Amatoxin-induced acute liver failure complicates misidentified foraged mushroom ingestion worldwide; abrupt multisystem collapse punctuates apparent improvement. Our prospective single-arm clinical trial investigated proactive toxicokinetic-based management to preserve elimination capacity: sustained enhanced hydration to maintain renal clearance; fasting plus octreotide to suppress meal-driven enterohepatic circulation; and intravenous silibinin to inhibit OATP1B3-mediated hepatic uptake, enabling safe passage and elimination of gallbladder-confined amatoxin-laden bile. Safety population (N=99) transplant-free recovery (TFR): 88.0% (87 recoveries, 6 transplants, 6 deaths). Protocol-adherent Efficacy population (n=86) TFR: 98.8% (85 recoveries, 1 transplant, 0 deaths). Multivariable analysis identified uninterrupted hydration as strongest TFR predictor (P<0.001), followed by earlier silibinin initiation (P=0.003); octreotide shortened INR recovery by 11 hours (P=0.033). These findings support a toxin elimination model in which preserved renal clearance and biliary sequestration are central recovery determinants. The kinetic balance between renal clearance and hepatic uptake governs both recovery and collapse.

Competing Interests

S.T.M. received consultancy fees from Rottapharm|Madaus, MEDA, and Mylan/Viatris. All other authors declare no competing interests.

NCT00915681

Funding

Study sponsors (Rottapharm-Madaus, Meda, and Mylan) provided investigational drug, funded shipping and provided regulatory expenses.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Human Subjects Protection

Catholic Healthcare West IRB (Santa Cruz, CA) approved the study protocol and amendments; participating hospitals obtained local IRB authorization. All participants (or parents/legal guardians for minors) provided written informed consent.

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Yes

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data supporting the findings of this study are available in the Supplementary Materials. Additional de-identified data may be made available from the corresponding author upon reasonable request and subject to applicable institutional approvals and data-use requirements.