MARS: optimistic therapy method in fulminant hepatic failure secondary to cytotoxic mushroom poisoning – a case report

Abstract

Poisoning by cytotoxic mushrooms (Amanita phalloides and related species) is associated with severe morbidity and a high mortality rate (lethality > 20% in adults and > 50% in children). The main causes of this intoxication are the amatoxines, which inhibit DNA-dependent RNA Polymerase II or B. This interaction leads to a tight complex, and the inhibition is of a non-competitive type (1); in addition to those tight binding inhibitors of adenosine kinase, papain, cathepsin L, cathepsin B, cysteine proteinase and bromelain (2), inhibit the synthesis of messenger RNA in the hepatocytes, decrease the formation of coagulation factors and of immunoglobulins and effect a vasoconstriction. They also have an influence on the transcription and lesions that are seen in cells with rapid protein synthesis, particularly in liver and renal cells, with the cellular changes causing the fragmentation and segregation of all nuclear components, even at low toxin concentrations (3). Phallotoxin, which is the other toxin isolated from death cap, binds with a high affinity to microfilamentous structures - in particular, to F-actin, which stimulates the polymerization of G-actin, stabilizes the F-actin filaments, irreversibly polymerizes actin filaments and causes cholestasis (4). Liver is recognized as the target organ for Amanita phalloides toxins; it is presented by fatty degeneration, acute toxic dystrophy and centrilobular necroses (5). Therapeutic options employed to treat mushroom intoxication, such as hemodiaperfusion on activated charcoal, high dosages of penicillin G, oral charcoal, etc., very often failed to act properly and liver transplantation (when a graft is available) appeared to be the only solution. The most polarized debate concerns the value of extracorporeal elimination. Plasmapheresis and peritoneal dialysis proved much less useful for this purpose; neither haemodialysis (HD) nor haemoperfusion (HP) contributed to the clearance of amatoxin (6, 7). Recently, Stange et al. (8). introduced a new detoxication method (referred to as MARS) for protein-bound substances in patients with liver failure and grade III and IV hepatic encephalopathy. MARS was performed with an albumin-containing dialysate, which is recycled in a closed loop that contains a charcoal cartridge, an anion exchanger resin adsorber and a conventional haemodialyser. With dialysis using an albumin-containing dialysate, protein-bound substances, which are usually not sufficiently dialysable, can be eliminated. The treatments increase the rate of toxin elimination to the extent that the toxic exposure of highly susceptible cells, such as hepatocytes, is minimized. This leads to the surprise recovery of the poisoning patient, despite her severe condition, even as late as up to a week after mushroom ingestion.

Mycetism: A Review of the Recent Literature

“…Fulminant hepatic failure is characteristic of severe toxicity. Liver pathology is characterized by fatty degeneration and centrilobular necrosis [84,90,94,96]. Acute tubular necrosis, with damage to the proximal tubules, can also be seen [84,85].…”

“…Acute tubular necrosis, with damage to the proximal tubules, can also be seen [84,85]. Death, when it occurs, is generally at 4-16 days but may occur later [6,83,84,89,94,[96][97][98][99][100][101]. Less severely poisoned patients may recover, rather than progress to fulminant hepatic failure [84].…”

“…Similarly, some report that plasmapheresis reduces mortality [26,99,118]; others doubt its efficacy [8,32,33]. Liver albumin dialysis [molecular absorbent recirculating system (MARS) or fractionated plasma separation and adsorption with high-flux dialysis (Prometheus)] has been successfully utilized, while awaiting liver transplantation; however, patients may die awaiting organ donation [3,25,31,37,38,83,90,94,[119][120][121].…”

Experience of Treatments of Amanita Phalloides-induced Fulminant Liver Failure with Molecular Adsorbent Recirculating System and Therapeutic Plasma Exchange

“…Several studies have suggested that early hemoperfusion (<24 hours after exposure) over a charcoal filter is effective in averting the deleterious effects of amatoxins and should be considered (16). Hemodialysis may also be used; however, because of the rapid time course of the absorption and excretion of amatoxins, hemodialysis will have a limited effect, even if applied 24 hours after consumption (17)(18). MARS is a modified dialytic method that mimics the biological features of the hepatocyte membrane.…”

The Effects of N-acetylcysteine in Patients with Amanita phalloides Intoxication

“…The most efficient procedures are hemoperfusion and plasmapheresis. High-dose penicillin and silibinin are used to block toxins from gaining access to hepatocytes [4,[11][12][13][14][15]. Silibinin is also used for damaged liver cell regeneration.…”