Drug-Induced Liver Disorders (DILI) occur when certain medications, herbal products, or chemicals damage the liver. The liver is responsible for metabolizing most drugs, so it is highly vulnerable to toxicity. DILI can range from mild elevation of liver enzymes to severe hepatitis, liver failure, or even death. Early detection and discontinuation of the offending drug are critical to preventing complications.
1. Types of Drug-Induced Liver Injury
1. Intrinsic (Predictable) Liver Injury
- Occurs in a dose-dependent manner
- Predictable and reproducible
- Example: Acetaminophen overdose
2. Idiosyncratic (Unpredictable) Liver Injury
- Not dose-related
- Occurs in a small number of patients
- Immune or metabolic mechanisms involved
- Examples: Isoniazid, amoxicillin–clavulanate
2. Common Hepatotoxic Drugs
Analgesics and Antipyretics
- Acetaminophen (most common cause of acute liver failure)
Antibiotics
- Isoniazid
- Rifampicin
- Amoxicillin–clavulanate
- Tetracyclines
Anticonvulsants
- Valproic acid
- Phenytoin
- Carbamazepine
Cardiovascular Drugs
- Statins
- Amiodarone
Antifungal and Antiviral Agents
- Ketoconazole
- Nevirapine
Herbal and Dietary Supplements
- Green tea extracts
- Kava
- Ayurvedic preparations (in certain cases)
3. Symptoms of Drug-Induced Liver Disorders
General Symptoms
- Nausea and vomiting
- Loss of appetite
- Fatigue and weakness
- Abdominal pain (particularly in the right upper quadrant)
Hepatic Symptoms
- Jaundice
- Dark urine
- Pale stools
- Itching
Severe Symptoms
- Confusion (hepatic encephalopathy)
- Bleeding tendencies
- Ascites
4. Diagnosis of DILI
DILI is diagnosed by excluding other causes of liver injury and identifying temporal relation with drug intake.
- Liver function tests: Elevated ALT, AST, ALP, bilirubin
- History of drug exposure: Timing is crucial
- Rule out viral hepatitis: HAV, HBV, HCV tests
- Imaging: Ultrasound/CT to exclude obstruction
- RUCAM scoring: Used for causality assessment
5. Management of Drug-Induced Liver Disorders
1. Stop the Offending Drug Immediately
This is the most important step in management.
2. Supportive Care
- Hydration
- Rest
- Nutritional support
3. Antidotes
- N-acetylcysteine (NAC) for acetaminophen toxicity
4. Manage Complications
- Treat coagulopathy
- Treat encephalopathy
- Monitor for renal impairment
5. Hospitalization
Needed for severe hepatic injury, especially with high bilirubin or INR.
6. Liver Transplantation
Indicated in acute liver failure when patient does not respond to medical therapy.
6. Prevention of DILI
- Use the lowest effective dose of drugs
- Avoid unnecessary polypharmacy
- Monitor liver enzymes during high-risk treatments
- Avoid alcohol during hepatotoxic drug therapy
- Educate patients about warning signs
7. Role of the Pharmacist
- Identify high-risk medications and patient factors
- Educate patients on early symptoms of liver injury
- Monitor drug interactions and cumulative toxicity
- Review liver function tests during therapy
- Prevent overdose of drugs like acetaminophen
- Guide patients to avoid alcohol during treatment
- Report DILI cases to pharmacovigilance centers
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