Acute liver failure temporally associated with intensive consumption of Plantago major tea: A case report

Table 3 Etiologic evaluation of acute liver failure and limitations of retrospective causality assessment

Etiologic category	Investigation or exposure	Available result/documentation	Interpretation or limitation
Viral hepatitis	Viral hepatitis investigation	Documented as negative in the medical record	The contemporaneous medical record documented negative viral hepatitis testing; individual viral assays, numerical results, methods, and testing dates were unavailable for independent retrospective verification
Autoimmune liver disease	Autoimmune liver-disease investigation	Documented as negative in the medical record	The medical record documented a negative autoimmune liver-disease investigation; individual autoantibodies, immunoglobulin results, methods, and testing dates were unavailable for independent retrospective verification
Wilson disease	Wilson disease evaluation	Documented as investigated and excluded	Wilson disease was documented as investigated and excluded; the individual diagnostic tests, numerical results, methods, and dates were unavailable for independent retrospective verification
Hemochromatosis	Hemochromatosis evaluation	Documented as investigated and excluded	Hemochromatosis was documented as investigated and excluded; the individual diagnostic tests, numerical results, methods, and dates were unavailable for independent retrospective verification
Additional viral testing	HEV, HSV, EBV, and CMV testing	Documented as investigated/negative in the medical record	The original individual assay results, methods, and testing dates were unavailable for independent retrospective verification
Drug or toxin exposure	Acetaminophen, alcohol, illicit/recreational drugs, and other medications or supplements	Patient denied acetaminophen use, alcohol consumption, and illicit/recreational drug use; no additional medications or supplements were reported beyond omeprazole and P. major infusion	No competing exposure was identified from the documented history other than omeprazole. A serum acetaminophen concentration and formal toxicology screening results were not available for retrospective verification
Competing medication	Omeprazole	Documented exposure	The exact dose and exposure dates were unavailable; omeprazole was retained as a competing exposure
Herbal exposure	P. major infusion	Approximately 2 L/day for 15 consecutive days	This represents prepared infusion volume only. Botanical authentication, quantified botanical dose, chemical analysis, and contamination testing were not available
Rechallenge	Re-exposure to P. major	Not performed	No rechallenge occurred
Dechallenge	Biochemical course after cessation	Not interpretable	Liver transplantation occurred before biochemical recovery, preventing interpretation of a conventional dechallenge course

Causality note: A formal Roussel Uclaf Causality Assessment Method score could not be calculated reliably because mandatory elements were missing, despite the negative results from important portions of the etiologic work-up. The association with Plantago major should therefore remain presumptive and temporally based rather than definitive. CMV: Cytomegalovirus; EBV: Epstein–Barr virus; HEV: Hepatitis E virus; HSV: Herpes simplex virus; P. major: Plantago major.