Elimination Capacity Determines Outcome in Amatoxin Mushroom Poisoning-Induced Acute Liver Failure: A Globally Applicable Management Framework

ABSTRACT Amatoxin mushroom poisoning causes acute liver failure; progression from cholera-like hypovolemia resolution to fatal multisystem collapse occurs unpredictably. We conducted a prospective single-arm multicenter trial (N=99) investigating proactive toxicokinetic-based management: sustained hydration for renal protection and clearance preservation, fasting plus octreotide to arrest enterohepatic circulation, and intravenous silibinin to block hepatic reuptake. Transplant-free recovery: 98.8% among protocol-adherent patients (n=86). Multivariable analysis: sustained hydration (P<0.001) and silibinin (P=0.003) predicted survival; octreotide reduced coagulopathy recovery time (P=0.01); N-acetylcysteine and charcoal achieved neither. Conventional MELD score–outcome relationships vanished in protocol-adherent patients, suggesting management modified the natural history. Poor outcomes followed a reproducible sequence—hydration withdrawal, lactate rebound, oliguric nephropathy, multisystem failure—kidney failure, not liver, precipitated collapse. These findings establish renal clearance preservation and gallbladder sequestration as central outcome determinants, supporting a globally applicable management framework substituting gallbladder drainage when silibinin is unavailable or likely to fail. ClinicalTrials.gov identifier: NCT00915681 .