Acute liver failure after amanitin poisoning: a porcine model to detect prognostic markers for liver regeneration.

Abstract

Over 90% of fatal mushroom poisoning occurs after ingestion of amanitin-containing species. This study aimed to investigate markers indicating spontaneous liver regeneration in a porcine acute liver failure (ALF) model after α-amanitin intoxication. German landrace pigs received either 0.15mg/kg (n=5) α-amanitin intravenously or 0.35mg/kg (n=5) intraportally. Pigs were invasively monitored and kept under general anesthesia throughout the experiment. Laboratory parameters were analyzed every 8h. ALF occurred in all animals (10/10) 41±3h after intoxication. All pigs receiving 0.35mg/kg α-amanitin and one pig receiving 0.15mg/kg α-amanitin died 57±16h after the primary onset of ALF. Four pigs of the 0.15mg/kg intoxication group recovered spontaneously from ALF after 56±6h. Starting at 32h after intoxication, significantly higher values of albumin and total plasma protein could be measured in surviving animals (p<0.05). A significant temporary increase in the tumor necrosis factor alpha (TNF-α) plasma concentration was detected 40-80h after intoxication in recovering animals (p<0.05). This porcine model represents a novel tool to analyse multiple aspects of liver regeneration following α-amanitin poisoning to allow early discrimination between a fatal course and survivors. Decreased albumin and total plasma protein concentrations in the early intoxication phase indicated a lethal outcome, while an increase in the TNF-α plasma concentration was identified as the earliest prognostic plasma marker detecting liver regeneration a long time before liver function was biochemically and clinically impaired.