Falsely Elevated Acetaminophen Levels In Patients With Hyperbilirubinemia

INTRODUCTION: Acetaminophen toxicity is the most common cause of Acute Liver Failure (ALF) in the U.S. In suspected overdose, the drug level is usually quantified using an enzymatic colorimetric assay. We report a case of falsely elevated acetaminophen levels due to interference from bilirubin or its byproducts when using an enzymatic colorimetric assay. CASE DESCRIPTION/METHODS: A 56-year-old woman with alcoholic hepatitis was admitted due to hepatic encephalopathy secondary to medication noncompliance. On exam, she was lethargic, disoriented, diffusely jaundiced with scleral icterus, and had asterixis. Admission labs showed total bilirubin 45.6 mg/dL, aspartate aminotransferase 55 units/L, alanine aminotransferase 38 units/L, total alkaline phosphatase 179 units/L, international normalized ratio 3.1, and acetaminophen 21.8 mg/L (reference level 9.1–17.4). She was treated for acetaminophen toxicity with N-Acetylcysteine (NAC) 20-hour IV protocol. Despite treatment, the acetaminophen level remained elevated the following morning (20.0 mg/L). She received three further doses of NAC; however, acetaminophen levels remained elevated at 19.5 mg/L (day 5). After literature review, it was thought that this could represent a false elevation of acetaminophen in the setting of elevated total bilirubin and no further treatment was given. The patient's encephalopathy resolved with lactulose and she was discharged home. The acetaminophen level was initially quantified as supratherapeutic using an enzymatic colorimetric assay. Due to persistent elevation of acetaminophen despite treatment with NAC, the serum sample was re-analyzed using liquid chromatography/tandem mass spectroscopy (LC/MS); acetaminophen was not detected with LC/MS. DISCUSSION: Falsely elevated acetaminophen levels may result when enzymatic colorimetric assays are used in the setting of hyperbilirubinemia due to interference of bilirubin and/or its metabolites. In cases where clinical suspicion for acetaminophen toxicity is low; acetaminophen levels remain elevated despite treatment with NAC; and patient has concomitant hyperbilirubinemia due to other etiologies (acute viral hepatitis, alcoholic hepatitis, etc.), it may be prudent to verify acetaminophen level with a non-photometric assay (LC/MS, immunoassays) before giving further NAC. Although NAC may have a role for treatment in non-acetaminophen causes of ALF, it may worsen outcomes in patients prone to volume overload and carries a risk of anaphylactic reactions.Figure 1.: Total Bilirubin and Acetaminophen Levels.