title: An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.
abstract: OBJECTIVE
  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.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas; Acetaminophen Toxicity Diagnostics, LLC, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas.
authors.forename: Dean W
authors.initials: DW
authors.lastname: Roberts
authors.affiliation: Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas; Acetaminophen Toxicity Diagnostics, LLC, Little Rock, Arkansas.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Hinson
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas.
authors.forename: Shasha
authors.initials: S
authors.lastname: Bai
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Swearingen
authors.affiliation: Virginia Commonwealth University, Richmond, Virginia.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Adrian
authors.initials: A
authors.lastname: Reuben
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas.
authors.forename: Lynda
authors.initials: L
authors.lastname: Letzig
authors.affiliation: Children's Hospital of Wisconsin Research Institute, Ann Arbor, Michigan.
authors.forename: Pippa M
authors.initials: PM
authors.lastname: Simpson
authors.affiliation: Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Jody
authors.initials: J
authors.lastname: Rule
authors.affiliation: University of Michigan, Ann Arbor, Michigan.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: Northwestern University, Chicago, Illinois.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ganger
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Iris
authors.initials: I
authors.lastname: Liou
authors.affiliation: University of California, San Francisco, California.
authors.forename: Oren
authors.initials: O
authors.lastname: Fix
authors.affiliation: 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.
authors.forename: Laura P
authors.initials: LP
authors.lastname: James
mesh_terms: D000082:Acetaminophen / Q000032:analysis*; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D055664:Electrochemical Techniques / Q000379:methods; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008099:Liver / Q000503:physiopathology*; D017114:Liver Failure, Acute / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D011506:Proteins / Q000737:chemistry*; D012680:Sensitivity and Specificity; D044967:Serum / Q000737:chemistry*; D055815:Young Adult
chemical_list: D011506:Proteins; D000082:Acetaminophen
keywords: AcetaSTAT; Hepatitis; Hepatotoxicity; Metabolism