False positive acetaminophen concentrations in patients with liver injury

Polson, Julie; Wians, Frank H.; Orsulak, Paul J.; Fuller, Dwain C.; Murray, Natalie; Koff, Jonathan M.; Khan, Adil I.; Balko, Jody; Hynan, Linda S.; Lee, William M.

doi:10.1016/j.cca.2008.01.018

Cited by 51 publications

(23 citation statements)

References 8 publications

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“…[42]). However, other studies seeking to detect evidence for additive effects of APAP use on liver injury during acute viral hepatitis or other causes of liver injury have instead found that some bioanalytical methods for the detection of APAP yield high rates of false positives in the presence of high bilirubin levels and thus may have resulted in overestimation of APAP use during acute liver disease in some studies [43]. …”

Section: Discussionmentioning

confidence: 99%

Susceptibility to acetaminophen (APAP) toxicity unexpectedly is decreased during acute viral hepatitis in mice

Getachew

James

Lee

et al. 2010

Biochemical Pharmacology

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Acetaminophen (APAP) hepatotoxicity results from cytochrome P450 metabolism of APAP to the toxic metabolite, n-acetyl-benzoquinone imine (NAPQI), which reacts with cysteinyl residues to form APAP adducts and initiates cell injury. As APAP is commonly used during viral illnesses there has been concern that APAP injury may be additive to that of viral hepatitis, leading physicians to advise against its use in such patients; this has not been investigated experimentally. We infected C57BL/6 male mice with replication-deficient adenovirus to produce moderately severe acute viral hepatitis and observed that APAP doses that were hepatotoxic or lethal in control mice produced neither death nor additional increase in serum ALT when administered to infected mice at the peak of virus-induced liver injury. Moreover, the concentration of hepatic APAP-protein adducts formed in these mice was only 10% that in control mice. Protection from APAP hepatotoxicity also was observed earlier in the course of infection, prior to the peak virus-induced ALT rise. Hepatic glutathione limits APAP-protein adduct formation but glutathione levels were similar in control and infected mice. Cyp1a2 (E.C. 1.14.14.1) and Cyp2e1 (E.C. 1.14.13.n7) mRNA expression decreased by 3 days post-infection and hepatic Cyp2e1 protein levels were reduced almost 90% at 7 days, when adduct formation was maximally inhibited. In vitro, hepatocytes from virally infected mice also were resistant to APAP-induced injury but sensitive to NAPQI. Rather than potentiating APAP-induced liver injury, acute viral hepatitis in this model resulted in selective down-regulation of APAP metabolizing P450s in liver and decreased the risk of APAP hepatotoxicity.

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Section: Discussionmentioning

confidence: 99%

Susceptibility to acetaminophen (APAP) toxicity unexpectedly is decreased during acute viral hepatitis in mice

Getachew

James

Lee

et al. 2010

Biochemical Pharmacology

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“…Polson et al concluded that false positive acetaminophen tests might result when enzymatic-colorimetric assays are used, typically when bilirubin exceeds 10 mg/dl. 4 Similarly, Bertholf et al selected 12 patients without a history of acetaminophen ingestion with serum bilirubin concentrations ranging from 15-34 mg/dl. They concluded that their data was consistent with bilirubin interference in the enzymatic and / or chromogenic reactions involved in the acetaminophen method, with no detectable acetaminophen levels when total bilirubin was <5 mg/dl.…”

Section: Discussionmentioning

confidence: 99%

Falsely Elevated Acetaminophen Levels in the Setting of Hyperbilirubinemia

Parekh

Manser

2013

J Adv Intern Med

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A 51-year-old male with a history of heavy alcohol abuse presented with alcoholic hepatitis and acute renal failure. Although he denied acetaminophen (APAP) ingestion, he was found to have elevated APAP levels that persisted and actually increased despite treatment with N-acetylcysteine. Review of the literature reveals that falsely elevated APAP levels may rarely occur with patients suffering from liver failure and felt to be related to severe hyperbilirubinemia. Interpretation of APAP levels in patients with severe liver disease and hyperbilirubinemia may be difficult and lead to diagnostic and therapeutic confusion. DOI: http://dx.doi.org/10.3126/jaim.v2i2.8782 Journal of Advances in Internal Medicine 2013;02(02):74-77

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“…For instance, Hullin et al reported high immunoglobulin levels affecting APAP quantification leading to underestimated amounts [11]. The presence of high endogenous bilirubin concentrations was also demonstrated to lead to false positive results [8,12]. Crossreactivity that is difficult to predict is also known to potentially affect immunoassays results [13].…”

Section: Introductionmentioning

confidence: 98%

“…The quantification methods used routinely in clinical chemistry or emergency toxicology are often based on immunoassays detection [8] or GC-MS(/MS) techniques [9,10]. Immunoassays are largely used but suffer from a lack of selectivity.…”

Section: Introductionmentioning

confidence: 99%