Conditions · Gastroenterology and hepatology
Drug-induced liver injury !
Liver damage caused by a medicine, herbal product or supplement. It can look like hepatitis or blocked bile and usually improves when the cause is stopped.
Updated 2026-11-01
Structures involved
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Why it happens
- Chemical (toxic) cell injury: direct and after metabolism
- Injury by therapeutic drugs: the classic examples
- Cytochrome P450 system
- Acetaminophen metabolism and NAPQI
- Glutathione (GSH)
- Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells
What it is
Liver injury caused by prescription or over-the-counter medicines, herbal remedies or dietary supplements. It can mimic almost any liver disease, from mild enzyme rises to cholestasis or acute liver failure. Paracetamol (acetaminophen) overdose is the classic dose-dependent form; most other cases are idiosyncratic.
Who gets it
A leading cause of acute liver failure in many countries. In Latin America, antituberculosis drugs, antibiotics (amoxicillin-clavulanate), non-steroidal anti-inflammatories and herbal and weight-loss products are common culprits; the Latin American DILI network collects such cases.
Causes
- Intrinsic (predictable, dose-dependent): paracetamol overdose
- Idiosyncratic (unpredictable, not dose-related): amoxicillin-clavulanate, isoniazid and other antituberculosis drugs, nitrofurantoin, valproate, phenytoin, methotrexate, amiodarone, statins
- Herbal and dietary supplements, including anabolic steroids and weight-loss products
- Immune-mediated injury, sometimes with rash and eosinophilia (DRESS)
Risk factors
- Alcohol use and malnutrition (paracetamol, isoniazid)
- Older age (isoniazid, amoxicillin-clavulanate) and female sex for some drugs
- Pre-existing liver disease, HIV or viral hepatitis
- Genetic variants (slow acetylators, HLA types)
- Several hepatotoxic drugs at once
Pathophysiology
The drug or a reactive metabolite, often formed by cytochrome P450 enzymes, damages hepatocytes directly or triggers an immune response. In paracetamol overdose glutathione is depleted and the toxic metabolite NAPQI causes centrilobular necrosis. Injury may target hepatocytes (hepatocellular), bile flow (cholestatic) or both (mixed).
Classification
- Hepatocellular: ALT rise predominant (R ratio ≥5)
- Cholestatic: ALP rise predominant (R ≤2)
- Mixed (R between 2 and 5)
- Intrinsic versus idiosyncratic
Symptoms and signs
- Often none; only raised liver enzymes on monitoring
- Fatigue, nausea, loss of appetite and right upper abdominal discomfort
- Jaundice and dark urine
- Itching and pale stools in cholestatic forms
- Fever, rash and eosinophilia in hypersensitivity reactions
Diagnosis
- Clinical
- A diagnosis of exclusion: a detailed timeline of every medicine, herbal product and supplement taken in the past months, with onset of injury typically days to months after starting. Improvement after withdrawal (dechallenge) supports the diagnosis; scoring systems such as RUCAM estimate causality.
- Tests
- ALT, AST, ALP, bilirubin, INR and albumin; the R ratio defines the pattern. Exclude viral hepatitis (A, B, C, E), autoimmune hepatitis, alcohol and other causes. Paracetamol level when overdose is possible. Eosinophil count. Biopsy only in unclear cases.
- Imaging
- Ultrasound to exclude biliary obstruction, focal lesions and vascular causes such as Budd-Chiari; MRCP in cholestatic injury when obstruction is still possible.
Differential diagnosis
- Acute viral hepatitis
- Autoimmune hepatitis
- Alcohol-related hepatitis
- Biliary obstruction (choledocholithiasis, tumour)
- Ischaemic hepatitis and Budd-Chiari syndrome
Goal of treatment
Identify and stop the culprit agent early, give a specific antidote when one exists, recognise acute liver failure in time, and prevent re-exposure.
Treatment
- Acute
- Stopping the suspected drug or product is the key measure. Paracetamol overdose is treated urgently with N-acetylcysteine; severe cases with encephalopathy or coagulopathy need intensive care.
- Medical
- Supportive care and symptom relief; corticosteroids are considered in hypersensitivity or autoimmune-like injury; L-carnitine for valproate toxicity. Antituberculosis regimens are reintroduced stepwise under specialist guidance.
- Follow-up
- Baseline and periodic liver tests for drugs with known risk (isoniazid, methotrexate, some antiretrovirals); nursing education on early symptoms; INR, glucose and mental status in severe cases.
- Surgical
- Urgent liver transplantation in acute liver failure that meets transplant criteria.
Complications
- Acute liver failure
- Prolonged cholestasis and vanishing bile duct syndrome
- Chronic liver injury and fibrosis with continued exposure
- Severe skin reactions (DRESS, Stevens-Johnson syndrome) in hypersensitivity forms
Prognosis
Most patients recover within weeks to months after the drug is stopped. Jaundice with hepatocellular injury carries roughly a 10% risk of death or transplant (Hy's law). Re-exposure to the same drug may cause faster and more severe injury.
Prevention
- Checking liver tests before and during treatment with high-risk drugs
- Avoiding unnecessary combinations of hepatotoxic drugs and alcohol
- Asking about herbal products and supplements in every drug history
- Recording the culprit as an allergy to avoid re-exposure
Test yourself
Think of the answer, then tap the question to see it.
What is Hy's law in drug-induced liver injury?
Hepatocellular injury (ALT >3× normal) with jaundice (bilirubin >2× normal) without another cause; it predicts about 10% mortality or transplant.
How is the pattern of DILI classified?
By the R ratio (ALT/ULN ÷ ALP/ULN): ≥5 hepatocellular, ≤2 cholestatic, between 2 and 5 mixed.
Which antituberculosis drugs are classically hepatotoxic?
Isoniazid, rifampicin and pyrazinamide.
What is the single most important step in managing suspected DILI?
Stopping the suspected drug, herbal product or supplement.
What is the antidote for paracetamol (acetaminophen) hepatotoxicity?
N-acetylcysteine, which replenishes glutathione.
Related conditions
- Acetaminophen toxicity
- Acute liver failure
- Viral hepatitis
- Autoimmune hepatitis
- Alcoholic liver disease (biochemistry)
- Tuberculosis
- Cutaneous drug reactions and DRESS
- Budd-Chiari syndrome
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Drug-induced liver injury: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2024).
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