What is the treatment for liver injury using N-acetylcysteine (NAC)?

N-acetylcysteine (NAC) Treatment for Liver Injury

N-acetylcysteine (NAC) is the definitive treatment for acetaminophen-induced liver injury and should be administered immediately when acetaminophen toxicity is suspected, without waiting for serum acetaminophen determinations. 1

Indications for NAC Treatment

• Acetaminophen overdose: Primary indication for NAC therapy
  • Acute single ingestion with toxic serum levels
  • Repeated supratherapeutic ingestions (RSI)
  • Unknown time or amount of ingestion with suspicion of toxicity 2
• Non-acetaminophen liver failure: May improve outcomes in early-stage encephalopathy (grades I-II) 1

Assessment and Treatment Decision

1. For acute acetaminophen ingestion:

   • Obtain acetaminophen concentration at least 4 hours post-ingestion
   • Use Rumack-Matthew nomogram to determine risk:
     • ≥200 mg/L at 4 hours: Probable toxicity
     • 100-200 mg/L at 4 hours: Possible toxicity
     • <100 mg/L at 4 hours: No risk 1

2. Treatment timing:

   • Critical treatment window: 0-8 hours post-ingestion
   • Efficacy diminishes after 8 hours but should still be administered
   • Treatment between 15-24 hours has limited efficacy but should not be withheld 2

NAC Administration Protocols

Intravenous Protocol

• Loading dose: 150 mg/kg over 15-60 minutes
• First maintenance dose: 50 mg/kg over 4 hours
• Second maintenance dose: 100 mg/kg over 16 hours
• Total duration: 21 hours 1

Oral Protocol

• Loading dose: 140 mg/kg (diluted to 5% solution)
• Maintenance dose: 70 mg/kg every 4 hours for 17 doses
• Total duration: 72 hours 1

Alternative IV Protocol (48-hour)

• Loading dose: 140 mg/kg
• Maintenance dose: 70 mg/kg every 4 hours for 12 doses
• Shows low hepatotoxicity rates and few adverse events 3

Treatment Duration Considerations

• The 21-hour IV protocol is often too short for optimal protection
• The full 72-hour oral course is frequently unnecessary 4
• Treatment should continue until:
  • Clinical improvement occurs
  • Normalization of liver enzymes
  • Resolution of acidosis and organ dysfunction 1

Monitoring During Treatment

1. Laboratory parameters:

   • Liver function tests (AST, ALT, bilirubin, INR)
   • Renal function (creatinine, BUN)
   • Blood glucose and electrolytes
   • Acid-base status 2

2. Adverse reactions (occur in 10-15% of patients):

   • Nausea and vomiting (most common)
   • Flushing
   • Urticaria or bronchospasm (rare)
   • Anaphylactic reactions (manage with antihistamines and epinephrine if necessary) 1

Efficacy and Outcomes

• NAC prevents hepatic injury when administered early after acetaminophen overdose
• Treatment within 8 hours of ingestion results in hepatotoxicity rates as low as 3.4% 3
• Mortality rates vary from 0-52% depending on timing of treatment 5
• NAC improves outcomes by:
  1. Scavenging reactive metabolites (N-acetyl-p-benzoquinone imine)
  2. Enhancing hepatic and mitochondrial glutathione levels
  3. Supporting mitochondrial energy metabolism 6

Special Considerations

• NAC may be beneficial in non-acetaminophen liver injury, including drug-induced liver injury from other medications 7
• Higher doses of NAC may be necessary for very large overdoses 3
• If no response after approximately 1 week of therapy, consider hepatic transplantation 1
• In cases with persistent severe coagulopathy or encephalopathy, transplantation considerations may need to begin after 2-3 days 1

Pitfalls and Caveats

• Patient-reported acetaminophen ingestion history is often inaccurate
• Acetaminophen concentrations obtained earlier than 4 hours post-ingestion may be misleading
• Current treatment nomograms may underestimate risk for patients presenting within 8 hours of ingestion 4
• Delaying treatment beyond 8 hours significantly increases risk of hepatotoxicity and mortality 5