amanitins and Hepatic-Encephalopathy

Topics: Acute Disease; Adult; Aged; Amanitins; Female; Glasgow Coma Scale; Hepatic Encephalopathy; Hong Kong; Humans; Liver Transplantation; Male; Middle Aged; Mushroom Poisoning

Topics: Acetylcysteine; Adult; Amanita; Amanitins; Cause of Death; Combined Modality Therapy; Critical Care; Diagnosis, Differential; Hepatic Encephalopathy; Humans; Liver Function Tests; Liver Transplantation; Male; Mushroom Poisoning; Prognosis; Silybin; Silymarin

The authors describe frequency and importance of poisoning by Amanita phalloides. There are demonstrated the different toxins and their biochemical properties. The typical clinical symptoms of the intoxication by Amanita phalloides with vourse in two phases (1. gastrointestinal phase, 2. hepatonephrotic phase) are shown. The possibilities of diagnostic and differentialdiagnostic and the problems of therapy are discussed. It is pointed out, that in a modern treatment there must be given Penicillin-G-Natrium in high dosage as early as possible, also in cases of questionableness. Hemodialysis is only of effect till 40 hours after ingestion of Amanita.

Topics: Amanita; Amanitins; Blood Coagulation Disorders; Child; Diagnosis, Differential; Female; Hepatic Encephalopathy; Humans; Mushroom Poisoning; Penicillin G

On the basis of experimental and clinical results evidence accumulates that supportive therapy is still the milestone in the therapy of death cap poisoning. Today the letality is 20%. The main cause of the intoxication are the amatoxines which inhibit DNA dependent RNA Polymerase II or B. Parts of the supportive therapy are: diuresis with 150--200 ml urin/hour, careful corrections of disturbances in electrolyte and acid-base-metabolism, oral administration of charcoal and oral gut sterilization. In spite of a multitude of experimental and clinical reports on the effectivity of Penicillin G, thiocticacid and steroids there are no controlled studies to demonstrate the advantage of one regimen over the other. The time course of resorption and excretion of amatoxines clearly shows that hemoperfusion and/or hemodialysis are only of value if applied within the first 24 hours after poisoning. At this time neither anamnestic nor biochemical data give any clues to the probable course of the disease. Heterologous baboon liver perfusion may be lifesaving in coma hepaticum grade IV, but the small amount of cases so far does not yet allow any comments on its effectivity.

Topics: Amanita; Amanitins; Animals; Hemoperfusion; Hepatic Encephalopathy; Humans; Liver; Mushroom Poisoning; Papio; Perfusion; Renal Dialysis; Time

Acute liver failure (ALF) is associated with high mortality, and a poor understanding of the underlying pathophysiology has resulted in a lack of effective treatments so far. Here, using an amatoxin-induced rhesus monkey model of ALF, we panoramically revealed the cellular and molecular events that lead to the development of ALF. The challenged monkeys with toxins underwent a typical course of ALF including severe hepatic injury, systemic inflammation and eventual death. Adaptive immune was not noticeably disturbed throughout the progress of ALF. A systematic examination of serum factors and cytokines revealed that IL-6 increase was the most rapid and drastic. Interestingly, we found that IL-6 was mainly produced by circulating monocytes. Furthermore, ablation of monocyte-derived IL-6 in mice decreased liver injury and systemic inflammation following chemical injection. Our findings reveal a critical role of circulating monocytes in initiating and accelerating ALF, indicating a potential therapeutic target in clinical treatment for ALF.

Topics: Alanine Transaminase; Amanitins; Animals; Aspartate Aminotransferases; Cytokines; Disease Progression; Gene Expression; Hepatic Encephalopathy; Interleukin-6; L-Lactate Dehydrogenase; Lipopolysaccharides; Liver Failure, Acute; Liver Function Tests; Macaca mulatta; Mice; Monocytes

An extracorporeal bioartificial liver (BAL) that could prevent death from hepatic encephalopathy in acute hepatic insufficiency was aimed to develop. A functional human hepatocellular carcinoma cell line (FLC-4) was cultured in a radial-flow bioreactor. The function of the BAL was tested in mini-pigs with acute hepatic failure induced by alpha-amanitin and lipopolysaccharide. When the BAL system was connected with cultured FLC-4 to three pigs with hepatic dysfunction, all demonstrated electroencephalographic improvement and survived. Relatively low plasma concentrations of S-100 beta protein, as a marker of astrocytic damage, from pigs with hepatic failure during BAL therapy were noted. BAL therapy can prevent irreversible brain damage from hepatic encephalopathy in experimental acute hepatic failure.

Topics: Amanitins; Animals; Bioreactors; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Hepatic Encephalopathy; Lipopolysaccharides; Liver, Artificial; Male; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Swine; Swine, Miniature

For the development of an artificial liver support system, a clinically relevant large-animal model of fulminant hepatic failure (FHF) is indispensable. Although several large-animal models have been reported so far, they have not been entirely satisfactory. Recently, we have developed a new porcine model of FHF by means of intraportal administration of 0.1 mg/kg of alpha-amanitin and 1 microg/kg of lipopolysaccharide (LPS). This model has the following superior features: 100% mortality within 5 days along with a marked elevation of aspartate transaminase (AST) levels to around 10,000 IU/l, and severe metabolic disorders such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia; an onset of hepatic encephalopathy and a significant increase in intracranial pressure immediately before death; a reversal of FHF by orthotopic liver transplantation, proving that the toxicity is liver-specific and that the graft liver is unaffected; and the capability of the damaged liver to recover and achieve both morphological and functional regeneration in 1 week if supported by an efficient auxiliary graft. Because this porcine model satisfies many of the required criteria of an optimal FHF model, it is expected to provide a useful tool for the study of FHF and the development of new therapies.

Topics: Amanitins; Animals; Dogs; Hepatic Encephalopathy; Lipopolysaccharides; Liver Failure; Liver Transplantation; Male; Models, Animal; Swine

Alpha-amanitin, the main toxin of the death cap fungus (Amanita phalloides) is one of the most dangerous natural poison. This toxin damages eukaryotic cells by inhibiting their transcription. Lesions are seen in cells with rapid protein synthesis, particular in liver and renal cells, even at low toxin concentrations. Without adequate intensive therapy, the outcome of alpha-amanitin poisoning is very poor. This article reports various courses of amanitin intoxication in a family. In 3/4 patients, severe hepatic failure developed as assessed by a decrease of all coagulation factors, mainly Quick's test and factor V (< 10%-15%). Despite vigorous replacement of coagulation factors, in 1 of the patients orthotopic liver transplantation had to be performed on day 4, whereas in all other patients liver function improved spontaneously. All patients survived their intoxication. Both the pharmacological basis and clinical manifestations of Amanita intoxication are discussed. On this basis a treatment scheme is presented which the authors believe may be useful to clinicians.

Topics: Adult; Aged; Amanita; Amanitins; Child, Preschool; Critical Care; Emigration and Immigration; Female; Germany; Hepatic Encephalopathy; Humans; Liver Function Tests; Liver Transplantation; Male; Mushroom Poisoning; Russia

Topics: Acute Disease; Adolescent; Adult; Amanitins; Disseminated Intravascular Coagulation; Female; Hepatic Encephalopathy; Hepatitis; Humans; Liver; Male; Mushroom Poisoning

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Amanita; Amanitins; Critical Care; Female; Hepatic Encephalopathy; Humans; Male; Middle Aged; Mushroom Poisoning; Prognosis

Poisonous species of fungi in Germany are very few. Dangerous is the ingestion of raw, spoiled or poisonous mushrooms. There exist no reliable tests to determine whether a mushroom is safe except by expert examination and identification of the mushroom. In clinical practice the classification of mushroom poisoning is possible in muscarine-syndrome, gastroenteritic syndrome and in two-phase-syndrome. 90-95% of lethal mushroom poisonings are due to ingestion of Amanita phalloides. In severe cases extensive hepatic necrosis occurs, characterized by profound abnormalities in liver function caused by hepatic coma. In deep coma mortality rates amount to 70% or more. A new therapeutic measure (coated charcoal hemoperfusion)-first applied in liver failure by Chang (1972) and Williams (1973)-has been performed in 3 patients with severe poisoning after ingestion of Amanita phalloides (each patient had eaten at least 7-10 fungi Amanita phalloides). Two of the patients survived.

Topics: Adult; Amanitins; Charcoal; Female; Hepatic Encephalopathy; Humans; Male; Methods; Middle Aged; Mushroom Poisoning; Renal Dialysis