What is the treatment for Drug-Induced Liver Injury (DILI)?

Treatment for Drug-Induced Liver Injury (DILI)

The primary treatment for drug-induced liver injury is immediate discontinuation of the suspected offending drug, which is the most effective intervention to prevent progression to severe liver injury or failure. 1

Initial Management

1. Drug Discontinuation:

   • Promptly stop the suspected causative agent upon suspicion of DILI
   • Avoid re-exposure to the same drug, as this can trigger more severe reactions

2. Assessment of Severity:

   • Monitor liver biochemistry tests (ALT, AST, ALP, GGT, total and direct bilirubin)
   • Evaluate for signs of hepatic decompensation (encephalopathy, coagulopathy, ascites)
   • Repeat blood tests within 2-5 days for hepatocellular DILI or 7-10 days for cholestatic DILI 2

3. Exclusion of Alternative Causes:

   • Rule out viral hepatitis, autoimmune hepatitis, biliary obstruction, alcoholic liver disease
   • Consider imaging to exclude biliary obstruction or malignancy

Specific Treatments

N-acetylcysteine (NAC)

• Indicated for: Acetaminophen (paracetamol) overdose (intrinsic DILI)
• Evidence: Empirically used but not substantiated by randomized controlled trials for idiosyncratic DILI 1

Corticosteroids

• Indicated for: Selected cases with autoimmune features or immune-mediated DILI
• Candidates who may benefit:
  • DILI with prominent immune or hypersensitivity features
  • DILI caused by immune checkpoint inhibitors
  • DILI with autoimmune-like presentation
• Evidence: Controversial with mixed results; no definitive RCTs supporting routine use 3

Ursodeoxycholic Acid

• Indicated for: Cholestatic pattern of DILI
• Evidence: May benefit some patients with cholestatic DILI, but limited robust evidence 1

Management Based on DILI Pattern and Severity

Mild to Moderate DILI

• Discontinue offending drug
• Supportive care
• Monitor liver tests until resolution
• Avoid hepatotoxic medications

Severe DILI

• Discontinue offending drug
• Close monitoring of liver function
• Consider hospitalization
• Early referral to a liver specialist if:
  • ALT ≥5× baseline or ≥500 U/L
  • ALT ≥3× ULN with total bilirubin ≥2× ULN (Hy's Law criteria)
  • Any signs of hepatic decompensation 2

DILI with Acute Liver Failure

• Immediate referral to a liver transplant center
• Intensive supportive care
• Evaluation for liver transplantation
• Particularly important for non-acetaminophen DILI with signs of liver failure 4

Special Considerations

DILI in Patients with Pre-existing Liver Disease

• Lower thresholds for drug discontinuation
• For patients with elevated baseline ALT:
  • Consider drug discontinuation when ALT reaches 5× baseline or 500 U/L (whichever occurs first)
  • If ALT ≥2× baseline with total bilirubin ≥2× ULN, discontinue drug 2

DILI from Tuberculosis Medications

• For mild DILI: Consider regimens with fewer hepatotoxic agents
• Alternative regimens include:
  1. Treatment without PZA: INH, RIF, and EMB for 2 months, followed by 7 months of INH and RIF
  2. Treatment without INH and PZA: RIF and EMB with a fluoroquinolone for 12-18 months
  3. Treatment without INH: RIF, PZA, and EMB with or without a fluoroquinolone for at least 6 months
  4. For severe liver disease: EMB with a fluoroquinolone, cycloserine, and injectable for 18-24 months 2

Monitoring and Follow-up

• Frequency of monitoring depends on DILI pattern and severity
• Hepatocellular DILI: Repeat tests within 2-5 days
• Cholestatic DILI: Repeat tests within 7-10 days 2
• Continue monitoring until liver tests normalize or return to baseline
• Document the causative agent to prevent future re-exposure

Rechallenge Considerations

• Generally not recommended for severe DILI cases
• Contraindications to rechallenge:
  • Previous Hy's Law criteria fulfillment
  • Signs of hepatic decompensation
  • Hypersensitivity features (rash, fever, eosinophilia)
  • Underlying advanced liver disease 2

Prevention Strategies

• Increased vigilance with known hepatotoxic medications
• Dose adjustment in patients with pre-existing liver disease
• Regular monitoring of liver enzymes for high-risk medications
• Patient education about signs and symptoms of liver injury
• Avoidance of alcohol and other hepatotoxic substances while taking potentially hepatotoxic medications

Remember that early recognition and prompt discontinuation of the offending drug remain the cornerstone of DILI management, as there are no specific antidotes for most forms of idiosyncratic DILI.