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

Management of Drug-Induced Liver Injury (DILI)

The primary and most effective treatment for drug-induced liver injury is immediate discontinuation of the suspected causative agent. 1, 2

Initial Management Steps

1. Discontinue the suspected medication immediately

   • This is the cornerstone of DILI management and the only proven effective intervention for most cases of idiosyncratic DILI 3, 1
   • Delayed discontinuation can result in irreversible liver failure and death 3

2. Assess severity based on laboratory parameters:

   • Mild: ALT < 5× ULN
   • Moderate: ALT ≥ 5× ULN but < 8× ULN
   • Severe: ALT ≥ 8× ULN, or ALT ≥ 3× ULN with total bilirubin ≥ 2× ULN, or ALT ≥ 5× ULN with symptoms 1

3. Determine pattern of injury using R value:

   • R = (ALT/ALT ULN)/(ALP/ALP ULN)
   • Hepatocellular: R ≥ 5
   • Mixed: R > 2 but < 5
   • Cholestatic: R ≤ 2 1

Monitoring and Follow-up

• Frequent monitoring of liver tests every 2-5 days initially 1
• For patients with abnormal baseline liver tests, use multiples of baseline rather than ULN for monitoring thresholds 3, 1
• Consider referral to a hepatologist if no improvement within 1-2 weeks 1

Specific Treatments

For Acetaminophen-Induced DILI (Intrinsic DILI)

• N-acetylcysteine (NAC) is the specific antidote and should be administered as soon as possible, ideally within 24 hours of ingestion 4, 2
• NAC is the only pharmacotherapy with established efficacy for DILI, specifically for acetaminophen overdose 2

For Idiosyncratic DILI

• No proven specific pharmacotherapy exists for most cases of idiosyncratic DILI 2, 5

• For selected cases with specific presentations:

  1. Corticosteroids may be considered for:

     • DILI with autoimmune features
     • Immune checkpoint inhibitor-induced liver injury
     • Severe DILI with significant inflammation 1, 6, 7

  2. Ursodeoxycholic acid may benefit patients with cholestatic DILI 1, 2, 8

  3. Anticoagulants should be considered in patients with drug-induced hepatic sinusoidal obstruction syndrome (HSOS) and coagulopathy risks 2

Management Based on Severity

Mild to Moderate DILI

• Discontinue offending drug
• Monitor liver tests every 2-5 days initially, then weekly until resolution 1
• Supportive care for symptoms

Severe DILI

• Immediate referral to a hepatologist
• Consider hospitalization for close monitoring
• Evaluate for liver transplantation if signs of liver failure develop 1
• More intensive monitoring of coagulation parameters and mental status

Special Considerations

• For patients with pre-existing liver disease, use lower thresholds for intervention
• For patients in clinical trials with NASH or cholestatic liver disease, consider interrupting study drug if:
  • ALT ≥ 5× baseline or ≥ 500 U/L (whichever occurs first) for NASH patients 3
  • ALT ≥ 3× baseline or ≥ 300 U/L with normal bilirubin for cholestatic disease patients 3, 1
  • ALT ≥ 2× baseline or ≥ 300 U/L with elevated bilirubin (≥ 2× baseline) for cholestatic disease patients 3, 1

Common Pitfalls and Caveats

• Delayed recognition and discontinuation of the causative agent can lead to progression to liver failure
• Failure to exclude alternative causes of liver injury may lead to inappropriate management
• Premature rechallenge with the suspected agent can cause more severe injury, except in oncology settings where risk-benefit may justify rechallenge 3
• Overreliance on CTCAE grading in patients with abnormal baseline liver tests may not accurately reflect severity 1

By following this systematic approach to DILI management, focusing primarily on prompt discontinuation of the suspected agent and appropriate monitoring, clinicians can optimize outcomes for patients with this potentially serious condition.