Drug-Induced Liver Injury (DILI)
liver damage caused by prescription medications, over-the-counter drugs, herbal products, or dietary supplements. It is one of the most common causes of acute liver failure worldwide and can mimic almost any type of liver disease. DILI can be intrinsic (predictable), where liver injury is dose-dependent and occurs in most people exposed to a toxic dose (e.g., acetaminophen overdose), or idiosyncratic (unpredictable), which occurs in susceptible individuals without clear dose dependency. The severity ranges from mild, reversible enzyme elevations to acute liver failure requiring transplant.
Symptoms
The symptoms of DILI vary widely and can resemble viral hepatitis or autoimmune liver disease. Common presentations include:
- Fatigue and weakness
- Loss of appetite, nausea, or vomiting
- Abdominal pain (especially in the upper right quadrant)
- Dark urine and pale stools
- Jaundice (yellowing of the skin and eyes)
- Itching (pruritus)
- Fever, rash, or joint pain (in some drug reactions with immune features)
- In severe cases: confusion, easy bruising/bleeding, swelling of legs/abdomen, or sudden liver failure.
Causes
- Prescription drugs:
- Acetaminophen (in overdose – most common intrinsic cause)
- Antibiotics (e.g., amoxicillin-clavulanate, isoniazid, nitrofurantoin, minocycline)
- Antiepileptics (valproate, phenytoin, carbamazepine)
- Statins, methotrexate, amiodarone, etc.
- Over-the-counter (OTC) medications:
- Excessive acetaminophen
- NSAIDs like diclofenac or ibuprofen (rare but possible)
- Herbal and dietary supplements:
- Green tea extract
- Kava
- Anabolic steroids
- Certain weight-loss or bodybuilding supplements
- Risk factors:
- Advanced age
- Female sex
- Alcohol use
- Pre-existing liver disease
- Genetic predisposition
- Polypharmacy (taking multiple drugs)
Diagnosis
There is no single test for DILI, so diagnosis relies on careful evaluation:
- No single test for DILI — diagnosis relies on careful evaluation:
- Medical history: Reviewing all drugs, supplements, and herbs taken in the weeks to months before symptoms.
- Blood tests: Elevated liver enzymes (ALT, AST, ALP), bilirubin, INR; different patterns suggest hepatocellular, cholestatic, or mixed injury.
- Exclusion of other causes: Viral hepatitis (A, B, C, E), autoimmune hepatitis, alcohol-related injury, metabolic diseases.
- Scoring systems: RUCAM (Roussel Uclaf Causality Assessment Method) helps assess the likelihood of DILI.
- Imaging: Ultrasound, CT, or MRI to rule out biliary obstruction or other liver disease.
- Liver biopsy: Sometimes performed when diagnosis is uncertain; may show characteristic patterns (e.g., hepatitis-like, cholestatic, or mixed injury).
Treatment
- The cornerstone of treatment is identifying and stopping the offending drug. Additional steps include:
- Immediate discontinuation: Stop the suspected medication/supplement.
- Supportive care: Hydration, rest, and monitoring liver function.
- Specific antidotes:
- N-acetylcysteine (NAC) for acetaminophen overdose (life-saving if given early).
- Corticosteroids may be considered if an autoimmune-like reaction is suspected.
- Avoidance: No alcohol or hepatotoxic agents during recovery.
- Hospitalization: For severe cases with jaundice, coagulopathy, or encephalopathy.
- Liver transplant: Required in cases of acute liver failure unresponsive to medical therapy.
FAQs
Yes, almost any drug has the potential to cause liver injury, but some are far more common culprits than others.
It can appear within days (e.g., acetaminophen overdose) or weeks to months later with idiosyncratic reactions.
Most cases resolve once the offending drug is stopped, but severe cases may cause permanent damage or liver failure.
People with existing liver disease, the elderly, women, those taking multiple medications, and people consuming alcohol heavily.
Yes. Herbal and dietary supplements (especially unregulated products for weight loss, bodybuilding, or sexual enhancement) are increasingly recognized causes of DILI.