Diagnosis of drug-induced liver injury

The annual incidence of drug-induced liver injury (DILI) (hepatotoxicity) is reported to be approximately 15 per 100 000 people, although it is most likely underdiagnosed.

Drug-induced liver injury can be difficult to identify because diagnosis is based largely on exclusion of other causes. There may be a long period between exposure to a drug and onset of symptoms or abnormal liver biochemistry. Key diagnostic factors are:

  • the timing of onset of symptoms or abnormal liver biochemistry in relation to starting the drug (or increasing the dose)
  • the timing of resolution in relation to stopping the drug
  • whether there was recurrence with re-exposure (although rechallenge is not recommended)
  • whether the drug is known to be hepatotoxic.

For any patient with abnormal liver biochemistry, take a detailed medication history, including prescription and over-the-counter drugs, recreational drugs, and herbal or dietary supplements the patient is taking or has taken recently. Consider whether drug interactions may be a contributory factor, including interactions with herbal and dietary supplements.

Note: For any patient with abnormal liver biochemistry, take a detailed medication history that includes prescription and over-the-counter drugs, recreational drugs, and herbal or dietary supplements.

Pharmacological risk factors for drug-induced liver injury include the dose, lipophilicity and extent of liver metabolism of a drug, and drug combinations. Liver injury may be dose related and predictable, as with paracetamol. However, patient factors (eg age, female sex, genetic predisposition, pre-existing liver damage, alcohol intake, obesity, type 2 diabetes, fasting, malnutrition) can increase the risk of liver injury, even at doses generally thought to be safe. Idiosyncratic hepatotoxicity is unpredictable and can occur at any time after exposure (or re-exposure) to a drug. Drugs can also cause liver injury via indirect effects; for example, fatty liver disease due to drug-induced weight gain (eg with risperidone) or immune-mediated liver injury associated with immune checkpoint inhibitors.

The LiverTox website describes over 1200 medications, herbal products and dietary supplements that can cause drug-induced liver injury.