What are the King's College criteria for liver transplantation in patients with acute liver failure?

King's College Criteria for Liver Transplantation in Acute Liver Failure

The King's College Criteria are the most widely validated and utilized prognostic criteria for determining liver transplantation need in patients with acute liver failure, with separate criteria for acetaminophen and non-acetaminophen etiologies. 1

Acetaminophen-Induced Acute Liver Failure Criteria:

Either of the following:

• Arterial pH <7.3 (following adequate volume resuscitation) irrespective of encephalopathy grade 1
• OR all three of the following:
  • PT >100 seconds (INR >6.5) 1
  • Serum creatinine >300 μmol/L (3.4 mg/dL) 1
  • Grade III or IV hepatic encephalopathy 1

Non-Acetaminophen-Induced Acute Liver Failure Criteria:

Either of the following:

• PT >100 seconds (INR >6.5) irrespective of encephalopathy grade 1
• OR any three of the following (irrespective of encephalopathy grade):
  • Etiology: non-A, non-B hepatitis (indeterminate), drug-induced liver injury 1
  • Age <10 or >40 years 1
  • Jaundice to encephalopathy interval >7 days 1
  • PT >50 seconds (INR >3.5) 1
  • Serum bilirubin >300 μmol/L 1

Prognostic Value and Limitations

Strengths:

• High specificity (94.6%) and positive predictive value for poor outcomes 1, 2
• Most extensively validated criteria for acute liver failure prognosis 1
• Well-established clinical utility in transplant decision-making 1

Limitations:

• Limited sensitivity (58.2%) - may miss patients who could benefit from transplantation 1, 2
• Negative predictive value varies widely (25-94%), meaning failure to meet criteria doesn't guarantee survival 1
• Recent analyses suggest these criteria may not be as predictive in all populations 1

Alternative and Supplementary Prognostic Markers

• Arterial lactate levels: Levels >3.5 mmol/L after 4 hours or >3.0 mmol/L after 12 hours of management with volume resuscitation indicate poor prognosis 1
• Factor V levels: Levels <20% in patients with encephalopathy have been used in some centers (Clichy-Villejuif criteria) 1
• MELD score: A MELD score >30 has higher sensitivity but lower specificity than King's College Criteria 3, 4
• Hepatic encephalopathy grade: Grade III-IV encephalopathy is associated with worse outcomes (33% transplant-free survival vs. 52% for grade I-II) 1
• Arterial ammonia levels: Sustained levels between 150-200 mmol/L correlate with higher risk of cerebral edema and poor outcomes 1

Clinical Application

• Early referral to a liver transplantation center is recommended for all patients with acute liver failure 1
• Patients with non-acetaminophen acute liver failure should be referred to a transplant center regardless of encephalopathy status 1
• Patients with progressive coagulopathy even without encephalopathy should be discussed with a transplant center 1
• Certain etiologies (Wilson disease, mushroom poisoning) carry particularly poor prognosis and may warrant more urgent consideration for transplantation 1

Common Pitfalls to Avoid

• Relying solely on King's College Criteria without considering other prognostic factors may miss patients who could benefit from transplantation 1
• Delayed referral to transplant centers worsens outcomes - early consultation is critical 1
• Failure to recognize that etiology significantly impacts prognosis (acetaminophen, hepatitis A, pregnancy-related ALF have better outcomes than other causes) 1
• Over-reliance on any single prognostic system - combining multiple criteria may improve accuracy 1, 3