L.; Khuu, L. A Fatal Sunday Brunch: 

Amanita Mushroom Poisoning in a Gulf Coast Family. 

Am. J. Gastroenterol. 1996, 91 (3), 581–583. 

90. Zevin, S.; Dempsey, D.; Olson, K. Amanita phalloides 

Mushroom Poisoning—Northern California, January 

1997. Morb. Mortal. Wkly Rep. 1997, 46 (22), 489–492. 

91. Skaare, V.K. Mushroom Poisoning: An Indication for 

Liver Transplantation. J. Transplant. Coord. 1997, 7 (3), 

141–143. 

92. Scocco, P.; Rupolo, G.; De Leo, D. Failed Suicide by 

Amanita phalloides (Mycetismus) and Subsequent Liver 

Transplant: Case Report. Arch. Suicide Res. 1998, 4, 

201–206. 

93. Cochran, K.W. 1999 Annual Report of the North 

American Mycological Association’s Mushroom 

Poisoning Case Registry. McIlvainea 2000, 14 (2), 

34–40. 

94. Chiossi, M.; Di Pietro, P.; Marchi, A.; Messi, G.; 

Gallone, G.; Peisino, M.G. Mushroom Poisoning in 

Children. Vet. Hum. Toxicol. 1993, 35 (4), 331. 

95. Elonen, E.; Härkönen, M. Myrkkynääpikän (Galerina 

marginata ) Aiheuttama Myrkytys (Poisoning with 

Galerina marginata ). Duodecim 1978, 94, 1050–1053. 

96. Belliardo, F.; Massano, G.; Accomo, S. Amatoxins 

Do Not Cross the Placental Barrier. Lancet 1983, 

1, 1381. 

97. Kendrick, B.; Shimizu, A. Mushroom Poisoning— 

Analysis of Two Cases and a Possible New Treatment, 

Plasmapheresis. Mycologia 1984, 76 (3), 448–453. 

98. Fort, J.; Rodriguez, J.A.; Cantarell, C.; Bartolomé, J.; 

Boveda, J.L.; Olmos, A.; Piera, L. Plasmaseparacion en 

la Intoxicacion por Amanita phalloides. Med. Clin. 

(Barc.) 1984, 82, 748–775. 

99. Boron, P.; Prokopowicz, D.; Miegoc, H. Plazmafereza w 

Leczeniu Zatruc Grzybami (Plasmapheresis in the 

Treatment of Poisoning with Mushrooms). Pol. Tyg. 

Lék. 1987, XLII (39), 1215–1219. 

100. DeSilvestro, G.; Marson, P.; Brandolese, R.; Pittoni, G.; 

Ongaro, G. A Single Institution’s Experience (1982– 

1999) with Plasma-Exchange Therapy in Patients with 

Fulminant Hepatic Failure. Int. J. Artif. Organs 2000, 

23 (7), 454–461. 

101. Ohrn, M.; Jörgensen, B.; Gréen, K.; Karlson-Stiber, C.; 

Persson, H. Amatoxinanalys vid Svampförgiftning 

(Amatoxin Analysis in Mushroom Poisoning). Laekartidningen 

1987, 84 (34), 2581–2583. 

102. Klein, A.S.; Hart, J.; Brems, J.J.; Goldstein, L.; Lewin, 

K.; Busuttil, R.W. Amanita Poisoning: Treatment and 

the Role of Liver Transplantation. Am. J. Med. 1989, 85, 

187–193. 

103. Pouyet, M.; Caillon, P.; Ducerf, C.; Berthaud, S.; 

Bouffard, Y.; Delafosse, B.; Thomasson, A.; Pignal, C.; 

Pulce, C. Transplantation Orthotopique du Foie pour 

Intoxication Grave par Amanite Phalloïde. Presse Méd. 

1991, 20 (41), 2095–2098. 

104. Gazzero, R.C.; Goos, R.D. A Case of Mushroom 

Poisoning Involving Amanita virosa. McIlvainea 1991, 

10 (1), 45–46. 

105. Pelclova, D.; Rakovcova, H. Intoxikace Houbou 

Amanita phalloides v Dotazech Toxikologickeho 

Informacniho Strediska v Praze (Mushroom Amanita 

phalloides in the Inquiries of the Poison Information 

Centre). Cas. Lék. Cesk. 1993, 132, 470–472. 

106. Doepel, M.; Isoniemi, H.; Salmela, K.; Penttilä, K.; 

Höckerstedt, K. Liver Transplantation in a Patient with 

Amanita Poisoning. Transplant. Proc. 1994, 26 (3), 

1801–1802. 

107. Karakullukçu, F.; Besler, M.; Yurdun, T.; Sifoglu, Z.; 

Yuksel, K.; Hacikaptan, E.; Onsun, K.; Karakullukçu, 

B. Hemoperfusion Is Life Saving in Amanita phalloides

746 

Intoxication. XXXIIIrd Congress of EDTA, Amsterdam, 

Holland, 1996; 316. 

108. Trestail, J.H. Mushroom Poisoning Case Registry: 

NAMA Report 1995. McIlvainea 1996, 12 (2), 98–104. 

109. Yamada, E.G.; Mohle-Boetani, J.; Olson, K.R.; Werner, 

S.B. Mushroom Poisoning Due to Amatoxin. West. 

J. Med. 1998, 169, 380–384. 

110. Langer, M.; Gridelli, B.; Piccolo, G.; Markovic, S.; 

Quarenghi, E.; Gatti, S.; Ghio, L.; Ginevri, F. A Liver- 

Transplant Candidate (Fulminant Hepatic Failure from 

Amanita phalloides Poisoning) as a Multiorgan Donor. 

Transplant. Proc. 1997, 29, 3343–3344. 

111. Splendiani, G.; Zazzaro, D.; Di Pietrantonio, P.D.; 

Delfino, L. Continuous Renal Replacement Therapy and 

Charcoal Plasmaperfusion in Treatment of Amanita 

Mushroom Poisoning. Artif. Organs 2000, 24 (4), 

305–308. 

112. Pomerance, H.H.; Barness, E.G.; Kobli-Kumar, M.; 

Arnold, S.R.; Steigelfest, J. A 15-Year-Old Boy with 

Fulminant Hepatic Failure. J. Pediatr. 2000, 137 (1), 

114–118. 

113. Jaros, F. Incidence of Fungal Intoxications Including 

Amanita phalloides in Last Four Decades in the District 

of Trencia in Slovakia. Ceska Mykol. 1992 (Received 

1993), 46 (3–4), 256–262. 

114. Jaros, F.; Simurka, P.; Ehsanova, M. Incidencia, Sucasna 

Liecba a Prognoza Otrav Hubami u Deti a Dospelych 

(Incidence, Contemporary Treatment and Prognosis of 

Mushroom Poisoning in Children and Adults). Cs. 

Pediatr. 1998, 53 (2), 90–93. 

115. Cosme Jimenez, A.; Zabaleta Arrizabalaga, S.; Izaguirre 

Boneta, A.; Diago Ferrero, A.; Alzate Saez de Heredia, 

L.F.; Orive Cura, V.; Arenas Mirave, J.I. Intoxication no 

Mortal por Amanita phalloides. A Proposito de dos 

Casos. Rev. Clin. Esp. 1983, 171 (4), 261–264. 

116. Montanini, S.; Sinardi, D.; Pratico, C.; Sinardi, A.U.; 

Trimarchi, G. Use of Acetyl-Cysteine as the Life-Saving 

Antidote in Amanita phalloides (Death Cap) Poisoning. 

Case Report on 11 Patients. Arzneim.-Forsch. 1999, 

49 (12), 1044–1047. 

117. Kacic, M.; Dujsin, M.; Puretic, Z.; Slavicek, J. 

Micetizam u Djece-u Povodu Jedne Epidemije Otrovanja 

(Mycetismus in Children, with Special Reference 

to One Outbreak of Mushroom Poisoning). Lijec. Vjesn. 

1990, 112 (11–12), 369–373. 

118. Trestail, J.H. Mushroom Poisoning Case Registry: 


119. Rosenthal, P.; Roberts, J.P.; Ascher, N.L.; Edmond, J.C. 

Auxiliary Liver Transplant in Fulminant Failure. 

Pediatrics 1997, 100 (2), 100–111. 

120. Rosenthal, P.R. Auxiliary Liver Transplantation for 

Toxic Mushroom Poisoning. J. Pediatr. 2001, 138 (3), 

449. 

121. Beaudreuil, S.; Sharobeem, R.; Maître, F.; Karsenti, D.; 

Crezard, O.; Pierre, D. Toxicité Rénale de L’amanite 




phalloïde. Une Observation avec Ponction Biopsie 

Rénale. Presse Méd. 1998, 27 (28), 1434. 

122. Cochran, K.W. 1998 Annual Report of the North 

American Mycological Association’s Mushroom Poisoning 

Case Registry. McIlvainea 1999, 14 (1), 93–98. 

123. Gimson, A.E.S.; Braude, S.; Mellon, P.J.; Canalese, J. 

Earlier Charcoal Haemoperfusion in Fulminant Hepatic 

Failure. Lancet 1982, 681–683. 

124. Horn, K.D.; Wax, P.; Schneider, S.M.; Martin, T.G.; 

Nine, J.S.; Moraca, M.A.; Virji, M.A.; Aronica, P.A.; 

Rao, K.N. Biomarkers of Liver Regeneration Allow 

Early Prediction of Hepatic Recovery After Acute 

Necrosis. Am. J. Clin. Pathol. 1999, 112, 351–357. 

125. Butera, R.; Locatelli, C.; Maccarini, D.; Candura, S.M.; 

Manzo, L. Emploi de la N-Acetylcystéine dans 

L’intoxication par Amanita phalloides: Résultats Cliniques. 

Résumés des Communications. XXXIème Congrès 

de la Société de Toxicologie Clinique, Nancy, 

France, Sept 16–17, 1993; 29. 

126. Dolfi, F.; Gonnella, R. Intossicazione Acuta da Amanita 

phalloide nel Secondo Trimestre di Gravidenza. Minerva 

Anestesiol. 1994, 60, 153–154. 

127. Hruby, K. Knollenblätterpilzvergiftung. Intensivmedizin 

1987, 24, 269–274. 

128. Hruby, K. Treatment of Death Cap Fungus with 

Silibinin. 10th Congress of the International Society 

for Human and Animal Mycology, Barcelona, Spain, 

Jun 1988; 361–363. 

129. Plackova, S.; Caganova, B. Acute Intoxications by 

Mushrooms and Plants in Slovakia. Clin. Toxicol. 1998, 

36, 452–453. 

130. Zilker, T.R.; Felgenhauer, N.J.; Michael, H.; Strange- 

Hesse, A. Grading of Severity and Therapy of 154 Cases 

of Amanita Poisoning. Vet. Hum. Toxicol. 1993, 35 (4), 

331. 

131. Russo, G.E.; Giusti, S.; Maurici, M.; Bosco, M.; 

Vitaliano, E.; Caramiello, M.S.; Bauco, B.; De Marco, 

C.M.; Marigliano, V. Plasmapheresi e Avvelenamento 

da Funghi: Presentazione di un Caso di Intossicazione da 

Amanita phalloides. Clin. Ter. 1997, 148 (5–6), 

277–280. 

132. Plotzker, R.; Jensen, D.M.; Payne, J.A. Case Report 

Amanita virosa Acute Hepatic Necrosis: Treatment 

with Thioctic Acid. Am. J. Med. Sci. 1982, 283 (2), 

79–81. 

133. Bektas, H.; Schlitt, H.J.; Böker, K.; Brunkhorst, R.; 

Oldhafer, K.J.; Pichlmayr, R. Indikationsstellung zur 

Lebertransplantation bei Schwerer Knollenblätterpilzvergiftung 

(Indication for Liver Transplantation in 

Severe Amanita phalloides Mushroom Poisoning). 

Chirurg 1996, 67, 996–1001. 

134. Pehlivanoglu, E.; Lawrence, R.A.; Canpolat, C. Treatment 

of Amanita phalloides Intoxication. A Report of 3 

Cases and Review of the Literature. Int. Pediatr. 1991, 6 

(4), 366–370.

135. Aji, D.Y.; Caliskan, S.; Nayir, A.; Mat, A.; Can, B.; 

Yasar, Z.; Ozsahin, H.; Cullu, F.; Sever, L. Haemoperfusion 

in Amanita phalloides Poisoning. J. Trop. Pediatr. 

1995, 41, 371–374. 

136. Favarel-Garrigues, J.C.; Saric, J.; Janvier, F.; Wickers, 

F.; Masson, B.; Winnock, S.; Couzigou, P.; Lugrin, D.; 

Penouil, F.; De Mascarel, A. Intoxication Phalloïdienne 

Grave—Transplantation Hépatique: Un Recours Possible 

(à Propos d’une Observation). Soc. Fr. Toxicol. 

1988, 8, 62. 

137. Rangé Grasland, L. Intoxication Volontaire par L’amanite 

phalloïde (à Propos d’un Cas). Thèse de Médecine, 

Université de Rennes 1: France, 1986, 96. 

138. Pescador Guiral, C. Intoxications Phalloïdiennes: À 

Propos de 29 Cas Recensés par le Centre Anti-Poisons 

de Toulouse Entre 1983 et 1994. Propositions Thérapeutiques. 

Thèse de Médecine, Université de Toulouse 

III: France, 1995, 179. 

139. Cappell, M.S.; Hassan, T. Gastrointestinal and Hepatic 

Effects of Amanita phalloides Ingestion. J. Clin. 

Gastroenterol. 1992, 15 (3), 225–228. 

140. Feinfeld, D.A.; Mofenson, H.C.; Caraccio, T.; Kee, M. 

Poisoning by Amatoxin-Containing Mushrooms in 

Suburban New York—Report of Four Cases. Clin. 

Toxicol. 1994, 32 (6), 715–721. 

141. Mullins, M.E.; Horowitz, B.Z. The Futility of Hemoperfusion 

and Hemodialysis in Amanita phalloides 

Poisoning. Vet. Hum. Toxicol. 2000, 42 (2), 90–91. 

142. Saltik, I.N.; Soysal, A.; Sarikayalar, F.; Topalgu, R.; 

Gurakan, F. Amanita Poisoning in a Child Treated with 

Plasma Exchange. Indian Pediatr. 2000, 37, 1028–1029. 

143. Locatelli, C.; Maccarini, D.; Ferruzi, M.; Olibet, G.; 

Ruggerone, M.L. Intossicazioni Acute da Amanita phalloides: 

Proposta di Terapia con N-Acetilcisteina. Ann. 

Mus. Civ. Rovereto 1989, 4 (1988, Suppl.), 211–212. 

144. Locatelli, C.; Travaglia, A.; Sala, G.; Maccarini, D.; 

Ruggerone, M.L. Ruolo Dell’ N-Acetilcisteinia e Della 

Diuresi Forzata nel Trattamento Dell’intossicazione 

Falloidea: Casistica Clinica. Minerva Anestesiol. 1990, 

56, 1361–1363. 

145. Locatelli, C.; Maccarini, D.; Travaglia, A.; Manzo, L. 

Prolonged High Dose N-Acetylcysteine Treatment of 

Amanita phalloides and Chlorinated Hydrocarbon 

Poisoning. Pharmacol. Res. 1992, 26, 201. 

146. Gayol, S.; Tournoud, C.; Flesch, F.; Berton, C.; 

Rusterholtz, T.; Raguin, O.; Liegeon, M.N.; Sauder, 

P.; Jaeger, A. Amatoxin Poisoning Due to Lepiota 

brunneoincarnata. Congrès Européen de Toxicologie, 

Marseille, France, Jun 4–7, 1966; 14. 

147. Pertile, N.; Galliani, E.; Vergerio, A.; Turrin, A.; Caddia, 

V. Sindrome Falloidea-Descrizione di un Caso in Una 

Bambina di due Anni. Ped. Med. Chr. (Med. Surg. Ped.) 

1990, 12, 411–414. 

148. Benvenuto, V. Intoxication Phalloïdienne: Aspects 

Botanique, Toxicologique, Clinique, Thérapeutique et 




Préventif. Thèse de Médecine, Université de Saint 

Etienne: France, 1989, 172. 

149. Sabeel, A.I.; Kurkus, J.; Lindholm, T. Intensive 

Hemodialysis and Hemoperfusion Treatment of Amanita 

Mushroom Poisoning. Mycopathologia 1995, 131, 

107–114. 

150. Daya, M.R.; Norton, R.L.; Fields, R.D.; Kao, R.; Lake, 

J.R.; Ascher, N.L.; Pinson, C.W.; Benner, K.G.; Keefe, 

E.B. Liver Transplantation in Amanita phalloides 

Poisoning. Vet. Hum. Toxicol. 1989, 31 (4), 360. 

151. Pinson, C.W.; Daya, M.R.; Benner, K.G.; Norton, R.L.; 

Deveney, K.E.; Ascher, N.L.; Roberts, J.P.; Lake, J.R.; 

Kurkchubasche, A.G.; Ragsdale, J.W.; Alexander, J.P.; 

Keefe, E.B. Liver Transplantation for Severe Amanita 

phalloides Mushroom Poisoning. Am. J. Surg. 1990, 

159, 493–499. 

152. Iivanainen, A.; Valtonen Ja Pertti, M.; Pentikäinen, J. 

Sienimyrkytys—Syksyn Sairaus (Mushroom Poisoning—A 

Disease of Autumn). Duodecim 1989, 105 (15), 

1313–1317. 

153. Madsen, S.; Jenssen, K.M. Forgiftning Med Hvit 

Fluesopp (Amanita virosa )—Symptomer, Diagnose og 

Behandling. Tidsskr. Nor. Laegeforen. 1990, 110 (14), 

1828–1829. 

154. Schiodt, F.V.; Ott, P.; Bondesen, S. Forgiftning Med 

Gron og Hvid Fluesvamp pä en Hepatologisk Specialafdeling, 

1989–1994 (Poisoning with Amanita phalloides 

and Amanita virosa Treated at a Department of 

Hepatology, 1989–1994). Ugeskr. Laeg. 1995, 157 (31), 

4350–4354. 

155. Nieter, B.; Frille, J. Plasmaaustausch bei Knollenblätterpilzvergiftung 

(Plasma Exchange in Amanita phalloides 

Mushroom Poisoning—A Case Report). Nieren-Hochdruckkr. 

1992, 21 (1), 8–10. 

156. Scheurlen, C.; Spannbrucker, N.; Spengler, U.; 

Zachoval, R.; Schulte-Witte, H.; Brensing, K.A. 

Amanita phalloides Intoxications in a Family of Russian 

Immigrants. Case Reports and Review of the Literature 

with a Focus on Orthotopic Liver Transplantation. 

Z. Gastroenterol. 1994, 32, 399–404. 

157. Rambousek, V.; Janda, J.; Sikut, M. Severe Amanita 

phalloides Poisoning in a 7-Year-Old Girl. Cesk. 

Pediatr. 1993, 48 (6), 332–333. 

158. Christen, Y.; Minazio, P.; de Moerloose, P. Monitoring 

of Haemostatic Parameters in Five Cases of Amanita 

phalloides Poisoning. Blood Coagul. Fibrinolysis 1993, 

4, 627–630. 

159. Serné, E.H.; Toorians, A.W.F.T.; Gietema, J.A.; 

Bronsveld, W.; Haagsma, E.B.; Mulder, P.O.M. 

Amanita phalloides, a Potentially Lethal Mushrooms: 

Its Clinical Presentation and Therapeutic Options. Neth. 

J. Med. 1996, 49 (1), 19–23. 

160. Jaros, F.; Kascak, M. Incidencia a Sucasna Liecba 

Cytotoxickych Cyclopeptidovych (Faloidnych) Otrav u 

Gravidnych Zien (Incidence and Contemporary Treat-

748 

ment of Cytotoxic Cyclopeptide (Phalloid) Intoxications 

in Pregnant Women). Vnitr. Lék. 1996, 42 (6), 414–417. 

161. Carducci, R.; Armellino, M.F.; Volpe, C.; Basile, G.; 

Caso, N.; Apicella, A.; Basile, V. Silibinina e 

Intossicazione Acuta da Amanita phalloides. Minerva 

Anestesiol. 1996, 62 (5), 187–193. 

162. Alves, A.; Ferreira, M.G.; Paulo, J.; França, A.; 

Carvalho, A. Mushroom Poisoning with Amanita 

phalloides. Eur. J. Int. Med. 2001, 12, 64–66. 

163. Marugg, D.; Reutter, F.W. Die Amanita phalloides- 

Intoxication Moderne Therapeutische Massnahmen und 

Klinischer Verlauf (Amanita phalloides Poisoning— 

Modern Therapeutic Procedures and Clinical Course). 

Schweiz. Rundsch. Med./Prax. 1985, 74 (37), 972–982. 

164. Hofer, J.F.; Egermann, G.; Mach, K.; Sommer, K. 

Therapie der Knollenblät-Terpilzergiftung mit Silibinin 

in Kombination mit Penicillin und Cortison. Wien. Klin. 

Wochenschr. 1983, 95 (7), 240–243. 

165. Hallas, J.; Jensen, K. Forgiftning Med Gron Fluesvamp. 

Ugeskr. Laeg. 1988, 150 (16), 975–978. 

166. Molling, J.; Pohle, W.; Klein, H.; Welte, T. Stellenwert 

Therapeutischer Maßnahmen bei Vergiftung mit dem 

Grünen Knollenblätterpilz (The Different Stages in the 

Treatment of Amanita phalloides Poisoning). Intensivmedizin 

1995, 32 (1), 37–42. 

167. Homann, J.; Rawer, P.; Bleyl, H.; Matthes, K.J.; 

Heinrich, D. Early Detection of Amatoxins in Human 

Mushroom Poisoning. Arch. Toxicol. 1986, 59, 

190–191. 

168. Bourgeois, F.; Bourgeois, N.; Gelin, M.; Van de Stadt, 

J.; Doutrelepont, J.M.; Adler, M. Hépatite Aiguë et 

Intoxication à L’amanite Phalloïde. Acta Gastroenterol. 

Belg. 1992, LV, 358–363. 

169. Soyez, C.; Autret, E.; Laugier, J.; Broué P.; Crèche, 

J. Intoxication Familiale par Lepiota helveola. Résumés 

des Communications. XXXIème Congrès de la Société 

de Toxicologie Clinique, Nancy, France, Sept 16–17, 

1993; 28. 

170. Jankowska, I.; Malenta, G.; Rysko, J.; Socha, J.; 

Wozniewicz, M. Analiza Kliniczno–Morfologiczna 

Dzieci Zmarlych z Powodu Zatrucia Muchomorem 

Sromotnikowym (The Clinical–Morphological Analysis 

of Children Dying of Intoxication with Amanita 

phalloides ). Wiad. Lék. 1992, XLV, 21–22. 

171. Ryzko, J.; Jankowska, I.; Socha, J. Ostra Nierwydolnosci 

Watroby po Zatruciu Muchomorem Sromotnikowym 

(Acute Hepatic Liver Failure After Poisoning with 

Amanita phalloides). Wiad. Lék. 1987, 40 (21), 

1453–1458. 

172. Socha, J. Mushroom Poisoning in Children. 10th 

International Congress of the Society for Human and 

Animal Mycology, Barcelona, Spain, June, 1988; 

356–360. 

173. Pach, J.; Zajac, J.J.; Chrostek-Maj, J.; Wiernikowski, A. 

Porownanie Skutecznosci Rosnych Modeli Postepowa- 




nia Leczniczego w Ostrym Zatruciu Muchomorem 

Sromotnikowym (Comparison of the Effectiveness of 

Various Models of Therapeutic Man Amanita Poisoning). 

Pol. Tyg. Lék. 1987, XLII (11), 322–324. 

174. Ponikvar, R.; Drinovec, J.; Kandus, A.; Varl, J.; Gucek, 

A.; Malovrh, M. Plasma Exchange in Management of 

Severe Acute Poisoning with Amanita phalloides. Apher 

1990, 327–329. 

175. Jankowska, I.; Grenda, R.; Rysko, J.; Litwin, M.; 

Prokurat, S.; Rychlik, G.; Smirska, E.; Kaliszan, A.; 

Socha, J. Ocena Przydatnosci Plazmaferezy w Leczeniu 

Zatruc Muchomorem Sromotnikowym (Evaluation de la 

Plasmaphérèse dans le Traitement de l’intoxication par 

Amanita phalloides ). Pol. Tyg. Lék. 1993, XLVII 

(18–19), 427–429. 

176. Bartoloni St Omer, F.; Giannini, A.; Botti, P.; Caramelli, 

L.; Ledda, F.; Peruzzi, S.; Zorn, M. Amanita Poisoning: 

A Clinical–Histopathological Study of 64 Cases of 

Intoxication. Hepatogastroenterology 1985, 32, 

229–231. 

177. Fantozzi, R.; Ledda, F.; Caramelli, L.; Moroni, F.; 

Blandina, P.; Masini, E.; Botti, P.; Peruzzi, S.; Zorn, M.; 

Mannaioni, P.F. Clinical Findings and Follow-Up 

Evaluation of an Outbreak of Mushroom Poisoning— 

Survey of Amanita phalloides Poisoning. Klin. 

Wochenschr. 1986, 64, 38–43. 

178. Piering, W.F.; Bratanow, N. Role of the Clinical 

Laboratory in Guiding Treatment of Amanita virosa 

Mushroom Poisoning: Report of Two Cases. Clin. 

Chem. 1990, 36 (3), 571–574. 

179. Iliev, Y.; Andonova, S.; Akabaliev, V. Our Experience 

in the Treatment of Acute Amanita phalloides Poisoning. 

Folia Med. 1999, XLI (4), 30–37. 

180. Mydlik, M.; Derzsiova, K.; Mizla, P.; Beno, P. Pouzitie 

Hemoperfuzie pri Otrave Hubami. Klinicky Rozbor 58 

Chorych (Use of Haemoperfusion in Mushroom 

Poisoning. Clinical Analysis of 58 Patients). Cas. Lék. 

Cesk. 1993, 132 (15), 464–466. 

181. Buffoni, L.; Chiossi, M.; De Santis, L.; Galletti, A.; 

Lattere, M.; Pesce, F.; Reboa, E.; Renna, S.; Rosati, U.; 

Tarateta, A.; Tasso, L. l’Avvelenamento nell’Infanzia da 

Amanita velenosa “Mortale”. Minerva Pediatr. 1986, 38, 


182. Sanz, P.; Reig, R.; Borras, L.; Martinez, J.; Manez, R.; 

Corbella, J. Disseminated Intravascular Coagulation and 

Mesenteric Venous Thrombosis in Fatal Amanita 

Poisoning. Hum. Toxicol. 1988, 7, 199–201. 

183. Sanz, P.; Reig, R.; Piqueras, J.; Marti, G.; Corbella, J. 

Fatal Mushroom Poisoning in Barcelona, 1986–1988. 

Mycopathologia 1989, 108, 207–209. 

184. Sese Torres, J.; Piqueras Carrasco, J.; Morlans Molina, 

G. Intoxicacion por Amanita phalloides: Diagnostico 

por Radioinmunoanalisis y Tratamiento con Diuresis 

Forzada (Poisoning with Amanita phalloides. 

Diagnosis by Radioimmunoassay and Treatment

with Forced Diuresis). Med. Clin. 1985, 84 (16), 

660–662. 

185. Vesconi, S.; Langer, M.; Iapichino, G.; Constantino, D.; 

Busi, C.; Fiume, L. Therapy of Cytotoxic Mushroom 

Intoxication. Crit. Care Med. 1985, 13, 402–406. 

186. Capellaro, L.; Lupo, F.; Tiboldo, F.; Belotti, M.T.; 

Spagarino, E. Esperienza Riguardo All’uso Della 

Plasmaferesi in Patologie di Interesse Rianimatorio. 

Minerva Med. 1987, 78, 1565–1570. 

187. Lopez, A.; Jerez, V.; Rebollo, J.; Lombardo, A.G.; Julia, 

J.A. Fulminant Hepatitis and Liver Transplantation. 

Ann. Intern. Med. 1988, 108, 769. 

188. Ramirez, P.; Parrilla, P.; Bueno, F.S.; Robles, R.; Pons, 

J.A.; Bixquert, V.; Nicolas, S.; Nunez, R.; Alegria, M.S.; 

Miras, M.; Rodriguez, J.M. Fulminant Hepatic Failure 

After Lepiota Mushroom Poisoning. J. Hematol. 1993, 

19, 51–54. 

189. Castiella, A.; Lopez Dominguez, L.; Txoperena, G.; 

Cosme, A.; Aramburu, V.; Arenas, J.I. Indication de la 

Transplantation du Foie en Cas d’Intoxication par 

Amanite Phalloïde. Presse Méd. 1993, 22 (4), 177. 

190. Van Cauter, J.; Quarre, J.P.; Demay, M.; Pollart, C.; 

Ligny, C. Intoxication Familiale par Amanite Phalloïde. 

Acta Gastroenterol. Belg. 1984, XLVII, 47–54. 

191. Boyer, J.C.; Hernandez, F.; Estorc, J.; De La Coussaye, 

J.E.; Bali, J.P. Management of Maternal Amanita 

phalloides Poisoning During the First Trimester of 

Pregnancy: A Case Report and Review of the Literature. 

Clin. Chem. 2001, 47 (5), 971–974. 

192. Perrier, A.L. Syndrome Phalloïdien: à Propos d’une 

Intoxication chez la Femme Enceinte à Treize Semaines 

d’Aménorrhée. Thèse de Médecine, Université Montpellier 

I: France, 1998, 116. 

193. Woodle, E.S.; Moody, R.R.; Cox, K.L.; Cannon, R.A.; 

Ward, R.E. Orthotopic Liver Transplantation in a Patient 

with Amanita Poisoning. J. Am. Med. Assoc. 1985, 253 

(1), 69–70. 

194. Dumont, A.M.; Chennebault, J.M.; Alquier, P.; Jardel, 

H. Management of Amanita phalloides Poisoning by 

Bastien’s Regimen. Lancet 1981, 1, 722. 

195. Boiffard, J. Une Intoxication Familiale par Lepiota 

brunneolilacea. Doc. Mycol. 1987, XVIII (69), 21–23. 

196. Daoudal, P.; Noirot, A.; Wagschal, G.; Neftel, K.; Hany, 

M.; Clément, D.; Floriot, C.; Delacour, J.L. Traitement 

de l’intoxication Phalloïdienne par Silymarine et 

Ceftazidime. Presse Méd. 1989, 18 (27), 1341–1342. 

197. Heurtebize, P. Intoxication Phalloïdienne: À Propos de 

Cinq Cas Traités par Ceftazidime et Silymarine. Thèse 

de Médecine, Université de Besançon: France, 1990, 192. 

198. Meunier, B.; Messner, M.; Bardaxoglou, E.; Spiliopoulos, 

G.; Terblanche, J.; Launois, B. Liver Transplantation 

for Severe Lepiota helveola Poisoning. Liver 

1994, 14, 158–160. 

199. Galler, G.W.; Weisenberg, E.; Brasitus, T.A. Mushroom 

Poisoning: The Role of Orthotopic Liver 




Transplantation. J. Clin. Gastroenterol. 1992, 15 (3), 

229–232. 

200. Haines, J.H.; Lichstein, E.; Glickerman, D. A Fatal 

Poisoning from an Amatoxin Containing Lepiota. 

Mycopathologia 1985, 93, 15–17. 

201. Jander, S.; Bischoff, J. Treatment of Amanita phalloides 

Poisoning: I. Retrospective Evaluation of Plasmapheresis 

in 21 Patients. Ther. Apher. 2000, 4 (4), 303–307. 

202. Olesen, L.L. Amatoxin Intoxication. Scand. J. Urol. 

Nephrol. 1990, 24, 231–234. 

203. Nagy, I.; Pogatsa-Murray, G.; Zalanyi, S.; Komlosi, P.; 

Laszlo, F.; Ungi, I. Amanita Poisoning During the Second 

Trimester of Pregnancy. A Case Report and a Review of 

the Literature. Clin. Investig. 1994, 72, 794–798. 

204. Mikos, B.; Biro, E. Amanita phalloides Poisoning in a 

15-Year Case Load of a Pediatric Intensive Care Unit. 

Orv. Hetil. 1993, 134 (17), 907–910. 

205. Trestail, J.H. Mushroom Poisoning Case Registry: North 


McIlvainea 1993, 11 (1), 51–60. 

206. Trestail, J.H. Mushroom Poisoning Case Registry: 


207. Trestail, J.H. 1997 Annual Report of the North American 

Mycological Association’s Mushroom Poisoning Case 

Registry. McIlvainea 1998, 13 (2), 86–92. 

208. Trestail, J.H. Mushroom Poisoning Case Registry: North 


McIlvainea 1994, 11 (2), 87–95. 

209. Trestail, J.H. Mushroom Poisoning Case Registry: North 

American Mycological Association Report 1989–90. 

McIlvainea 1991, 10 (1), 36–44. 

210. Dimitrov, C.; Nikova, M. Intensive Care Treatment in 

Patients on Acute Haemodialysis/Haemoperfusion. 

XXXth Congress of EDTA, Vienna, Austria, 1994; 77. 

211. Hubenova, A.; Stankova, E. Some Recent Problems in 

Amanita phalloides Poisonings. Congress of Anti- 

Poisons Centre, Istambul, Turkey, May 24–27, 1992; 

37. 

212. De Haro, L.; Jouglard, J.; Hayek, M.; David, J.M.; 

Arditti, J.; Bourdon, J.H.; Blanchard, M.; Regli, P.; 

Bechtel, Y.; Bechtel, P. Un Cas d’Intoxication par 

Amanites Printanières: Étude de l’Atteinte Hépatique. 

XXXIème Congrès de la Société de Toxicologie 

Clinique, Nancy, France, Sept 16–17, 1993; 27. 

213. Timar, L.; Czeizel, A.E. Birth Weight and Congenital 

Anomalies Following Poisonous Mushroom Intoxication 

During Pregnancy. Reprod. Toxicol. 1997, 11 

(6), 861–866. 

214. Misiuk-Hojio, M.; Magnowska-Wozniak, M. Powiklania 

Oczne w Zatruciu Muchomorem Sromotnikowym 

(Ocular Complications in Amanita phalloides Poisoning). 

Klin. Oczna 1996, 98 (1), 59–60. 

215. Mydlik, M.; Mizla, P.; Derzsiova, K.; Beno, P.; 

Matheova, E. Extracorporeal Treatment of Acute 

Renal Failure (ARF) and Acute Poisoning (AP) in

750 

Children and Adolescents—27 Year Experiences. 

XXXth Congress of EDTA, Vienna, Austria, 1994; 82. 

216. Brunelli, F. Première Suisse à Genève: Un Enfant de 7 

ans, Intoxiqué par Amanita phalloides, est Sauvé par une 

Greffe de Foie. Schweiz. Z. Pilzkd. 1992, 70 (4), 85–86. 

217. Römer, E. Rapport du Toxicologue de l’USSM pour 

1987. Schweiz. Z. Pilzkd. 1988, 66 (11), 202–203. 

218. Anonymous. From the Centers for Disease Control and 

Prevention; Amanita phalloides Mushroom Poisoning— 

Northern California, January 1997. J. Am. Med. Assoc. 

1997, 278 (1), 16–17. 

219. Nordt, S.P.; Manoguerra, A.; Clark, R.F. 5-Year 

Analysis of Mushroom Exposures in California. West. 

J. Med. 2000, 173 (5), 314–317. 

220. Jaeger, A.; Flesch, F.; Jehl, F.; Sauder, P.; Kopferschmitt, 

J. Les Intoxications par Champignons. J. Méd. 

Strasb. 1988, 19 (7), 381–384. 

221. Forgittoni, R.; Vecchiarelli, P.; Lepri, F.; Casagrande, 

G.C.; Quadrani, G.; Meletti, M. Le Intossicazioni 

Esogene Acute Presso il Centro di Rianimazione 

dell’Ospedale di Viterbo nel Decennio 1-10-1979/31- 

12-1989 (Acute Poisoning Cases in the Intensive Care 

Unit of the “Ospedale Grande” in Viterbo from 1-X-79 

to 31-XII-89). Acta Anaesthesiol. Ital. 1992, 43, 79–93. 

222. Pinson, C.W.; Bradley, A.L. A Primer for Clinicians on 

Mushroom Poisoning in the West. West. J. Med. 1996, 

165, 318–319. 

223. Anonymous. Consensus Thérapeutique Face à l’Intoxication 

Phalloïdienne. In Centre Anti-Poisons de Toulouse;Hôpitaux 

de Toulouse: Toulouse, France, 1995; 7. 

224. Parish, R.C.; Doering, P.L. Treatment of Amanita 

Poisoning: A Review. Vet. Hum. Toxicol. 1986, 28 (4), 

318–322. 

225. Köppel, C. Clinical Symptomatology and Management 

of Mushroom Poisoning. Toxicon 1993, 31 (12), 

1513–1540. 

226. Barriot, P.; Masson, B.; Fournier, S. Intoxications par les 

Champignons. Rev. Prat. 2000, 50, 396–400. 

227. Basak, M.; Cosansel, S.; Ozer, A.; Bilgi, O.; Danaci, M. 

Mantar Zehirlenmeleri ve Tedavisi (Mushroom Poisonings 

and Their Treatment). Sendrom 1998, 10 (9), 


228. Stetkova, A. Errors of Diagnostics and Therapy of 

Poisoning with Amanita phalloides. Ceska Mykol. 1991, 

45, 47. 

229. American Academy of Clinical Toxicology; European 

Association of Poisons Centres and Clinical Toxicologists; 

Position Statement: Ipecac Syrup. Clin. Toxicol. 

1997, 35 (7), 699–709. 

230. American Academy of Clinical Toxicology; European 

Association of Poisons Centres and Clinical Toxicologists. 

Position Statement: Gastric Lavage. Clin. Toxicol. 

1997, 35 (7), 711–719. 

231. Anonymous. Poisindex w and Identidex w Toxicology 

Information; Micromedex Health Care Series; Micro- 




medex Inc. Intranet Knowledge Bases 1974–1999; Vol. 

99, Expires 3/99. 



Position Statement: Whole Bowel Irrigation. Clin. 

Toxicol. 1997, 35 (7), 753–762. 

233. Rabe, C.; Scheurlen, C.; Caselmann, W.H. Vorgehen bei 

Knollenblätterpilzergiftung. Dtsch. Med. Wochenschr. 

1999, 124, 1073–1076. 



Position Statement: Cathartics. Clin. Toxicol. 

1997, 35 (7), 743–752. 

235. Ryzko, J.; Jankowska, I.; Socha, J. Ocena Wybranych 

Parametrow Gospodarki Wapniowo-Iosioranowej w 

Ostrej Nierwydolnosci Watroby po Zatruciu Muchomorem 

Sromotnikowym (Selected Parameters of Calcium 

and Phosphate Metabolism in the Acute Liver 

Failure Following Poisoning with Amanita phalloides ). 

Pol. Tyg. Lék. 1990, XLV (49–50), 990–992. 

236. Parra, S.; Garcia, J.; Martinez, P.; De La Pena, C.; 

Carrascosa, C. Profile of Alkaline Phosphatase Isoenzymes 

in Ten Patients Poisoned by Mushrooms of the 

Genus Lepiota. Dig. Dis. Sci. 1992, 37 (10), 

1495–1498. 

237. Faulstich, H.; Zobeley, S.; Trischmann, H. A Rapid 

Radioimmunoassay, Using a Nylon Support, for 

Amatoxins from Amanita Mushrooms. Toxicon 1982, 

20 (5), 913–924. 

238. Frei, W.; Andres, R.; Gautschi, K.; Vonderschmitt, D. 

Eine Neue Methode zur Raschen Bestimmung von 

Knollenblätterpilzgift im Urin und im Plasma (A New 

Method for the Rapid Detection of Amanita Toxins in 

the Urine and Plasma). Schweiz. Med. Wochenschr. 

1986, 116 (26), 892–893. 

239. Dorizzi, R.; Michelot, D.; Tagliaro, F.; Ghielmi, S. 

Methods for Chromatographic Determination of Amanitins 

and Related Toxins in Biological Samples. 

J. Chromatogr. (Biomed. Appl.) 1992, 580, 279–291. 

240. Defendenti, C.; Bonacina, E.; Mauroni, M.; Gelosa, L. 

Validation of a High Performance Liquid Chromatographic 

Method for Alpha Amanitin Determination in 

Urine. Forensic Sci. Int. 1998, 92, 59–68. 

241. Brüggemann, O.; Meder, M.; Freitag, R. Analysis of 

Amatoxins a-Amanitin and b-Amanitin in Toadstool 

Extracts and Body Fluids by Capillary Zone Electrophoresis 

with Photodiode Array Detection. 

J. Chromatogr. A 1996, 744, 167–176. 

242. Fartushnyi, A.F.; Sukhin, A.P.; Fartushnaya, Y.A. 

Chemical and Toxicological Studies in Mushroom 

Poisonings. Sud. Med. Ekspert. 2000, 43 (2), 21–24. 

243. Jankowska, I.; Rysko, J.; Kuryl, T.; Socha, J. 

Przydatnosc Oznaczania Amanityny Metoda RIA w 

Diagnostyce Zatruc Muchomorem Sromotnikowym u 

Dzieci (Value of Amanitin Determination with RIA

Technique for the Diagnosis of Poisoning with Amanita 

phalloides in Childhood). Pol. Tyg. Lék. 1988, XLIII, 

585–588. 

244. Mas, A.; Rodés, J. Fulminant Hepatic Failure. Lancet 

1997, 349, 1081–1085. 

245. Gill, R.Q.; Sterling, R.K. Acute Liver Failure. J. Clin. 

Gastroenterol. 2001, 33 (3), 191–198. 

246. Vesconi, S.; Langer, M.; Costantino, D.; Iapichino, G.; 

Macchi, R. Clinical Evaluation of Amatoxin Removal 

Approach in Amanita phalloides Poisoning. In Amanita 

Toxins and Poisonings; Faulstich, H., Kommerell, B., 

Wieland, T., Eds.; Lubrecht Cramer: New York, 1980; 

232–236. 



Position Statement: Single-Dose Activated Charcoal. 

Clin. Toxicol. 1997, 35 (7), 721–741. 

248. Faulstich, H.; Talas, A.; Wellhöner, H.H. Toxicokinetics 

of Labeled Amatoxins in the Dog. Arch. Toxicol. 1985, 

56, 190–194. 

249. Faulstich, H. New Aspects of Amanita Poisoning. Klin. 

Wochenschr. 1979, 57, 1143–1152. 

250. Floersheim, G.L. Treatment of Human Amatoxin 

Mushroom Poisoning. Myths and Advances in Therapy. 

Med. Toxicol. 1987, 2, 1–9. 

251. Buchwald, A. Amanita Poisoning. Am. J. Med. 1989, 87, 

702. 

252. Busi, C.; Fiume, L.; Costantino, D.; Langer, M.; 

Vesconi, F. Amanita Toxins in Gastroduodenal Fluid 

of Patients Poisoned by the Mushroom, Amanita 

phalloides. N. Engl. J. Med. 1979, 300, 800. 

253. Langer, M.; Vesconi, S.; Costantino, D.; Busi, C. 

Pharmacodynamics of Amatoxins in Human Poisoning 

as the Basis for the Removal Treatment. In Amanita 



90–97. 

254. Vesconi, S.; Langer, M.; Costantino, D. Mushroom 

Poisoning and Forced Diuresis. Lancet 1980, 854–855. 

255. Piqueras, J.; Duran-Suarez, J.R.; Massuet, L.; Hernandez-Sanchez, 

J.M. Mushroom Poisoning: Therapeutic 

Aphereris or Forced Diuresis. Transfusion 1987, 27 (1), 

116–117. 

256. Jaeger, A.; Jehl, F.; Flesch, F.; Sauder, P.; Kopferschmitt, 

J.; Minck, R.; Mantz, J.M. Cinétique de l’amanitine 

au Cours des Intoxications Phalloïdiennes. Réanim. 

Soins Intens. Méd. Urgence 1985, 1, 262. 

257. Jaeger, A.; Jehl, F.; Flesch, F.; Sauder, P.; Kopferschmitt, 

J. Kinetics of Amatoxins in Human Poisoning: Therapeutic 

Implications. Clin. Toxicol. 1993, 31, 63–80. 

258. Busi, C.; Fiume, L.; Costantino, D.; Borroni, M.; 

Ambrosino, G.; Olivotto, A.; Bernardini, D. Détermination 

des Amanitines dans le Sérum de Patients 

Intoxiqués par l’Amanite Phalloïde. Nouv. Presse Méd. 

1977, 6 (32), 2855–2857. 




259. Wauters, J.P.; Rossel, C.; Farquet, J.J. Amanita 

phalloides Poisoning Treated by Early Charcoal 

Haemoperfusion. Br. Med. J. 1978, 2, 1465. 

260. Bartels, O.; Topf, G. Amanita phalloides Poisoning— 

Indication for Early Haemoperfusion. In Amanita Toxins 

and Poisonings; Faulstich, H., Kommerell, B., Wieland, 

T., Eds.; Lubrecht Cramer: New York, 1980; 147–154. 

261. Czygan, P.; Zimmermann, R.; Leuschner, U.; Stiehl, 

A.; Kommerell, B. Clinical, Biochemical and 

Morphological Alterations in Patients with Amanita 

phalloides Intoxication. In Amanita Toxins and 

Poisonings; Faulstich, H., Kommerell, B., Wieland, 

T., Eds.; Lubrecht Cramer: New York, 1980; 

131–136. 

262. Balsam, L.; Coritsidis, G.N.; Feinfeld, D.A. Role of 

Hemodialysis and Hemoperfusion in the Treatment of 

Intoxications. Crit. Care Toxicol. 1991, 1 (3), 61–79. 

263. Lambert, H.; Laprévote-Heully, M.C.; Manel, J.; 

Claude, D.; Delorme, N.; Larcan, A. Bilan de 

l’Utilisation de l’Hémoperfusion dans le Traitement 

des Intoxications Aiguës. A Propos de 23 Observations. 

Ann. Méd. Nancy Est 1981, 20, 935–946. 

264. Czygan, P.; Stiehl, A.; Kommerell, B. Treatment of 

Acute Amanita phalloides Induced Hepatic Failure by 

Haemoperfusion. In Amanita Toxins and Poisonings; 

Faulstich, H., Kommerell, B., Wieland, T., Eds.; 

Lubrecht Cramer: New York, 1980; 155–161. 

265. Lambert, H. Pronostic et Traitement de l’Intoxication. In 

Réanimation des Intoxications Aiguës; Baud, F., Ed.; 

Masson: Paris, France, 1995; 185–195. 

266. Langescheid, C.; Schmitz-Salue, H.; Faulstich, H.; 

Kramer, P.; Scheler, F. In Vitro Elimination of 

( 3 H)Methyl-dehydroxymethyl-a-Amanitin by Four 

Different Extracorporeal Detoxification Methods. In 

Amanita Toxins and Poisonings; Faulstich, H., Kommerell, 

B., Wieland, T., Eds.; Lubrecht Cramer: New 

York, 1980; 137–146. 

267. Monhart, V.; Balikova, M.; Tlustakova, M. Sorpcni 

Ucinnost Ceskych Hemoperfuznich Sorbentu pro 

Amatoxiny (Sorption Effectiveness of Czech Haemoperfusion 

Sorbents for Amatoxins). Cas. Lék. Cesk. 

1994, 6, 181–183. 

268. Mydlik, M.; Derzsiova, K.; Klan, J.; Zima, T. 

Hemoperfusion with a-Amanitin: An In Vitro Study. 

Int. J. Artif. Organs 1997, 20 (2), 105–107. 

269. Monhart, V. Otravy Muchomurkami a Vyznam Sorpcni 

Hemoperfuze pri Jejich Léceni (Toadstool Intoxications 

and Importance of Sorption Haemoperfusion in Their 

Treatment). Vnitr. Lék. 1997, 43 (10), 686–690. 

270. Mercuriali, F.; Sirchia, G. Plasma Exchange for 

Mushroom Poisoning. Transfusion 1977, 17, 644. 

271. Ariani, G.; Ciccarelli, P.; Ghergo, G.F.; Reverberi, R. 

Qualche Considerazione sul Trattamento Terapeutico di 

Tre Casi di Avvelenamento Acuto da Amanita Falloide 

(Remarks on the Therapy of the Three Cases of Acute

752 

Amanita phalloides Poisoning). Minerva Anestesiol. 

1979, 45, 335–344. 

272. Pigrau, C.; Martinez-Vazquez, M.; Piqueras, J. Intoxicacion 

por Amanita phalloides. Med. Clin. 1984, 83, 

342–345. 

273. Jander, S.; Bischoff, J.; Woodcock, B.G. Plasmapheresis 

in the Treatment of Amanita phalloides Poisoning. II. A 

Review and Recommendations. Ther. Apher. 2000, 4 

(4), 308–312. 

274. Floersheim, G.L.; Schneeberger, J.; Bucher, K. Curative 

Potencies of Penicillin in Experimental Amanita 

phalloides Poisoning. Agents Actions 1971, 2 (3), 

138–141. 

275. Floersheim, G.L. Antagonistic Effects of Phalloidin a- 

Amanitin and Extracts of Amanita phalloides. Agents 

Actions 1971, 2 (3), 142–149. 

276. Floersheim, G.L.; Eberhard, M.; Tschumi, P.; Duckert, 

F. Effects of Penicillin and Silymarin on Liver Enzymes 

and Blood Clotting Factors in Dogs Given a Boiled 

Preparation of Amanita phalloides. Toxicol. Appl. 

Pharmacol. 1978, 46, 455–462. 

277. Jahn, W.; Faulstich, H.; Wieland, T. Pharmacokinetics 

of ( 3 H)Methyldehydroxymethyl-a-amanitin in the Isolated 

Perfused Rat Liver and the Influence of Several 

Drugs. In Amanita Toxins and Poisonings; Faulstich, H., 

Kommerell, B., Wieland, T., Eds.; Lubrecht Cramer: 

New York, 1980; 79–87. 

278. Tamai, I.; Terasaki, T.; Tsuji, A. Evidence for the 

Existence of a Common Transport System of b-Lactam 

Antibiotics in Isolated Rat Hepatocytes. J. Antibiot. 

1985, 38 (12), 1774–1780. 

279. Kröncke, K.D.; Fricker, G.; Meier, P.; Gerock, W.; 

Wieland, T.; Kurz, G. a-Amanitin Uptake into 

Hepatocytes: Identification of Hepatic Membrane 

Transport Systems Used by Amatoxins. J. Biol. Chem. 

1986, 261 (27), 12562–12567. 

280. Floersheim, G.L. Toxins and Intoxications from the 

Toadstool Amanita phalloides. Trends Pharmacol. Sci. 

1983, 4, 263–266. 

281. Fiume, L.; Serti, S.; Montanaro, L.; Busi, C.; Costantino, 

D. Amanitins Do Not Bind to Serum Albumin. Lancet 

1977, 1, 1111. 

282. Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary 

System, 10th Ed.; Blackwell Science Ltd.: Oxford, UK, 

1997; 87–102, 651–672. 

283. Cottagnoud, P.; Neftel, K.A. b-Lactams Act on DNA 

Synthesis in K-562 Cells. Cell Biol. Toxicol. 1986, 2, 


284. Hübscher, U.; Do Huynh, U.; Hässig, M.; Neftel, K.A. 

Effects of b-Lactams on DNA Replication. Cell Biol. 

Toxicol. 1986, 2 (4), 541–547. 

285. Neftel, K.A.; Hübscher, U. Effects of b-Lactam 

Antibiotics on Proliferating Eucaryotic Cells. 

Antimicrob. Agents Chemother. 1987, 31 (11), 

1657–1661. 




286. Neftel, K.A.; Keusch, G.; Cottagnoud, P.; Widmer, U.; 

Hany, M.; Gautschi, K.; Joos, B.; Walt, H. Sind 

Cephalosporine bei der Intoxikation mit Knollenblätterpilz 

Besser Wirksam als Penicillin-G? Schweiz. Med. 

Wochenschr. 1988, 118 (2), 49–51. 

287. DeSwarte, R.D. Drug–Allergy Problems and Strategies. 

J. Allergy Clin. Immunol. 1984, 74 (3), 209–221. 

288. Erffmeyer, J.E. Adverse Reactions to Penicillin. Ann. 

Allergy 1981, 47, 288–300. 

289. Al-Ramahi, M.; Leader, A.; Léveillé, M.C. An Allergic 

Reaction Following Intrauterine Insemination. Hum. 

Reprod. 1998, 13 (12), 3368–3370. 

290. Hruby, K.; Csomos, G.; Furhmann, M.; Thaler, H. 

Chemotherapy of Amanita phalloides Poisoning with 

Intravenous Silibinin. Hum. Toxicol. 1983, 2, 183–195. 

291. Hruby, K.; Fuhrmann, M.; Csomos, G.; Thaler, H. 

Pharmakotherapie der Knollenblätterpilzvergiftung mit 

Silibinin (Treatment with Silibinin for Amanita phalloides 

Poisoning). Wien. Klin. Wochenschr. 1983, 95 

(7), 225–231. 

292. Neftel, K.A.; Mueller, M.R.; Waelti, M.; Erni, J.; 

Gugler, M.; Arrenbrecht, S. Penicilin G Degradation 

Products Inhibit In Vitro Granulopoiesis. Br. 

J. Haematol. 1983, 54 (2), 255–260. 

293. Neftel, K.A.; Hauser, S.P.; Mueller, M. Inhibition of 

Granulopoiesis In Vivo and In Vitro by b-Lactam 

Antibiotics. J. Infect. Dis. 1985, 152 (1), 90–98. 

294. Neftel, K.; Mueller, M.R.; Widmer, U.; Huegin, A.W. b- 

Lactam Antibiotics Inhibit In Vitro Granulopoiesis and 

Proliferation of Some Other Cell Types. Cell Biol. 

Toxicol. 1986, 2 (4), 513–521. 

295. Neftel, K.A.; Waelti, M.; Schulthess, H.K.; Gubler, J. 

Adverse Reactions Following Intravenous Penicillin G 

Relate to Degradation of the Drug In Vitro. Klin. 

Wochenschr. 1984, 62 (1), 25–29. 

296. Smith, H.; Lerner, P.I.; Weinsten, L. Neurotoxicity and 

“Massive” Intravenous Therapy with Penicillin. Arch. 

Intern. Med. 1967, 120, 47–53. 

297. Moroni, F.; Fantozi, R.; Masini, E.; Mannaioni, P.F. A 

Trend in the Therapy of Amanita phalloides Poisoning. 

Arch. Toxicol. 1976, 36, 111–115. 

298. Floersheim, G.L.; Weber, O.; Tschumi, P.; Ulbrich, M. 

Die Klinische Knollenbblätter-Pilzvergiftung (Amanita 

phalloides ): Prognostische Faktoren und Therapeutische 

Massnahmen (Clinical Poisoning with Amanita phalloides 

(Death Cap): Prognostic Factors and Therapeutic 

Measures). Schweiz. Med. Wochenschr. 1982, 112 (34), 

1164–1177. 

299. Wagner, V.H.; Diesel, P.; Seitz, M. Zur Chemie und 

Analytik von Silymarin, aus Silybum marianum Gaertn. 

Arzneim.-Forsch. 1974, 24, 466–471. 

300. Halbach, G.; Trost, W. Zur Chemie und Pharmakologie 

des Silymarins Untersuchungen an Einigen Umsetzungsprodukten 

des Silybins. Arzneim.-Forsch. 1974, 24, 

866–868.

301. Anonymous. In The Index Merck. An Encyclopedia of 

Chemicals, Drugs, and Biologicals; Budavari, S., Ed.; 

Merck and Co., Inc.: Whitehouse Station, NJ, 1996; 

139–140, 1464. 

302. Hahn, V.G.; Lehmann, H.D.; Kürten, M.; Uebel, H.; 

Vogel, G.; Baumann, I.; Dobberstein, I.; Eisen, E.; 

Ersfeld, A.; Krüger, S.; Meier, E.; Walther, H. Zur 

Pharmakologie und Toxikologie von Silymarin, des 

Antihepatotoxischen Wirkprinzipes aus Silybum marianum 

(L.) Gaertn. Arzneim.-Forsch. 1968, 18, 

698–704. 

303. Vogel, V.G.; Trost, W.; Braatz, R.; Odenthal, K.P.; 

Brüsewitz, G.; Antweiler, H.; Seeger, R. Untersuchungen 

zu Pharmakodynamik, Angriffspunkt und Wirkungsmecha-nismus 

von Silymarin, dem 

Antihepatotoxischen Prinzip aus Silybum marianum 

(L.) Gaertn. (Studies on Pharmacodynamics, Site and 

Mechanism of Action of Silymarin, the Antihepatotoxic 

Principle from Silybum marianum (L.) Gaertn.). 

Arzneim.-Forsch. 1975, 25 (2), 179–189. 

304. Floersheim, G.L. Treatment of Experimental Poisoning 

Produced by Extracts of Amanita phalloides. Toxicol. 

Appl. Pharmacol. 1975, 34, 499–508. 

305. Vogel, G.; Tuchweber, B.; Trost, W.; Mengs, U. 

Protection by Silibinin Against Amanita phalloides 

Intoxication in Beagles. Toxicol. Appl. Pharmacol. 

1984, 73, 355–362. 

306. Ramellini, G.; Meldolesi, J. Stabilization of Isolated Rat 

Liver Plasma Membranes by Treatment In Vitro with 

Silymarin. Arzneim.-Forsch. 1974, 24 (5), 806–808. 

307. Ramellini, G.; Meldolesi, J. Liver Protection by 

Silymarin: In Vitro Effect on Dissociated Rat Hepatocytes. 

Arzneim.-Forsch. 1976, 26 (1), 69–73. 

308. Vogel, G. The Anti-Amanita Effect of Silymarin. In 



York, 1980; 180–189. 

309. Choppin, J.; Desplaces, A. The Action of Silybin on the 

Mouse Liver in a-Amanitine Poisoning. Arzneim.- 

Forsch. 1979, 29 (1), 63–68. 

310. Flora, K.; Hahn, M.; Rosen, H.; Benner, K. Milk Thistle 

(Silybum marianum) for the Therapy of Liver Disease. 

Am. J. Gastroenterol. 1998, 93 (2), 139–143. 

311. Leng-Peschlow, E.; Strenge-Hesse, A. Die Mariendistel 

(Silybum marianum) und Silymarin als Lebertherapeutikum. 

Z. Phytother. 1991, 12, 162–174. 

312. Leng-Peschlow, E. Properties and Medical Use of 

Flavonolignans (Silymarin) from Silybum marianum. 

Phytother. Res. 1996, 10, S25–S26. 

313. Luper, S. A Review of Plants Used in the Treatment of 

Liver Disease: Part 1. Altern. Med. Rev. 1998, 3 (6), 

410–421. 

314. Luyckx, F.; Scheen, A.J. Pharma-Clinics, le Médicament 

du mois: Le Legalon (Silymarine). Rev. Méd. Liège 

1997, 52 (12), 792–796. 




315. Wellington, K.; Jarvis, B. Silymarin: A Review of Its 

Clinical Properties in the Management of Hepatic 

Disorders. BioDrugs 2001, 15 (7), 465–489. 

316. Muriel, P.; Mourelle, M. Prevention by Silymarin of 

Membrane Alterations in Acute CCl 4 Liver Damage. 

J. Appl. Toxicol. 1990, 10 (4), 275–279. 

317. Bosisio, E.; Cinzia, B.; Ondina, P. Effect of the 

Flavonolignans of Silybum marianum L. on Lipid 

Peroxidation in Rat Liver Microsomes and Freshly 

Isolated Hepatocytes. Pharmacol. Res. 1992, 25 (2), 

147–154. 

318. Carini, R.; Comoglio, A.; Albano, E.; Poli, G. Lipid 

Peroxidation and Irreversible Damage in the Rat 

Hepatocyte Model. Biochem. Pharmacol. 1992, 43 

(10), 2111–2115. 

319. Dehmlow, C.; Jochen, E.; De Groot, H. Inhibition of 

Kupffer Cell Functions as an Explanation for the 

Hepatoprotective Properties of Silybinin. Hepatology 

1996, 23 (4), 749–754. 

320. De LaPuerta, R.; Martinez, E.; Bravo, L.; Ahumada, C. 

Effect of Silymarin on Different Acute Inflammation 

Models and on Leucocyte Migration. J. Pharm. Pharmacol. 

1996, 48, 968–970. 

321. Schuppan, D.; Lang, T.; Gerling, G.; Leng-Peschlow, E.; 

Krumbiegel, G.; Riecken, E.O.; Waldschmidt, J. 

Antifibrotic Effect of Silymarin in Rat Secondary 

Biliary Fibrosis Induced by Duct Obliteration with 

Ethiblock. Z. Gastroenterol. 1995, 32, 45–46. 

322. Fuchs, E.C.; Gressner, A.M.; Weyhem Meyer, R.; 

Weiner, O. Identification of the Antifibrogenic Properties 

of Silybin: Effect on TGF-b and Matrix Gene 

Expression of Hepatic Stellate Cells. Hepatology 1995, 

22, 286A. 

323. Boigk, G.; Stroedter, L.; Herbst, H.; Waldschmidt, J.; 

Riecken, E.O.; Schuppan, D. Silymarin Retards 

Collagen Accumulation in Early and Advanced Biliary 

Fibrosis Secondary to Complete Bile Duct Obliteration 

in Rats. Hepatology 1997, 26 (3), 643–649. 

324. Magliulo, E.; Scevola, D.; Carosi, G.P. Investigations on 

the Actions of Silybin on Regenerating Rat Liver: 

Effects on Kupffer’s Cells. Arzneim.-Forsch. 1979, 29 

(7), 1024–1028. 

325. Machicao, F.; Sonnenbichler, J. Mechanism of the 

Stimulation of RNA Synthesis in Rat Liver Nuclei by 

Silybin. Hoppe-Seyler’s Z. Physiol. Chem. 1977, 358, 

141–147. 

326. Sonnenbichler, J.; Zetl, I. Mechanism of Silybin 

Action V. Effect of Silybin on the Synthesis of 

Ribosomal RNA, mRNA and tRNA in Rat Livers In 

Vivo. Hoppe-Seyler’s Z. Physiol. Chem. 1984, 365 (5), 

555–566. 

327. Sonnenbichler, J.; Goldberg, M.; Hane, L.; Madubunyi, 

I.; Vogl, S.; Zetl, I. Stimulatory Effect of Silybinin on 

the DNA Synthesis in Partially Hepatectomized Rat 

Livers: Non-response in Hepatoma and Other Malign

754 

Cell Lines. Biochem. Pharmacol. 1986, 35 (3), 

538–541. 

328. Sonnenbichler, J.; Zetl, I. Influence of the Flavonolignan 

Derivative Silibinin on Nucleic Acid and Protein 

Synthesis in Liver Cells. Flavonoids Bioflavonoids 

1986, 361–372. 

329. Sonnenbichler, J.; Zetl, I. Biochemical Effects of the 

Flavonolignan Silibinin on RNA, Protein and DNA 

Synthesis in Rat Livers. Prog. Clin. Biol. Res. 1986, 213, 

319–331. 

330. Lorenz, D.; Lücker, P.W.; Mennicke, W.H.; Wetzelsberger, 

N. Pharmacokinetic Studies with Silymarin in 

Human Serum and Bile. Methods Find. Exp. Clin. 

Pharmacol. 1984, 6 (10), 655–661. 

331. Bulles, H.; Bulles, J.; Krumbiegel, G.; Mennicke, W.H.; 

Nitz, D. Untersuchungen zur Verstoffwechselung und 

zur Ausscheidung von Silybin bei der Ratte (Investigation 

of the Metabolism and Excretion of Silybin in the 

Rat). Arzneim.-Forsch. 1975, 25, 902–905. 

332. Flory, P.J.; Krug, G.; Lorenz, D.; Mennicke, H. 

Untersuchungen zur Elimination von Silymarin bei 

Cholezystektomierten Patienten (Studies on Elimination 

of Silymarin in Cholecystectomized Patients). Planta 

Med. 1980, 38, 227–237. 

333. Faulstich, H.; Jahn, W.; Wieland, T. Silybin Inhibition of 

Amatoxin Uptake in the Perfused Rat Liver. Arzneim.- 

Forsch. 1980, 30 (3), 452–454. 

334. Smetana, R.; Hruby, K.; Benesch, B.; Bauer, K.; Jahn, O. 

Laboratory Diagnosis and Surveillance of Amanitin 

Intoxication During Silibinin Therapy. Intensivebehandlung 

1986, 11 (4), 170–175. 

335. Schandalik, R.; Gatti, G.; Perucca, E. Pharmacokinetics 

of Silybin in Bile Following Administration of Silipide 

and Silymarin in Cholecystectomy Patients. Arzneim.- 

Forsch. 1992, 42 (7), 964–968. 

336. Barzaghi, N.; Crema, F.; Gatti, G.; Pifferi, G.; Perucca, 

E. Pharmacokinetic Studies on IdB 1016, a Silybin– 

Phosphatidylcholine Complex, in Healthy Human 

Subjects. Eur. J. Drug Metab. Pharmacokinet. 1990, 15 

(4), 333–338. 

337. Beer, J.H. Der Falsche Pilz (The Wrong Mushroom). 

Schweiz. Med. Wochenschr. 1993, 123 (17), 

892–905. 

338. MacPartland, J.M.; Vilgalys, R.J.; Cubeta, M.A. Mushroom 

Poisoning. Am. Fam. Physician 1997, 55 (5), 


339. Castiella, A.; Arenas, J.I. Utility of Silymarin in 

the Cyclopeptide Syndrome. J. Hepatol. 1994, 21, 

1148. 

340. Kurkin, V.; Lebedev, A.; Zapesochnaya, A.; Avdeeva, 

E.V.; Simonova, G.V.; Lebedev, P.A.; Egorov, V.A.; 

Mizina, P.; Bulatova, M.V. The New Possibilities of the 

Use of Silybum marianum (L.) Gaertn. Fruits. XIXth 

International Conference on Polyphénols, Lille, France, 

Sept 1–4, 1998; 29–30. 




341. Kubicka, J. Rozbor Smrtelnych Otrav Houbami 

Lécenych Kyselinou Tioktovou (Analysis of Fatal 

Intoxications with Mushrooms Treated with Thioctic 

Acid). Cas. Lék. Cesk. 1969, 108, 790–793. 

342. Zaffiri, O.; Centi, R.; Mastroianni, A.; Francescato, F.; 

Bisiani, M. Therapy of Acute Poisoning by Amanita 

phalloides with High Doses of Thioctic Acid. Minerva 

Anestesiol. 1970, 36 (1), 56–57. 

343. Zanninni, L.; Carbone, G.; Stelluti, A. l’Attuale Terapia 

Dell’avvelenamento da Amanita phalloides. Clin. Ter. 

1971, 56, 177. 

344. Dudova, V.; Kubicka, J.; Veselky, J. Thioctic Acid in the 

Treatment of Amanita phalloides Intoxication. In 



York, 1980; 190–191. 

345. Zulik, R.; Kassay, S.F. The Role of Thioctic Acid in the 

Treatment of Amanita phalloides Intoxication. In 



York, 1980; 192–196. 

346. Finestone, A.J.; Berman, R.; Widmer, B.; Markowitz, J.; 

Laquer, U.J. Thioctic Acid Treatment of Acute Mushroom 

Poisoning. PA Med. 1972, 75, 49–51. 

347. Becker, C.E.; Tong, T.G.; Boerner, U.; Roe, R.L.; Scott, 

R.; MacQuarrie, M.B.; Bartter, F. Diagnosis and 

Treatment of Amanita phalloides-Type Mushroom 

Poisoning. West. J. Med. 1976, 125, 100–109. 

348. Culliton, B.J. The Destroying Angel: A Story of a Search 

for an Antidote. Science 1974, 185, 600–601. 

349. Bartter, F.C.; Berkson, B.; Gallelli, J.; Hiranaka, P. 

Thioctic Acid in the Treatment of Poisoning with a- 

Amanitin. In Amanita Toxins and Poisonings; Faulstich, 

H., Kommerell, B., Wieland, T., Eds.; Lubrecht Cramer: 

New York, 1980; 197–202. 

350. Berkson, B.M. Thioctic Acid in Treatment of Hepatotoxic 

Mushroom (Phalloides ) Poisoning. N. Engl. J. 

Med. 1979, 300, 371. 

351. Berkson, B.M. Treatment of Four Delayed-Mushroom 

Poisoning Patients with Thioctic Acid. In Amanita 



203–210. 

352. Alleva, F.R. Thioctic Acid and Mushroom Poisoning. 

Science 1975, 187, 216. 

353. Trost, W.; Lang, W. Effect of Thioctic Acid and 

Silibinin on the Survival Rate in Amanitin and 

Phalloidin Poisoned Mice. IRCS Med. Sci. 1984, 12, 

1079–1080. 

354. Roldan, E.J.; Pérez Lloret, A. Thioctic acid in Amanita 

Poisoning. Crit. Care Med. 1986, 14 (8), 753–754. 

355. Anonymous. Monography: a-Lipoic Acid. Altern. Med. 

Rev. 1998, 3 (4), 308–311. 

356. Bustamante, J.; Lodge, J.K.; Marcocci, L.; Tritschler, 

H.J.; Packer, L.; Rihn, B.H. a-Lipoic Acid in Liver

Metabolism and Disease. Free Radic. Biol. Med. 1988, 

24 (6), 1023–1039. 

357. Olson, K.R.; Woo, O.F.; Pond, S.M. Treatment of 

Mushroom Poisoning. J. Am. Med. Assoc. 1984, 252 

(22), 3130–3131. 

358. Paaso, B.; Harrison, D.C. A New Look at an Old 

Problem: Mushroom Poisoning. Am. J. Med. 1975, 58, 

505–508. 

359. Vesconi, S.; Langer, M. Thioctic Acid in Amanita 

Poisoning. Drs. Vesconi and Langer Reply. Crit. Care 

Med. 1986, 14 (8), 754. 

360. Floersheim, G.L. Treatment of Mushroom Poisoning. 

J. Am. Med. Assoc. 1985, 253 (22), 3252. 

361. Hanrahan, J.P.; Gordon, M.A. Reply to Olson: Treatment 

of Mushroom Poisoning. J. Am. Med. Assoc. 1984, 

252 (22), 3131–3132. 

362. Mitchel, D.H. Amanita Mushroom Poisoning. Ann. Rev. 

Med. 1980, 31, 51–57. 

363. Bartter, F.C. Thioctic Acid and Mushroom Poisoning. 

Science 1975, 187, 216. 

364. Tate, M.; Tufts, E. Treatment of Mushroom Poisoning. 

J. Am. Med. Assoc. 1985, 253 (22), 3252. 

365. Levine, M. Review of Biochemistry, Physiology and 

Clinical Uses of Ascorbic Acid. N. Engl. J. Med. 1986, 

314, 892–902. 

366. Jaeger, A.; Sauder, P.; Kopferschmitt, J.; Berton, C. Les 

Cytoprotecteurs Hépatiques. XXXème Congrès de la 

Société de Toxicologie Clinique, Nancy, France, Sept 

16–17, 1993; 2. 

367. Monthoux, O. Une Intoxication Volontaire par l’Amanite 

Phalloïde et son Traitement: l’Expérience du Dr 

Bastien à Genève en 1981. Schweiz. Z. Pilzkd. 1982, 60 

(11), 194–197. 

368. Bastien, P. l’Intoxication Phalloïdienne à l’Aube de 

1988. Bull. Trim. Féd. Mycol. Dauphiné-Savoie 1988, 

110, 4–7. 

369. Chabré, P.A. Intoxication par l’Amanite Phalloïde: Place 

du Traitement Bastien. Thèse de Pharmacie, Université 

Lyon 1: France, 1995, 98. 

370. Anonymous. Symposium on Clinical Efficacy, Cytoprotection 

and Antifibrinolytic Effects. Scand. 

J. Gastroenterol. 1986, 21 (Suppl. 121), 1–62. 

371. Schneider, S.M.; Borochovitz, D.; Krenzelok, E.P. 

Cimetidine Protection Against a-Amanitin Hepatoxicity 

in Mice: A Potential Model Protection for the Treatment 

of Amanita phalloides Poisoning. Ann. Emerg. Med. 

1987, 16 (10), 1136–1140. 

372. Schneider, S.M.; Vanscoy, G.J.; Michelson, E.A. 

Combination Therapy with Cimetidine, Penicillin and 

Ascorbic Acid for Alpha-Amanitin Toxicity in Mice. 

Ann. Emerg. Med. 1989, 18, 482. 

373. Dawson, J.R.; Norbeck, K.; Anundi, I.; Moldeus, P. The 

Effectiveness of N-Acetylcysteine in Isolated Hepatocytes 

Against the Toxicity of Paracetamol, Acrolein and 

Paraquat. Arch. Toxicol. 1984, 55 (1), 11–15. 




374. Flanagan, R.J. The Role of Acetylcysteine in Clinical 

Toxicology. Med. Toxicol. 1987, 2, 93–104. 

375. Kawaji, A.; Sone, T.; Natsuki, R.; Isobe, M.; 

Takabatake, E.; Yamaura, Y. In Vitro Toxicity Test of 

Poisonous Mushroom Extracts with Isolated Rat 

Hepatocytes. J. Toxicol. Sci. 1990, 15 (3), 145–156. 

376. Schneider, S.M.; Michelson, E.A.; Vanscoy, G.J. Failure 

of N-Acetylcysteine to Reduce Alpha-Amanitin Toxicity. 

J. Appl. Toxicol. 1992, 12 (2), 141–142. 

377. Usadel, K.H.; Wdowinski, J.; Schwedes, U.; Faulstich, 

H.; Röttger, G.; Hübner, K. Effects of Somatotropin, 

Insulin, “Liver Growth Factor” and Silybin on Liver 

Regeneration After a-Amanitin Poisoning in the Rat. In 



York, 1980; 216–224. 

378. Harrison, P.M.; Hughes, R.D.; Forbes, A.; Portmann, B.; 

Alexander, G.J.M.; Williams, R. Failure of Insulin and 

Glucagon Infusion to Stimulate Liver Regeneration in 

Fulminant Hepatic Failure. J. Hepatol. 1990, 10, 

332–336. 

379. Rakeka, J. A Double-Blinded Randomized Trial of 

Hydrocortisone in Acute Hepatic Failure: Acute Hepatic 

Failure Study Group. Gastroenterology 1979, 76, 1297. 

380. Chang, I.M.; Yun, H.S.; Kim, Y.S.; Ahn, J.W. Aucubin: 

Potential Antidote for a-Amanitin Poisoning. Clin. 

Toxicol. 1984, 22 (1), 77–85. 

381. Bianco, A.; Bonini, C.C.; Iavarone, C.; Trogolo, C. 

Structure Elucidation of Eucommioside (2 00 -O-b-D- 

Glucopyranosyl Eucommiol) from Eucommia ulmoides. 

Phytochemistry 1982, 21 (1), 201–203. 

382. Chang, I.M.; Yamaura, Y. Aucubin: A New Antidote for 

Poisonous Amanita Mushrooms. Phytother. Res. 1993, 

7, 53–56. 

383. Bernini, R.; Iavarone, C.; Trogolo, C. 1-O-b-Glucopyranosyleucommiol, 

an Iridoid Glucoside from Aucuba 

japonica. Phytochemistry 1984, 23 (7), 1431–1433. 

384. Chang, I.M. Liver-Protective Activities of Aucubin 

Derived from Traditional Oriental Medicine. Res. 

Commun. Mol. Pathol. Pharmacol. 1998, 102 (2), 

189–204. 

385. Lee, D.H.; Cho, I.G.; Park, M.S.; Kim, K.N.; Chang, 

I.M.; Mar, W. Studies on the Possible Mechanisms of 

Protective Activity Against a-Amanitin Poisoning by 

Aucubin. Arch. Pharm. Res. 2001, 24 (1), 55–63. 

386. Suh, N.J.; Shim, C.K.; Lee, M.H.; Kim, S.K.; Chang, 

I.M. Pharmacokinetic Study of an Iridoid Glucoside: 

Aucubin. Pharm. Res. 1991, 8, 1059–1063. 

387. Weinges, K.; Kloss, P.; Henkels, W.D. Natural Products 

from Medicinal Plants. XVII. Pricoside II, a New 6- 

Vanilloyl-catapol from Picrorhiza kuroa Royle and 

Benth. Justus Liebigs Ann. Chem. 1972, 759, 173–182. 

388. Ansari, R.A.; Aswal, B.S.; Chander, R.; Dhawan, B.N.; 

Garg, N.K.; Kapoor, N.K.; Kulshreshtha, D.K.; Mehdi, 

H.; Mehrotra, B.N.; Patnaik, G.K.; Sharma, S.K.

756 

Hepatoprotective Activity of Kutkin—The Iridoid 

Glycoside Mixture of Picrorhiza kurrooa. Indian 

J. Med. Res. 1988, 401–404. 

389. Dwivedi, Y.; Rastogi, R.; Garg, N.K.; Dhawan, B.N. 

Effects of Picroliv, the Active Principle of Picrorhiza 

kurroa, on Biochemical Changes in Rat Liver Poisoned 

by Amanita phalloides. Chung-kuo Yao Li Hsueh Pao 

1992, 13 (3), 197–200. 

390. Floersheim, G.L.; Bieri, A.; Koenig, R.; Pletscher, A. 

Protection Against Amanita phalloides by the Iridoid 

Glycoside Mixture of Picrorhiza kurroa (Kutkin). 

Agents Actions 1990, 29 (3/4), 386–387. 

391. Chen, N.; Bowles, M.R.; Pond, S.M. Polyclonal 

Amanitin-Specific Antibodies: Production and Cytoprotective 

Properties In Vitro. Biochem. Pharmacol. 1993, 

46 (2), 327–329. 

392. Faultstich, H.; Kirchner, K.; Derenzini, M. Strongly 

Enhanced Toxicity of the Mushroom Toxin Alpha- 

Amanitin by an Amatoxin-Specific Fab or Monoclonal 

Antibody. Toxicon 1998, 26 (5), 491–499. 

393. Tempé J.D.; Lutun, P.; Schneider, F.; Bilbault, P.; 

Marcoux, L. Hépatites Aiguës Toxiques. Indications et 

Résultats de la Transplantation Hépatique. XXXIème 

Congrès de la Société de Toxicologie Clinique, Nancy, 

France, Sept 16–17, 1993; Part I, 1–29. 

394. Gubernatis, G.; Pichlmayr, R.; Kemnitz, J.; Gratz, K. 

Auxiliary Partial Orthotopic Liver Transplantation 

(APOLT) for Fulminant Hepatic Failure: First 

Successful Case Report. World J. Surg. 1991, 15, 

660–665. 

395. Boudjema, K.; Siméoni, U.; Becmeur, F.; Schiffer, F.; 

Odeh, M.; Chenard, M.P.; Bellocq, J.P.; Wolf, P.; 

Gelsert, J.; Sauvage, P.; Cinquabre, J.; Jaeck, D. 

Transplantation Hépatique Auxiliaire dans le Traitement 

de l’Hépatite Fulminante chez l’Enfant: À Propos d’Une 

Observation. Réa. Urg. 1993, 3, 316. 

396. Moritz, M.J.; Jarrell, B.E.; Munoz, S.J.; Maddrey, W.C. 

Regeneration of the Native Liver After Heterotopic 

Liver Transplantation for Fulminant Hepatic Failure. 

Transplantation 1992, 55 (4), 952–954. 

397. Chenard-Neu, M.P.; Boudjema, K.; Bernuau, J.; Degott, 

C.; Belghiti, J.; Cherqui, D.; Costes, V.; Domergue, J.; 

Durand, F.; Ehrard, J.; De Hemptinne, B.; Gubernatis, 

G.; Hadengue, A.; Kemnitz, J.; McCarthy, M.; Maschek, 

H.; Mentha, G.; Oldhafer, K.; Portmann, B.; Praet, M.; 

Ringers, J.; Rogiers, X.; Rubbia, L.; Schalm, S.; Ten 

Kate, F.; Terpstra, O.; Van Hoek, B.; Williams, R.; 

Zafrani, E.S.; Cinqualbre, J.; Wolf, P.; Jaeck, D.; 

Bellocq, J.P. Auxiliary Liver Transplantation: 

Regeneration of the Native Liver and Outcome in 

30 Patients with Fulminant Hepatic Failure—A Multicenter 

European Study. Hepatology 1996, 23, 

1119–1127. 

398. Duffy, T.J. Liver Transplantation for Victims of Amanita 

Mushroom Poisoning. McIlvainea 1989, 9 (1), 4–5. 




399. Frohburg, E.; Stölzel, U.; Lenz, K.; Schäfer, J.H.; Tung, 

L.C.; Riecken, E.O. Prognostic Indicators in 

Fulminant Hepatic Failure. Z. Gastroenterol. 1992, 30, 

571–575. 

400. Caraceni, P.; Van Thiel, D.H. Acute Liver Failure. 

Lancet 1995, 345, 163–169. 

401. Castells, A.; Salmeron, J.M.; Navasa, M.; Rimola, A.; 

Salö, J.; Andreu, H.; Mas, A.; Rodès, J. Liver 

Transplantation for Acute Liver Failure: Analysis of 

Applicability. Gastroenterology 1993, 105, 532–538. 

402. Chapman, R.W.; Forman, D.; Perto, R.; Smallwood, R. 

Liver Transplantation for Acute Hepatic Failure? Lancet 

1990, 335, 32–35. 

403. Lake, J.R.; Sussman, N.L. Determining Prognosis in 

Patients with Fulminant Hepatic Failure: When You 

Absolutely Positively Have to Know the Answer. 

Hepatology 1995, 21 (3), 879–881. 

404. Jaeger, A.; Kopferschmitt, J.; Flesch, F.; Berton, C.; 

Levenos, H.; Sauder, P. Liver Transplantation for 

Amanita Poisoning. Congress of Anti-Poisons Centre, 

Istambul, Turkey, May 24–27, 1992; 103. 

405. O’Grady, J.G.; Alexander, G.J.M.; Hayllar, K.M.; 

Williams, R. Early Indicators of Prognosis in 

Fulminant Hepatic Failure. Gastroenterology 1989, 97, 

439–445. 

406. Shakil, A.O.; Kramer, D.; Mazariegos, G.V.; Fung, J.J.; 

Rakela, J. Acute Liver Failure: Clinical Features, 

Outcome Analysis, and Applicability of Prognostic 

Criteria. Liver Transplant. 2000, 6 (2), 163–169. 

407. Bernuau, J.; Samuel, D.; Durand, F.; Saliba, F.; 

Bourlière, M.; Adam, R.; Gugenheim, J.; Castaing, D.; 

Bismuth, H.; Rueff, B.; Erfinger, S.; Benhamou, J.P. 

Criteria for Emergency Liver Transplantation in Patients 

with Acute Viral Hepatitis and Factor V (FV) Below 

50% of Normal: A Prospective Study. Hepatology 1991, 

14, 49A. 

408. Bismuth, H.; Samuel, D.; Gugenheim, J.; Castaing, D.; 

Bernuau, J.; Rueff, B.; Benhamou, J.P. Emergency Liver 

Transplantation for Fulminant Hepatitis. Ann. Intern. 

Med. 1987, 107, 337–341. 

409. Bismuth, H.; Samuel, D.; Castaing, D.; Adam, R.; 

Saliba, F.; Johann, M.; Azoulay, D.; Ducot, B.; Chiche, 

L. Orthotopic Liver Transplantation in Fulminant and 

Subfulminant Hepatitis. The Paul Brousse Experience. 

Ann. Surg. 1995, 222 (2), 109–119. 

410. Pereira, L.M.M.B.; Langley, P.G.; Hayllar, K.M.; 

Tredger, J.M.; Williams, R. Coagulation Factor V and 

VIII/V Ratio as Predictors of Outcome in Paracetamol 

Induced Fulminant Hepatic Failure: Relation to Other 

Prognostic Indicators. Gut 1992, 33, 98–102. 

411. Lee, W.M.; Galbraith, R.M.; Watt, G.H.; Hughes, R.D.; 

McIntire, D.D.; Hoffman, B.J.; Williams, R. Predicting 

Survival in Fulminant Hepatic Failure Using Serum Gc 

Protein Concentrations. Hepatology 1995, 21 (1), 

101–105.

412. Trey, C.; Davidson, L.S. The Management of Fulminant 

Hepatic Failure. In Progress in Liver Disease; Popper, 

H., Schaffner, F., Eds.; Grune and Stratton Publishers: 

New York, 1970; 282–298. 

413. Bernuau, J.; Benhamou, J.P. Classifying Acute Liver 

Failure. Lancet 1993, 342, 252–253. 

414. Edmond, J.C.; Aran, P.P.; Whitington, P.F.; Broelsch, 

C.E.; Baker, A.L. Liver Transplantation in the Management 

of Fulminant Hepatic Failure. Gastroenterology 

1989, 96, 1583–1588. 

415. O’Grady, J.G.; Schalm, S.W.; Williams, R. Acute Liver 

Failure: Redefining the Syndromes. Lancet 1993, 342, 

273–275. 

416. Bernuau, J.; Goudeau, A.; Poynard, T.; Dubois, F.; 

Lesage, G.; Yvonnet, B.; Degott, C.; Bezeaud, A.; Rueff, 

B.; Benhamou, J.P. Multivariate Analysis of Prognostic 

Factors in Fulminant Hepatitis B. Hepatology 1986, 6 

(4), 648–651. 




417. Pauwels, A.; Mostefa-Kara, N.; Florent, C.; Levy, V.G. 

Emergency Liver Transplantation for Acute Liver 

Failure. Evaluation of London and Clichy Criteria. 

J. Hepatol. 1993, 17, 124–127. 

418. Izumi, S.; Langley, P.G.; Wendon, J.; Ellis, A.J.; 

Pernambuco, J.R.B.; Hughes, R.D.; Williams, R. 

Coagulation Factor V Levels as a Prognostic Indicator 

in Fulminant Hepatic Failure. Hepatology 1996, 23 (6), 

1507–1511. 

419. Harrison, P.M.; O’Grady, J.G.O.; Keays, R.T.; 

Alexander, G.J.M.; Williams, R. Serial Prothrombin 

Time as Prognostic Indicator in Paracetamol-Induced 

Fulminant Hepatic Failure. Br. Med. J. 1990, 301, 

964–966. 

420. Christensen, E.; Bremmelgaard, A.; Bahnsen, M.; Buch 

Andreasen, P.; Tygstrup, N. Prediction of Fatality in 

Fulminant Hepatic Failure. Scand. J. Gastroenterol. 

1984, 19 (1), 90–96.

9. Treatment of Amatoxin Poisoning-20 year retrospective analysis

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