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    King's College Criteria for Acetaminophen Toxicity

    Recommends who should be immediately referred for liver transplant.
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    The KCC are a well-accepted criteria that show the degree of multiorgan dysfunction from acetaminophen-induced liver failure. Used alone or with serum lactate and phosphate, the KCC can predict patients with poor prognosis.

    The King’s College Criteria (KCC) were developed to determine which patients with fulminant hepatic failure (FHF) should be referred for liver transplant.

    • Apply to all (acute or chronic) acetaminophen ingestions with signs of severe acute liver injury.
    • There are no worldwide standard criteria for transplantation, but the KCC are the most widely applied.
    • The KCC indicators predict a poor prognosis, and select patients most likely to benefit from immediate liver transplant referral.
    • The etiology of the acute liver failure is important in determining indicators of poor prognosis (acetaminophen vs. other causes).
    • Metabolic acidosis alone OR combined grade III or IV hepatic encephalopathy AND a PT time > 100s AND creatinine > 3.4 mg/dL predicted 77% of total deaths.

    Points to keep in mind:

    • KCC is criticized for predicting mortality often when patients are too sick for transplant.
    • The use of prolonged N-acetylcysteine therapy - not standard when the KCC was created - has significantly lowered the complication rate and need for transplant.
    • PT values are often not comparable across laboratories (due to use of different reagents).
    • Serum lactate (marker of liver injury), and phosphate (marker of liver regeneration), have been used as alternative early prognostic indicators or adjuncts to the KCC.
    • Specific but not sensitive: that is, while fulfillment of the criteria carries a poor prognosis, lack of fulfillment can still carry an unfavorable outlook.

    Acetaminophen poisoning is the most common cause of acute liver failure in the US, the UK and many other countries. The only treatment option that radically improves the outcome of acute liver failure is emergency liver transplantation. Therefore proper identification of which to refer/transfer is critically important.

    In addition, appropriate transplant candidates must be identified as early as possible to provide a realistic window for a graft to become available.

    Other predictors of poor prognosis without transplant
    About the Creator
    Dr. John O'Grady
    Content Contributors
    • Vince Nguyen, MD

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    Advice

    The presence of one of the following should prompt a referral/transfer to a liver transplantation center:

    • Acidosis (admission arterial pH < 7.30) OR
    • Hepatic encephalopathy (grade III or IV), AND coagulopathy (PT > 100 s), AND acute kidney injury (creatinine > 3.4 mg/dL), OR
    • Hyperlactatemia (4-hour lactate > 3.5 mmol/L, or 12-hour lactate > 3.0 mmol/L), OR
    • Hyperphosphatemia (48-96 hour phosphate > 3.7 mg/dL) in patients with acetaminophen-induced fulminant hepatic failure.

    Management

    • All patients with acetaminophen-induced hepatotoxicity should receive N-acetylcysteine (see NAC calculator).
    • Frequent monitoring should be performed for coagulation parameters, complete blood counts, metabolic panels, blood gases, and blood glucose.
    • Serum aminotransferases and bilirubin should be monitored daily.
    • Patients should be monitored and treated for hypoglycemia, hypokalemia, and hypophosphatemia.
    • Fresh frozen plasma (FFP) is indicated only in the setting of active hemorrhage or prior to invasive procedures in coagulopathic patients. Prophylactic administration of FFP is not recommended since it does not improve mortality and can interfere with assessments of liver function.

    Critical Actions

    Patients with acute liver failure should be managed in centers with expertise in caring for these patients. This includes patients who do not yet appear to be gravely ill, since it can be hazardous to transfer patients later in the disease course.

    Formula

    Series of Yes/No Questions.

    Facts & Figures

    CriteriaPPVSensitivitySpecificityPredictive Accuracy
    Arterial pH < 7.300.950.490.990.81
    HE + PT + Cr0.670.450.940.83
    Lactate*0.810.950.92
    Phosphate**10.8910.98

    PPV = Positive predictive value; HE = Hepatic encephalopathy stage III/IV; PT = prothrombin time > 100 s; Cr = creatinine > 3.4 mg/dL

    * Either lactate > 3.5 mmol/L after early resuscitation, or > 3.0 mmol/L after full resuscitation.

    ** Phosphate > 3.7 mg/dL between 48 – 96 hours.

    For more information on Hepatic Encephelopathy Stages, click here.

    Evidence Appraisal

    • The King’s College Criteria (KCC) was derived from a retrospective review of 588 patients with fulminant hepatic failure (FHF) over 13 years. The predictors are slightly different based on the etiology of the FHF (acetaminophen versus other causes).
    • The arterial pH, hepatic encephalopathy (HE), prothrombin time, and creatinine predictors were derived from 310 acetaminophen-induced FHF patients and retrospectively validated on a separate 121 acetaminophen-induced FHF patients.
    • Strengths include: well-validated, and reflect the degree of multiorgan dysfunction.
    • Specific but not sensitive: that is, while fulfillment of the criteria carries a poor prognosis, lack of fulfillment can still carry an unfavorable outlook.
    • Patients were transferred to King’s College Hospital at a relatively late stage (median time of 51 hours after acetaminophen ingestion) and were the most severely ill (the majority of patients were admitted with HE stages III or IV). This may have affected the predictive values of the test criteria.
    • In a systematic review of 14 eligible studies, the estimated overall sensitivity and specificity of the KCC for predicting mortality were 58% and 95%, respectively.
    • The search for earlier prognostic indicators with a higher sensitivity for poor prognosis led to investigations of α-fetoprotein, coagulation factor V, ketone body ratio, lactate and phosphate.
    • Lactate and phosphate concentrations were initially found to have improved predictive ability to the KCC. Subsequent studies have shown slightly inferior predictive ability compared to the KCC.
    • The addition of lactate or phosphate to the KCC may improve sensitivity and negative predictive value.

    Literature

    Dr. John O'Grady

    About the Creator

    John O’Grady, MD, is a professor of hepatology at King’s College Hospital and Chairman of UK Transplant Liver Advisory Group. His interests include outcomes after liver transplantation, optimal immunosuppression via clinical trials and the impact of recurrent disease on long-term outcome. Dr. O’Grady has published about clinical aspects of liver transplantation and acute liver failure.

    To view Dr. John O'Grady's publications, visit PubMed

    Content Contributors
    • Vince Nguyen, MD