Liver transplantation represents the optimal treatment for fulminant hepatic failure from amanita phalloides poisoning

Abstract

Amanita phalloides (AP) mushrooms poisoning is a rare but serious occurrence. The main causes of this intoxication are the amatoxines, which inhibit DNA-dependent RNA polymerase II or B. The typical liver and kidney alterations of AP poisoning, consisting of massive hepatic central lobular cell necrosis and acute tubular necrosis of the kidney, are well known [1]. Recognizing the phalloides syndrome allows the institution of effective treatment to avoid possibly fatal complications. The overall prognosis for patients with fulminant hepatic failure (FHF) is poor without transplantation, with survival rates usually reported between 10% and 30% [2]. Medical treatment can prevent complications such as infections and cerebral oedema, which are the most common causes of death. Therapeutic options employed to treat mushroom intoxication include: haemodiaperfusion on activate charcoal, high dosages of penicillin G, oral charcoal, Molecular Adsorbent Recycling System (MARS) and N-acetyl cysteine infusion. When all of them fail, liver transplantation (LT) is the only option [3].When liver dysfunction occurs, transferring the patients to a liver transplant center is crucial to identify appropriate candidates for emergency LT. Indications for LT primarily include medically untreatable and markedly prolonged prothrombin time (PTT), and a constellation of findings such a metabolic acidosis, hypoglycaemia, hypofibrinogenemia and increased serum ammonia, following high serum aminotransferase levels [4]. Between May 1986 and October 2005, 515 LT procedures were performed at our Institution in Genoa. Of these, 32 adult patients underwent first LT to treat FHF. The indication for emergency LT was made according to Kings’ College Hospital criteria [5]. During the same period, 21 patients with acute AP poisoning were treated in our dedicated intensive care unit. Six of them developed irreversible signs of poisoning, FHF and were transplanted. Fifteen patients were successfully managed without LT by intensive care medical treatment with N-acetyl cysteine infusion and high dosages of penicillin G. Furthermore, among these, three of them required MARS and two haemodiaperfusion on activate charcoal. In all these patients, the amatoxines serum level was below the lethal concentration (LC) [6]. Six LT patients had an amatoxines serum level above the LC and therefore their outcome should have been fatal without LT. The findings and course of this series of patients, which is the largest reported, was analysed and prognostic criteria defined on the basis of this experience and available data. The prognosis of these six transplanted patients was assessed by monitoring liver function tests (PTT, INR, V factor, AT III, total and split bilirubin, transaminases, WBC and platelet count, serum ammonia, blood and urinary alpha-amanitin, ascites output) plus serum creatinine level as renal failure from amatoxines is often described. AP poisoning differs from other causes of acute liver failure in several respects. The following criteria suggests how to identify a lethal from a non-lethal course: PTT <20% over the course of several days, serum creatinine concentration >1.5 mg%– raising despite careful adjustment of water and electrolyte abnormalities, serum bilirubin >5 mg %, also progressive encephalopathy and or coma indicate a lethal course [5]. In our series of transplanted patients a PTT value <20% (range: 3–17%) was observed, conversely, PTT time value >20% (range: 23–41%) was found in patients successfully treated with a conservative medical approach. The whole group of transplanted patients survived. Medium follow-up is 52 months (range: 3–122 months). LT is the procedure of choice for the treatment of acute AP poisoning complicated by FHF. The identification of correct inclusion criteria for a lethal prognosis under conservative treatment is a key point. This should be taken into account when poisoned patients are to be transferred to a transplant centre for appropriate treatment. In conclusion, based on our series of patients, we believe that the key of success is represented by many factors, including immediate organ availability for LT and careful selection of patients eligible for emergency transplantation.