Dean W Roberts1, William M Lee2, Jack A Hinson3, Shasha Bai4, Christopher J Swearingen4, R Todd Stravitz5, Adrian Reuben6, Lynda Letzig4, Pippa M Simpson7, Jody Rule2, Robert J Fontana8, Daniel Ganger9, K Rajender Reddy10, Iris Liou11, Oren Fix12, Laura P James13. 1. University of Arkansas for Medical Sciences, Little Rock, Arkansas; Acetaminophen Toxicity Diagnostics, LLC, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas. 2. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas. 3. University of Arkansas for Medical Sciences, Little Rock, Arkansas; Acetaminophen Toxicity Diagnostics, LLC, Little Rock, Arkansas. 4. University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas. 5. Virginia Commonwealth University, Richmond, Virginia. 6. Medical University of South Carolina, Charleston, South Carolina. 7. Children's Hospital of Wisconsin Research Institute, Ann Arbor, Michigan. 8. University of Michigan, Ann Arbor, Michigan. 9. Northwestern University, Chicago, Illinois. 10. University of Pennsylvania, Philadelphia, Pennsylvania. 11. University of Washington, Seattle, Washington. 12. University of California, San Francisco, California. 13. University of Arkansas for Medical Sciences, Little Rock, Arkansas; Acetaminophen Toxicity Diagnostics, LLC, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas. Electronic address: jameslaurap@uams.edu.
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.
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.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Kenneth L Muldrew; Laura P James; Leslie Coop; Sandra S McCullough; Howard P Hendrickson; Jack A Hinson; Philip R Mayeux Journal: Drug Metab Dispos Date: 2002-04 Impact factor: 3.922
Authors: Yuchao Xie; Mitchell R McGill; Sarah F Cook; Matthew R Sharpe; Robert D Winefield; Diana G Wilkins; Douglas E Rollins; Hartmut Jaeschke Journal: Xenobiotica Date: 2015-04-14 Impact factor: 1.908
Authors: Anne M Larson; Julie Polson; Robert J Fontana; Timothy J Davern; Ezmina Lalani; Linda S Hynan; Joan S Reisch; Frank V Schiødt; George Ostapowicz; A Obaid Shakil; William M Lee Journal: Hepatology Date: 2005-12 Impact factor: 17.425
Authors: L P James; E V Capparelli; P M Simpson; L Letzig; D Roberts; J A Hinson; G L Kearns; J L Blumer; J E Sullivan Journal: Clin Pharmacol Ther Date: 2008-10-15 Impact factor: 6.875
Authors: Luqi Duan; Anup Ramachandran; Jephte Y Akakpo; James L Weemhoff; Steven C Curry; Hartmut Jaeschke Journal: Toxicol Lett Date: 2018-11-15 Impact factor: 4.372
Authors: Lisa C Casey; Robert J Fontana; Ariel Aday; David B Nelson; Jody A Rule; Michelle Gottfried; Minh Tran; William M Lee Journal: Hepatology Date: 2020-10-05 Impact factor: 17.425
Authors: Steven C Curry; Angela Padilla-Jones; Anne-Michelle Ruha; Ayrn D O'Connor; A Min Kang; Diana G Wilkins; Hartmut Jaeschke; Kelly Wilhelms; Richard D Gerkin Journal: J Med Toxicol Date: 2019-04-12