Home / Glossary / Drug-induced liver injury (DILI)
Conditions

Drug-induced liver injury (DILI)

liver damage caused by drugs, supplements or toxins

Drug-induced liver injury — pills and the liver

Drug-induced liver injury (DILI) is liver damage caused by medications, supplements or herbal remedies. It is a common cause of acute cytolysis and cholestasis and the leading cause of acute liver failure.

It can be predictable (dose-dependent — the classic example is a paracetamol overdose) and idiosyncratic — a rare, unpredictable response in an individual person.

Three types of injury (the R-factor)

By what predominates on tests, three types are distinguished: hepatocellular (mainly ALT rises), cholestatic (alkaline phosphatase rises) and mixed. To separate them, the R-factor is calculated = (ALT/ULN) ÷ (ALP/ULN).

Why it is dangerous: Hy's Law

The combination of hepatocellular injury with jaundice is especially worrying: if bilirubin has risen more than twofold with a relatively normal ALP, the risk of a severe outcome (death or transplantation) reaches 10% and above. This is Hy's law.

Common culprits and what to do

The liver is most often damaged by paracetamol in overdose, amoxicillin/clavulanate, anti-tuberculosis drugs, NSAIDs, amiodarone, as well as some herbal supplements and anabolic steroids. The main action is withdrawal of the suspected drug; for paracetamol poisoning — N-acetylcysteine. A useful database is LiverTox.

Reference ranges

The type of injury is determined by the R-factor: R = (ALT / ULN) ÷ (ALP / ULN).

HepatocellularR ≥ 5 (ALT predominates)
CholestaticR ≤ 2 (ALP predominates)
Mixed2 < R < 5
Hy's law (a warning sign)a rise in ALT + bilirubin > 2× ULN with a normal ALP
Important: The R-factor is calculated at the onset of injury; the result is interpreted by a doctor.

Calculate using this marker

Calculators where Drug-induced liver injury (DILI) is used directly:

R-Factor Shows what's driving the injury — cholestasis or liver-cell death Open

Frequently asked questions

Which drugs most often harm the liver?

Most often — paracetamol in overdose, amoxicillin/clavulanate, anti-tuberculosis drugs, NSAIDs, amiodarone, as well as some dietary supplements, herbal products and anabolic steroids.

Does drug-induced liver injury go away?

Usually, after the drug is withdrawn, liver function recovers. But severe forms, especially those that fall under Hy's law, are dangerous and require urgent care.

Related terms

Cytolysis (hepatocellular injury) the destruction of liver cells with release of enzymes into the blood Cholestasis the stasis of bile due to impaired outflow ALT (alanine aminotransferase) A liver enzyme; a marker of liver-cell damage AST (aspartate aminotransferase) An enzyme of the liver, heart and muscles; a marker of tissue damage Bilirubin A bile pigment; it rises when liver function is impaired Alkaline phosphatase (ALP) an enzyme of the bile ducts and bones, a marker of cholestasis GGT (Gamma-glutamyl transferase) A liver enzyme — the most sensitive marker of cholestasis and alcohol-related damage

Sources

  1. MSD Manual Professional — Liver Injury Caused by Drugs
  2. LiverTox (NCBI Bookshelf) — Drug-Induced Liver Injury
  3. FDA — Drug-Induced Liver Injury: Premarketing Clinical Evaluation
info
This content is educational and does not replace consultation with a physician. Reference ranges may vary depending on the laboratory and method — rely on the ranges stated on your own test report.
← All glossary terms