Drug- and toxin-induced liver injury
- Topic
Because the liver processes most drugs, many medicines, herbs and toxins can damage it, in patterns that mimic other liver diseases.
What it is
Drug-induced liver injury can imitate almost any liver disease. Injury is predictable and dose-dependent (acetaminophen, carbon tetrachloride, Amanita toxins) or idiosyncratic, rare and unrelated to dose, often after weeks to months of use and sometimes with features of hypersensitivity. Most injury comes from reactive metabolites made by cytochrome P450 enzymes, which are most active in zone 3. It is a leading cause of acute liver failure.
Step by step
- The drug reaches the liver and is metabolized, mostly by cytochrome P450 enzymes (densest in zone 3).
- Some metabolites are reactive and bind proteins or generate oxidative stress.
- Detoxifying systems (glutathione) are used up, especially with enzyme inducers such as alcohol or rifampicin.
- Hepatocytes die directly (predictable injury) or modified proteins trigger an immune attack (idiosyncratic injury).
- Bile transporters may be blocked, producing cholestasis.
- Stopping the drug usually allows recovery; a minority progress to chronic injury or acute liver failure.
Patterns of drug and toxin liver injury, with examples
| Pattern | Microscopy | Examples |
|---|---|---|
| Zonal necrosis (predictable) | Zone 3 coagulative necrosis with little inflammation | Acetaminophen, carbon tetrachloride, Amanita mushrooms |
| Acute hepatitis (idiosyncratic) | Lobular hepatitis like viral hepatitis | Isoniazid, phenytoin, methyldopa, immune checkpoint inhibitors |
| Bland cholestasis | Bile plugs with little inflammation | Oral contraceptives, anabolic steroids |
| Cholestatic hepatitis | Cholestasis with inflammation and duct injury | Amoxicillin-clavulanate, chlorpromazine, some antibiotics |
| Microvesicular steatosis | Foamy hepatocytes with tiny droplets | Valproate, tetracycline, aspirin in children |
| Steatohepatitis | Fat, ballooning, Mallory-Denk bodies | Amiodarone, methotrexate, tamoxifen |
| Granulomatous | Epithelioid granulomas | Sulfonamides, allopurinol |
| Vascular | Sinusoidal obstruction, peliosis, hepatic vein thrombosis | Pyrrolizidine alkaloids and chemotherapy (SOS), anabolic steroids (peliosis), oral contraceptives |
| Tumours | Adenoma, angiosarcoma | Contraceptive and anabolic steroids (adenoma); vinyl chloride, arsenic, thorotrast (angiosarcoma) |
Clinical notes
- A careful history of medicines, herbal products and supplements is the key to diagnosis.
- Combined hepatocellular injury and jaundice from a drug carries a significant risk of death (Hy's law).
Test yourself
Think of the answer, then tap the question to see it.
Why does acetaminophen overdose cause centrilobular necrosis?
CYP2E1 in zone 3 converts it to NAPQI; when glutathione is depleted NAPQI binds cell proteins and kills pericentral hepatocytes.
What is the difference between predictable and idiosyncratic hepatotoxicity?
Predictable injury is dose-dependent and occurs in anyone given enough; idiosyncratic injury is rare, not dose-related and depends on individual susceptibility.
Which drugs typically produce microvesicular steatosis?
Valproate, tetracycline and aspirin in children (Reye syndrome); they impair mitochondrial fatty acid oxidation.
Which exposures are linked to hepatic angiosarcoma?
Vinyl chloride, arsenic and the old contrast agent thorotrast.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Drug-induced liver injury: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Acetaminophen overdose: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.