An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure

Dean W. Roberts, William M. Lee, Jack A. Hinson, Shasha Bai, Christopher J. Swearingen, R. Todd Stravitz, Adrian Reuben, Lynda Letzig, Pippa M. Simpson, Jody Rule, Robert J. Fontana, Daniel R Ganger, K. Rajender Reddy, Iris Liou, Oren Fix, Laura P. James*

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background & Aims A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the 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 analytic assay) to detect acetaminophen protein adducts. Methods 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 alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal–Wallis test or rank-sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non–acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusions The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management.

Original languageEnglish (US)
Pages (from-to)555-562.e3
JournalClinical Gastroenterology and Hepatology
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Acetaminophen
Immunoassay
Liver
Wounds and Injuries
High Pressure Liquid Chromatography
Advisory Committees
Serum
Causality
Point-of-Care Systems
Proteins
Acute Liver Failure
Poisons
Nonparametric Statistics
Alanine Transaminase
Registries
Research Personnel
Weights and Measures
Sensitivity and Specificity

Keywords

  • AcetaSTAT
  • Hepatitis
  • Hepatotoxicity
  • Metabolism

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Roberts, Dean W. ; Lee, William M. ; Hinson, Jack A. ; Bai, Shasha ; Swearingen, Christopher J. ; Stravitz, R. Todd ; Reuben, Adrian ; Letzig, Lynda ; Simpson, Pippa M. ; Rule, Jody ; Fontana, Robert J. ; Ganger, Daniel R ; Reddy, K. Rajender ; Liou, Iris ; Fix, Oren ; James, Laura P. / An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure. In: Clinical Gastroenterology and Hepatology. 2017 ; Vol. 15, No. 4. pp. 555-562.e3.
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title = "An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure",
abstract = "Background & Aims A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the 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 analytic assay) to detect acetaminophen protein adducts. Methods 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 alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal–Wallis test or rank-sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100{\%} sensitivity, 86.2{\%} specificity, a positive predictive value of 89.2{\%}, and a negative predictive value of 100{\%}. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non–acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusions The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management.",
keywords = "AcetaSTAT, Hepatitis, Hepatotoxicity, Metabolism",
author = "Roberts, {Dean W.} and Lee, {William M.} and Hinson, {Jack A.} and Shasha Bai and Swearingen, {Christopher J.} and Stravitz, {R. Todd} and Adrian Reuben and Lynda Letzig and Simpson, {Pippa M.} and Jody Rule and Fontana, {Robert J.} and Ganger, {Daniel R} and Reddy, {K. Rajender} and Iris Liou and Oren Fix and James, {Laura P.}",
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Roberts, DW, Lee, WM, Hinson, JA, Bai, S, Swearingen, CJ, Stravitz, RT, Reuben, A, Letzig, L, Simpson, PM, Rule, J, Fontana, RJ, Ganger, DR, Reddy, KR, Liou, I, Fix, O & James, LP 2017, 'An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure', Clinical Gastroenterology and Hepatology, vol. 15, no. 4, pp. 555-562.e3. https://doi.org/10.1016/j.cgh.2016.09.007

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure. / Roberts, Dean W.; Lee, William M.; Hinson, Jack A.; Bai, Shasha; Swearingen, Christopher J.; Stravitz, R. Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M.; Rule, Jody; Fontana, Robert J.; Ganger, Daniel R; Reddy, K. Rajender; Liou, Iris; Fix, Oren; James, Laura P.

In: Clinical Gastroenterology and Hepatology, Vol. 15, No. 4, 01.04.2017, p. 555-562.e3.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure

AU - Roberts, Dean W.

AU - Lee, William M.

AU - Hinson, Jack A.

AU - Bai, Shasha

AU - Swearingen, Christopher J.

AU - Stravitz, R. Todd

AU - Reuben, Adrian

AU - Letzig, Lynda

AU - Simpson, Pippa M.

AU - Rule, Jody

AU - Fontana, Robert J.

AU - Ganger, Daniel R

AU - Reddy, K. Rajender

AU - Liou, Iris

AU - Fix, Oren

AU - James, Laura P.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background & Aims A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the 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 analytic assay) to detect acetaminophen protein adducts. Methods 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 alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal–Wallis test or rank-sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non–acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusions The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management.

AB - Background & Aims A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the 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 analytic assay) to detect acetaminophen protein adducts. Methods 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 alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal–Wallis test or rank-sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non–acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusions The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management.

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KW - Hepatitis

KW - Hepatotoxicity

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