Core concept1 exam ›
- Complementary medicines are pharmacologically active but regulated as listed, not registered, products in Australia - no efficacy assessment, and batch-to-batch variability
- Injury patterns mirror conventional DILI
- Direct/intrinsic - dose-related (pyrrolizidine alkaloids)
- Idiosyncratic - hepatocellular, cholestatic or mixed
- Contamination and adulteration - heavy metals, undeclared conventional drugs (NSAIDs, steroids, sibutramine)
Key detail
| Agent | Pattern |
|---|---|
| Kava (Piper methysticum) | Severe hepatitis, acute liver failure - restricted or banned in several countries |
| Comfrey, bush teas, heliotropium | Pyrrolizidine alkaloids -> hepatic sinusoidal obstruction syndrome (veno-occlusive disease) |
| Black cohosh | Hepatocellular, autoimmune-like hepatitis |
| Germander (Teucrium) | Acute and chronic hepatitis |
| Chaparral | Hepatocellular necrosis, cholestasis |
| Green tea extract (high-dose catechins) | Acute hepatocellular injury |
| Anabolic androgenic steroids in "bodybuilding" supplements | Bland cholestasis, prolonged jaundice |
| Herbalife, Hydroxycut, OxyELITE Pro (multi-ingredient) | Acute hepatitis, ALF |
| Amanita phalloides (amatoxin) | Fulminant hepatic failure |
| Ma huang (ephedra), aristolochic acid | Hepatitis; aristolochic acid also causes nephropathy and urothelial cancer |
- St John's wort is not primarily hepatotoxic - it is the great interaction offender
- Potent CYP3A4 and P-gp inducer -> loss of efficacy of the oral contraceptive, ciclosporin, tacrolimus, warfarin, DOACs, HIV antiretrovirals, and it is serotonergic
- RUCAM score is the structured causality assessment tool for suspected DILI
- Diagnosis is one of exclusion - viral serology (A, B, C, E, EBV, CMV), autoimmune markers, imaging, and a careful temporal history
- Latency is typically weeks to months and injury may progress for weeks after cessation
Clinical relevance
- Ask specifically about supplements, herbal medicines, teas, protein powders and "natural" remedies in every case of unexplained LFT derangement - patients do not consider them medicines and will not volunteer them
- Multi-ingredient nutritional supplements are now a leading cause of drug-induced acute liver failure in Western series
- Management: stop everything non-essential, supportive care, monitor INR and encephalopathy, early transplant unit referral if INR rising or encephalopathy develops
- Hy's law predicts poor outcome: ALT >3x ULN with bilirubin >2x ULN and no biliary obstruction -> ~10% mortality
- Report to the TGA - post-marketing reporting is the only surveillance mechanism for listed products
- Warn transplant recipients and patients on warfarin, DOACs or antiretrovirals explicitly about St John's wort
Correlations1 exam ›
- Drug metabolism adjustments in liver failure
- CYP450-mediated drug interactions - St John's wort as an inducer
- Acute liver failure; King's College criteria
- Sinusoidal obstruction syndrome after stem cell transplant
- N-acetylcysteine in paracetamol toxicity
4 of 4 sections written · drafted 2026-09-04