Amanita poisoning: treatment and the role of liver transplantation

Fatal mushroom poisoning has long been recognized as a major health problem in western Europe and more recently in the United States. The majority of deaths are attributable to the genus Amanita. Amanita phalloides (death cap) has been found with increasing frequency across the United States and presents a significant health hazard in this country to those who pick and consume wild mushrooms. This article discusses the pharmacologic basis and clinical manifestations of Amanita intoxication. It outlines the rationale of various treatment modalities and, from these, summarizes a protocol that the authors believe will be useful to the clinician. In addition, two patients are presented who underwent successful orthotopic liver transplantation for fulminant hepatic failure secondary to Amanita poisoning. The role of liver transplantation both acutely and as treatment for chronic active hepatitis secondary to severe intoxication is discussed.     

Mushroom poisoning: the role of orthotopic liver transplantation.

Mushroom poisoning, mycetismus, is a well-recognized cause of fulminant hepatic failure in Western Europe and is increasingly seen in the United States. We present a case of fulminant hepatic failure secondary to mushroom poisoning treated successfully with an orthotopic liver transplant.     

Recovery from severe hepatitis caused by mushroom poisoning without liver transplantation.

BACKGROUND & AIMS: Toxic mushroom poisoning leads to a variety of clinical outcomes ranging from self-limited gastrointestinal symptoms to fulminant hepatic failure requiring orthotopic liver transplantation. We reviewed the outcomes of patients with severe acute hepatitis secondary to mushroom poisoning, treated with contemporary modalities. METHODS: We retrospectively reviewed patients admitted to our institution over a 5-year period with elevated transaminase levels (>1000 IU/L) attributed to recent mushroom ingestion. The patients' clinical course, laboratory data, and treatment regimen were recorded and analyzed. RESULTS: Eight patients who presented with severe hepatitis after mushroom ingestion qualified for analysis. The mean peak serum levels were: aspartate transaminase 5488 IU/L, alanine transaminase 7618 IU/L, and total bilirubin 10.5 mg/dL. The mean peak prothrombin time was 31 seconds. One patient developed acute renal failure requiring hemodialysis. Three patients developed encephalopathy ranging from grade I to III. All 8 patients survived without significant morbidity or need for liver transplantation. Subgroup analysis revealed that older patients spent more days in the intensive care unit and subsequently had longer hospital stays. The older group also had a trend toward more severe laboratory abnormalities. CONCLUSIONS: Patients with severe hepatitis from mushroom poisoning are thought to have a poor prognosis and frequently need liver transplantation for survival. We suggest that with early and aggressive multidisciplinary care, such patients have improved outcomes and may avoid liver transplantation.     

Early Molecular Adsorbents Recirculating System Treatment of Amanita Mushroom Poisoning

Acute poisoning due to ingestion of hepatotoxic Amanita sp. mushrooms can result in a spectrum of symptoms, from mild gastrointestinal discomfort to life‐threatening acute liver failure. With conventional treatment, Amanita phalloides mushroom poisoning carries a substantial risk of mortality and many patients require liver transplantation. The molecular adsorbent recirculating system (MARS) is an artificial liver support system that can partly compensate for the detoxifying function of the liver by removing albumin‐bound and water‐soluble toxins from blood. This treatment has been used in acute liver failure to enable native liver recovery and as a bridging treatment to liver transplantation. The aim of the study is to evaluate the outcome of 10 patients with Amanita mushroom poisoning who were treated with MARS. The study was a retrospectively analyzed case series. Ten adult patients with accidental Amanita poisoning of varying severity were treated in a liver disease specialized intensive care unit from 2001 to 2007. All patients received MARS treatment and standard medical therapy for mushroom poisoning. The demographic, laboratory, and clinical data from each patient were recorded upon admission. The one‐year survival and need for liver transplantation were documented. The median times from mushroom ingestion to first‐aid at a local hospital and to MARS treatment were 18 h (range 14–36 h) and 48 h (range 26–78 h), respectively. All 10 patients survived longer than one year. One patient underwent a successful liver transplantation. No serious adverse side‐effects were observed with the MARS treatment. In conclusion, MARS treatment seems to offer a safe and effective treatment option in Amanita mushroom poisoning.     

Liver transplantation in mushroom poisoning

Liver transplantation plays an important role in the treatment of patients with fulminant hepatic failure (FHF). Early determination of prognosis in cases of FHF is important to allow prompt decision-making regarding the need for liver transplantation. Mushroom poisoning is a rare cause of FHF, and as a result, prognostic criteria are not well recognized. It appears that the severity of coagulopathy and encephalopathy predicts a poor outcome, whereas the degree of bilirubin elevation may not. We present a case of FHF related to mushroom poisoning that required liver transplantation. The clinical presentation, medical management, and prognostic criteria in mushroom poisoning are discussed.     

Total hepatectomy and liver transplantation as a two-stage procedure for fulminant hepatic failure: A safe procedure in exceptional circumstances

AIM: To evaluate the outcomes of two-stage liver transplant at a single institution, between 1993 and March 2015.METHODS: We reviewed our institutional experience with emergency hepatectomy followed by transplantation for fulminant liver failure over a twenty-year period. A retrospective review of a prospectively maintained liver transplant database was undertaken at a national liver transplant centre. Demographic data, clinical presentation, preoperative investigations, cardiocirculatory parameters, operative and postoperative data were recorded.RESULTS: In the study period, six two-stage liver transplants were undertaken. Indications for transplantation included acute paracetamol poisoning(n = 3), fulminant hepatitis A(n = 1), trauma(n = 1) and exertional heat stroke(n = 1). Anhepatic time ranged from 330 to 2640 min. All patients demonstrated systemic inflammatory response syndrome in the first post-operative week and the incidence of sepsis was high at 50%. There was one mortality, secondary to cardiac arrest 12 h following re-perfusion. Two patients required re-transplantation secondary to arterial thrombosis. At a median follow-up of 112 mo, 5 of 6 patients are alive and without evidence of graft dysfunciton.CONCLUSION: Two-stage liver transplantation represents a safe and potentially life-saving treatment for carefully selected exceptional cases of fulminant hepatic failure.     

Treatment of hepatic failure secondary to isoniazid hepatitis with liver transplantation

Summary Two patients with liver failure secondary to isoniazid hepatotoxicity were successfully treated with orthotopic liver transplantation. A 49-year-old man received isoniazid prophylaxis for a positive tuberculin test, and a 60-year-old woman was treated for active pulmonary tuberculosis with isoniazid, rifampin, and pyrazinamide. Both patients developed hepatic failure 4 and 1.5 months after initiation of antituberculous drug therapy, respectively. Liver transplantation was performed for progressive hepatic failure and was successful in both patients. The patient with active pulmonary tuberculosis was successfully treated with a modified antituberculous drug regimen while taking standard doses of immunosuppressive drugs after transplantation. In conclusion, liver transplantation is feasible and effective therapy for patients with isoniazid-induced hepatic failure, and active pulmonary tuberculosis may represent a relative rather than absolute contraindication to transplantation.     

Liver failure due to mushroom poisoning: clinical course and new treatment perspectives

Mushroom poisoning, mainly due to the Amanita genus, is an infrequent cause of liver failure in our environment. However, because of its high morbidity and mortality, it constitutes a medical emergency. The characteristic initial symptoms of vomiting, abdominal pain, and diarrhea are nonspecific and may be confused with gastroenteritis. If correct and early treatment is not given, renal and hepatic failure can develop, sometimes requiring liver transplantation. We present three cases of mushroom poisoning, which presented a different clinical course ranging from complete recovery with traditional medical treatment to severe acute liver failure requiring transplantation in one patient and albumin dialysis (molecular absorbent recycling system [MARS]) in another with favorable outcome. Although controlled clinical studies of the treatment of mushroom poisoning are lacking, recommendations based on the experience of various authors have been established. Penicillin G and silymarin seem to be useful. The development of new techniques of extracorporeal detoxification, mainly MARS, may represent an important support system in the treatment of these patients.     

Mushroom poisoning—from diarrhea to liver transplantation

Mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common species. The typical symptoms of nausea, vomiting, abdominal pain, and diarrhea are nonspecific and can be mistaken for gastroenteritis. If not adequately treated, hepatic and renal failure may ensue within several days of ingestion. In this case series, patients poisoned with Amanita virosa are described with a spectrum of clinical presentations and outcomes ranging from complete recovery to fulminant hepatic failure. Although there are no controlled clinical trials, a few anecdotal studies provide the basis for regimens recommended to treat Amanita poisoning. Use of i.v. penicillin G is supported by most reports. Silibinin, although preferred over penicillin, is not easily available in the United States. In those with acute liver failure, liver transplantation can be life saving.     

Mushroom poisoning with Amanita phalloides - a report of four cases

Amanita mushroom poisoning is a rare but serious occurrence. Physicians need to recognize the phalloides syndrome promptly and to institute effective treatment as soon as possible in order to avoid the often fatal complications. The authors report four cases of Amanita poisoning, two of which resulted in fulminant hepatic failure and required orthotopic liver transplantation. The clinical symptoms and signs, laboratory alterations, and therapeutic options available are discussed.     

Extracorporeal albumin dialysis in patients with Amanita phalloides poisoning

Background: Ingestion of Amanita phalloides is the most common cause of lethal mushroom poisoning. The relative late onset of symptoms is a distinct diagnostic feature of Amanita intoxication and also the main reason of failure for extracorporeal removal of Amanita‐specific toxins from the gut and circulation. Patients and methods: Extracorporeal albumin dialysis (ECAD) has been used on six consecutive patients admitted after A. phalloides poisoning with acute liver failure (ALF). Results: Six patients, with mean age of 46 years (range: 9–70 years), underwent one to three ECAD treatments. The mean time from mushroom ingestion until the first ECAD treatment was 76 h. Two patients regenerated spontaneously under ECAD treatment and orthotopic liver transplantation (OLT) could be avoided. Two patients were successfully bridged to OLT and one patient died because of cerebral herniation. One patient was treated with ECAD immediately after OLT because of the graft dysfunction and survived without re‐transplantation. Conclusion: ECAD appeared to be a successful treatment perspective in supporting liver regeneration or in sufficient bridging to OLT and also in treatment of graft dysfunction after OLT in patients with A. phalloides poisoning.     

Liver Transplantation Avoided in Patients With Fulminant Hepatic Failure Who Received Albumin Dialysis With the Molecular Adsorbent Recirculating System While on the Waiting List: Impact of the Duration of Therapy

Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74‐month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, P = 0.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all P < 0.001). In the whole study population, a MARS therapy duration ≥15 h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48–1743.11, P = 0.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (≥15 h) could be necessary to expect significant liver function improvement.     

Critical role of c-jun (NH2) terminal kinase in paracetamol- induced acute liver failure

BACKGROUND: Acute hepatic failure secondary to paracetamol poisoning is associated with high mortality. C-jun (NH2) terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and is a key intracellular signalling molecule involved in controlling the fate of cells. AIM: To examine the role of JNK in paracetamol-induced acute liver failure (ALF). METHODS: A previously developed mouse model of paracetamol poisoning was used to examine the role of JNK in paracetamol-induced ALF. RESULTS: Paracetamol-induced hepatic JNK activation both in human and murine paracetamol hepatotoxicity and in our murine model preceded the onset of hepatocyte death. JNK inhibition in vivo (using two JNK inhibitors with different mechanisms of action) markedly reduced mortality in murine paracetamol hepatotoxicity, with a significant reduction in hepatic necrosis and apoptosis. In addition, delayed administration of the JNK inhibitor was more effective than N-acetylcysteine after paracetamol poisoning in mice. JNK inhibition was not protective in acute carbon tetrachloride-mediated or anti-Fas antibody-mediated hepatic injury, suggesting specificity for the role of JNK in paracetamol hepatotoxicity. Furthermore, disruption of the JNK1 or JNK2 genes did not protect against paracetamol-induced hepatic damage. Pharmacological JNK inhibition had no effect on paracetamol metabolism, but markedly inhibited hepatic tumour necrosis foctor alpha (TNF alpha) production after paracetamol poisoning. CONCLUSIONS: These data demonstrated a central role for JNK in the pathogenesis of paracetamol-induced liver failure, thereby identifying JNK as an important therapeutic target in the treatment of paracetamol hepatotoxicity.     

Liver transplantation for disulfiram-induced hepatic failure

Fulminant hepatitis is a rare but potentially fatal adverse reaction that may occur after the use of disulfiram. A patient without a known history of liver disease was transplanted for fulminant hepatic failure secondary to disulfiram. A high index of suspicion and aggressive therapeutic approaches are essential for the prompt diagnosis and treatment of disulfiram-induced hepatic failure. The clinical presentation, histopathology, treatment, and all cases of disulfiram-induced hepatic failure reported in the English literature are reviewed. The role of orthotopic liver transplantation in a case of disulfiram-induced hepatic failure is discussed.     

Fatal mushroom poisoning caused by Amanita virosa in Thailand

Consumption of toxic mushrooms belonging to the genus Amanita frequently leads to severe gastrointestinal distress followed by acute hepatic failure with a fatal outcome. In Thailand, valuable information as to the locally prevalent poisonous species, the preferred habitat and the management of suspected victims of intoxication is basically non-existent. We report here 5 cases of fatal poisoning with Amanita virosa having occurred in a family residing in the northeast of Thailand who as countless others had enjoyed mushroom gathering as a pasttime. Within 4 to 6 days after ingestion of the mushrooms, all had succumbed to acute hepatic failure with subsequent hepatoencephalopathy. Treatment modalities exist in the form of penicillin and silibinin, or thioctic acid administration followed by plasmapheresis. In cases taking a lethal course apparent from the results of liver biochemistry, liver transplantation is clearly indicated. In order to prevent mushroom poisoning altogether, educating the general population to that end certainly presents the method of choice.     

Urgent liver transplantation for acute liver failure due to parvovirus B19 infection complicated by primary Epstein-Barr virus and cytomegalovirus infections and aplastic anaemia

An 11-year-old boy presented with hepatic failure secondary to parvovirus B19 infection, requiring urgent liver transplantation. His recovery was complicated by primary Epstein-Barr virus and cytomegalovirus infections. He subsequently developed aplastic anaemia that has been refractory to antithymocyte globulin and cyclosporine therapy and may now require bone marrow transplantation. We present this case to emphasize parvovirus as a rare cause of hepatic failure and of aplastic anaemia as a complication of the virus.     

Hepatic venoocclusive disease and perisinusoidal fibrosis secondary to arsenic poisoning

Hepatic injury secondary to arsenic poisoning has been known long but is poorly documented. A case of a patient with hepatic injury following severe arsenic poisoning is reported. Histological study of the liver demonstrated acute venoocclusive disease and perisinusoidal fibrosis. This case indicates that arsenic poisoning causes veno-occlusive disease in humans. It also suggests that hepatic damage in arsenic poisoning is secondary to vascular endothelial injury and supports the hypothesis that different patterns of hepatic vascular injury might proceed from a common mechanism.     

Acute fulminant hepatitis B in a patient with diabetic nephropathy treated successfully with concomitant lamivudine and molecular adsorbents recirculating system

A 36-year-old man with type 2 diabetes and diabetic nephropathy treated with hemodialysis developed hepatitis B virus (HBV)-induced acute fulminant hepatic failure (FHF). Despite supportive treatment, the condition rapidly progressed as manifested by severe jaundice, coagulopathy and hepatic coma. He was placed on the waiting list for liver transplantation and was treated with lamivudine and extracoporeal liver support with the molecular adsorbent recirculating system (MARS). After three 8-h sessions of MARS treatment in 1 week, he had remarkable improvement in clinical symptoms and serum biochemistry. On the 14th hospital day, surface antigen seroconversion was noted with undetectable hepatitis B virus surface antigen (HBs Ag) and low titre of anti-HBs antibody, indicating a complete recovery from acute fulminant hepatitis B. MARS treatment has been reported to benefit patients with liver failure from different causes including acute exacerbation of chronic hepatitis B, poisoning, post transplantation and Wilson's disease. The present case suggests its potential benefit when combined with lamivudine in treating uremic patients with acute fulminant hepatitis B.     

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology

Background/Aims: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure.Methods: The 5′-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12).Results: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25%, and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure.Conclusions: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.