Referral Criteria for Liver Transplantation in Acetaminophen Toxicity
Patients with acetaminophen toxicity should be referred for liver transplantation when they meet the King's College criteria: arterial pH <7.30 (regardless of encephalopathy grade) or the combination of prothrombin time >100 seconds and serum creatinine >300 μmol/L in patients with grade III or IV hepatic encephalopathy. 1
Clinical Assessment and Early Referral
Early recognition and prompt referral of acetaminophen toxicity cases to transplant centers is critical for improving outcomes. The comparative lack of precision in predicting outcomes early in acetaminophen-induced liver failure, combined with the potential for rapid progression, necessitates early referral to centers where both intensive medical therapy and transplantation are available 1.
King's College Criteria for Acetaminophen Toxicity
- Arterial pH <7.30 (regardless of encephalopathy grade)
- OR Prothrombin time >100 seconds AND serum creatinine >300 μmol/L in patients with grade III or IV hepatic encephalopathy
Timing of Referral
Timing is crucial in managing acetaminophen toxicity. The British Society of Gastroenterology recommends early referral to transplant programs to facilitate optimal timing and outcomes 1. Despite the fact that a significant proportion of patients may recover without intensive measures, early transfer is justified given the potential for rapid deterioration.
Poor Prognostic Indicators
- Development of hepatorenal failure
- Advanced malnutrition
- Progression to grade III or IV hepatic encephalopathy
- Severe coagulopathy
- Metabolic acidosis
Special Considerations
Psychiatric Assessment
Psychiatric stability is particularly relevant in acetaminophen overdose cases and is often difficult to assess fully at the time transplantation is being considered 1. Major psychiatric sequelae after transplantation may occur and often manifest as non-compliance with immunosuppression.
Contraindications to Transplantation
Absolute contraindications include:
- AIDS
- Extrahepatic malignancy
- Advanced cardiopulmonary disease
Relative contraindications include:
- Active alcohol/substance misuse
- Severe psychiatric disorder
- Significant sepsis outside the extrahepatic biliary tree 1
Outcomes After Transplantation
Liver transplantation can be life-saving in acetaminophen toxicity cases that progress to acute liver failure. Studies show that approximately 8% of patients with acetaminophen-induced acute liver failure undergo liver transplantation, with survival rates around 71% at 3 weeks 2. Without transplantation, patients meeting King's College criteria have a poor prognosis 3.
Alternative Bridging Therapies
In cases where transplantation may be delayed or contraindicated, temporary extracorporeal support such as single-pass albumin dialysis (SPAD) may serve as a bridge to native liver recovery 3. However, these should not delay referral for transplantation evaluation when indicated.
Common Pitfalls to Avoid
- Delayed referral: Waiting too long to refer can lead to development of cerebral edema, sepsis, and multiorgan failure, significantly worsening post-transplant outcomes 1.
- Inadequate N-acetylcysteine (NAC) treatment: Ensure proper NAC administration, as it must be used within 8-12 hours post-ingestion to be optimally effective 4.
- Overlooking unintentional overdoses: Nearly half (48%) of acetaminophen-related acute liver failure cases result from unintentional overdoses, often involving multiple acetaminophen-containing products 2.
- Inadequate monitoring: Patients may present with liver failure days after ingestion with undetectable serum acetaminophen concentrations 5.
Early referral to a transplant center is essential even if transplantation ultimately proves unnecessary, as these centers can provide specialized care that may prevent progression to irreversible liver failure.