False positive acetaminophen concentrations in patients with liver injury (original) (raw)
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False positive acetaminophen concentrations in icteric serum
Practical Laboratory Medicine, 2016
Introduction: Serum concentrations of acetaminophen are measured to predict the risk of hepatotoxicity in cases of acetaminophen overdose and to identify acetaminophen use in patients with acute liver injury without a known cause. The acetaminophen concentration determines if treatment with N-acetyl cysteine, the antidote for acetaminophen poisoning, is warranted. Description: A 49-year-old woman was admitted to our hospital with a hepatic encephalopathy and a total serum bilirubin concentration of 442 mmol/l. The acetaminophen concentration of 11.5 mg/l was measured with an enzymatic-colorimetric assay, thus treatment with N-acetyl cysteine was started. Interestingly, the acetaminophen concentration remained unchanged (11.5-12.3 mg/l) during a period of 4 consecutive days. In contrast, the acetaminophen concentration measured by HPLC, a chromatographic technique, remained undetectable Discussion: In the presented case, elevated bilirubin was the most likely candidate to interfere with acetaminophen assay causing false positive results. Bilirubin has intense absorbance in the ultraviolet and visible regions of the electromagnetic spectrum and for that reason it causes interference in an enzymatic-colorimetric assay. Conclusion: False positive acetaminophen laboratory test results may be found in icteric serum, when enzymatic-colorimetric assays are used for determination of an acetaminophen concentration. Questionable acetaminophen results in icteric serum should be confirmed by a non-enzymatic method, by means of ultrafiltration of the serum, or by dilution studies.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2016
A rapid, reliable point-of-care assay to detect acetaminophen protein adducts in serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC, a sensitive and specific quantitative analytical assay) to detect acetaminophen protein adducts. We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of a...
Falsely Elevated Acetaminophen Levels in the Setting of Hyperbilirubinemia
Journal of Advances in Internal Medicine, 2013
IntroductIon Patients presenting with elevated transaminases and jaundice are routinely tested for viral, autoimmune and drug etiologies. Acetaminophen (APAP) toxicity is a common and treatable cause of toxic hepatitis and elevated APAP levels in the setting of acute liver injury usually imply that acetaminophen is a primary contributor to the injury. Rare case reports, however, have described elevated levels in the absence of APAP ingestion in patients with hyperbilirubinemia and this appears to be related to the interference of bilirubin with commonly used assays for APAP. cAse PresentAtIon A 51-year-old male with a past history of heavy alcohol abuse (½ litre of Vodka/day x 20 years) and hypertension presented to the emergency department with jaundice, tremors and visual hallucinations for two and a half weeks. Past medical history was notable for hypertension, prior pancreatitis and unsuccessful alcohol rehabilitation. His only medication was occasional ibuprofen and he adamantly denied acetaminophen use, which family members confirmed. Vital signs showed BP 124/67 mmHg, P 94 BPM, T 95.6 F and RR 18/min. Exam was remarkable for cutaneous and scleral icterus, asterixis, spider angiomas and ascites. Lab values showed: WBC of 21.6K/ul, total bilirubin of 38.6 mg/dl (direct >30.0 mg/dl), AST of 209 U/L, ALT of 97 U/L, INR of 3.00, BUN of 55 mg/dl, Creatinine of 5.2 mg/dl and venous ammonia level of 255 ug/dl. Abdominal CT scan and ultrasound confirmed cirrhosis, fatty liver, ascites and portal hypertension (figures 1). A diagnostic paracentesis excluded SBP. Gastroenterology and nephrology consultations were obtained and recommended treatment for hepatorenal syndrome due to alcoholic hepatitis with Albumin, Octreotide and Midodrine.
Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2015
Acetaminophen-cysteine adducts (APAP-CYS) are a serum biomarker of acetaminophen exposure, formed when the oxidative metabolite of acetaminophen binds to cysteine residues of hepatic proteins. APAP-CYS adducts become elevated in cases of acute liver failure following acetaminophen overdose and have been proposed as a diagnostic tool to identify acetaminophen-induced acute liver failure when standard testing is inconclusive. A 26-year-old female with history of unexplained, severe hepatitis presented with a second episode of severe hepatitis including coagulopathy and transaminase levels >10,000 U/L. The patient reported ingesting "only a couple" of acetaminophen tablets several days prior to her presentation. An acetaminophen concentration of 14 mcg/mL at presentation aroused suspicion that acetaminophen might have caused the patient's liver failure, despite her adamant denial of overdose. APAP-CYS adduct levels measured from serum obtained 4 days after her presenta...
Does Therapeutic Use of Acetaminophen Cause Acute Liver Failure?
Pharmacotherapy, 2007
To compare the reported occurrence of liver failure in subjects in prospective trials with that in patients in retrospective reports after repeated use of therapeutic dosages of acetaminophen. Design. Systematic review of the medical literature. Data Source. MEDLINE and EMBASE biomedical and pharmacologic databases. Subjects. Adults who received repeated dosing of acetaminophen 4 g/day or lower for at least 24 hours. Measurements and Main Results. Articles written in several languages were abstracted by trained personnel using a structured abstraction form. Data were categorized by methodology (prospective vs retrospective), acetaminophen dosage, and type of liver effect. A total of 791 articles were identified, which included 30,865 subjects in prospective studies and 9337 patients in retrospective reports. The prospective studies reported no cases of fulminant hepatic injury, liver transplantation, or death due to acetaminophen. Of the 30,865 subjects in these studies, 129 (0.4%) were identified who had a serum aminotransferase level that exceeded the upper limit of normal, including 61 subjects in randomized trials in which the proportion of serum aminotransferase level increase was the same as or less than that in the placebo group and 68 subjects in trials without a placebo group. In addition, 4263 (13.8%) received the maximum recommended therapeutic dosage (3.9-4 g/day). In the retrospective reports, 96 patients (1.0%) had a serum alanine aminotransferase level that exceeded the upper limit of normal, one (0.01%) underwent liver transplantation, and six (0.06%) died. Causality relationship of acetaminophen for each retrospective case was assessed with the Naranjo adverse drug reaction probability scale. The mean ± SD Naranjo score for all 103 retrospective cases was 3.2 ± 1.9, indicating a possible relationship between the increased aminotransferase levels and acetaminophen use. Some retrospective reports contained information suggesting that the patient had ingested an overdose despite a history of therapeutic use. Conclusion. Prospective studies indicated that repeated use of a true therapeutic acetaminophen dosage may slightly increase the level of serum aminotransferase activity, but hepatic failure or death was not reported. Retrospective reports indicated a higher rate of increased serum aminotransferase levels, and several reported associated liver injury and death. The differing results and presence of evidence indicating inaccurate acetaminophen dosage information in some case reports suggests that these cases may be inadvertent overdoses, rather than true therapeutic dosages.
Acetaminophen dose does not predict outcome in acetaminophen-induced acute liver failure
Journal of Investigative …, 2010
Background: Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator.
Drug Metabolism and Disposition, 2002
Acetaminophen-induced hepatotoxicity has been attributed to covalent binding of the reactive metabolite N-acetyl-p-benzoquinone imine to cysteine groups on proteins as an acetaminophen-cysteine conjugate. We report a high-performance liquid chromatography with electrochemical detection (HPLC-ECD) assay for the conjugate with increased sensitivity compared with previous methods. Previous methods to quantitate the protein-bound conjugate have used a competitive immunoassay or radiolabeled acetaminophen. With HPLC-ECD, the protein samples are dialyzed and then digested with protease. The acetaminophen-cysteine conjugate is then quantified by HPLC-ECD using tyrosine as an internal reference. The lower limit of detection of the assay is approximately 3 pmol/mg of protein. Acetaminophen protein adducts were detected in liver and serum as early as 15 min after hepatotoxic dosing of acetaminophen to mice. Adducts were also detected in the serum of acetaminophen overdose patients. Analysis of human serum samples for the acetaminophen-cysteine conjugate revealed a positive correlation between acetaminophen-cysteine conjugate concentration and serum aspartate aminotransferase (AST) activity or time. Adducts were detected in the serum of patients even with relatively mild liver injury, as measured by AST and alanine aminotransferase. This assay may be useful in the diagnostic evaluation of patients with hepatotoxicity of an indeterminate etiology for which acetaminophen toxicity is suspect.
Analytical and Bioanalytical Chemistry, 2011
Acetaminophen antibodies were purified using affinity chromatography and labelled with horseradish peroxidase (HRP). The antibody-HRP conjugate and a new acetaminophen derivative were used in the construction of two immunoassay methods facilitating the direct quantitative measurement of acetaminophen in serum: a 96well microtitre plate and coated-tube ELISAs. A minimum detection limit of 0.2 μg mL −1 and a dynamic range of 0.2 to 10 μg mL −1 in serum were achieved using the 96-well microtitre plate ELISA. The tube assay was optimised for the measurement of the clinically critical acetaminophen concentration of 50 to 250 μg mL −1 of serum. The quantitative and specific tests could be completed within less than an hour. Common drugs including aspirin showed less than 0.1% cross-reactivity.