Acetaminophen (APAP) is the most commonly used drug for the treatment of pain and fever in the world today. In large doses, APAP causes acute liver failure and is the leading cause of acute liver failure in the US. The current laboratory test for the diagnosis of APAP toxicity, measurement of APAP levels in peripheral blood, is only effective in the first 24 hours of APAP overdose. Acetaminophen Toxicity Diagnostics (ATD), LLC has developed a rapid, point-of-care diagnostic assay (dipstick) for the measurement of APAP protein adducts. Adducts are sensitive and specific biomarkers of APAP hepatotoxicity that may be detected in peripheral blood 6 to 7 days after a toxic overdose of APAP. The dipstick detects APAP irreversibly bound to proteins (APAP protein adducts) by using antibodies specific for adducts in the detection system. The dipstick is reliable, accurate and provides rapid results.
In Specific Aim 1, the dipstick will be calibrated to detect levels of APAP protein adducts corresponding to severe liver toxicity and 2000 precision manufactured, research use dipsticks will be produced.
In Specific Aim 2, the dipsticks will be tested internally for stability, specificity, and diagnostic sensitivity using stored, frozen clinical samples.
In Specific Aim 3, six major hepatology centers will participate in a study to measure dipstick performance in patients with acute liver injury and acute liver failure. Successful completion of these aims will establish the clinical utility of the dipstick, an innovation that will enhance the diagnosis of APAP toxicity.

Public Health Relevance

Acetaminophen is the most widely used drug for the treatment of pain and fever around the world. Large doses of acetaminophen can cause acute liver failure and death. Diagnostic tests are needed for patients that have acetaminophen related liver injury. The current laboratory test only works in the first 24 hours after acetaminophen overdose. Acetaminophen Toxicity Diagnostics, LLC has developed a rapid dipstick test that measures biomarkers of acetaminophen liver injury. These biomarkers (known as acetaminophen protein adducts) can be measured in the blood samples of patients with acetaminophen related liver injury for 6 to 7 days after the overdose. This project will further develop the dipstick test so that it can be available to physicians in the future.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
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Special Emphasis Panel (ZRG1-DKUS-E (10))
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Densmore, Christine L
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Acetaminophen Toxicity Diagnostics, LLC
Little Rock
United States
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Roberts, Dean W; Lee, William M; Hinson, Jack A et al. (2017) An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure. Clin Gastroenterol Hepatol 15:555-562.e3
Dobson, Nicole R; Liu, Xiaoxi; Rhein, Lawrence M et al. (2016) Salivary caffeine concentrations are comparable to plasma concentrations in preterm infants receiving extended caffeine therapy. Br J Clin Pharmacol 82:754-61
James, Laura; Yan, Ke; Pence, Lisa et al. (2015) Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity. PLoS One 10:e0131010
James, Laura; Roberts, Dean (2014) Isoniazid hepatotoxicity: progress in understanding the immunologic component. Hepatology 59:746-8
James, Laura P; Chiew, Angela; Abdel-Rahman, Susan M et al. (2013) Acetaminophen protein adduct formation following low-dose acetaminophen exposure: comparison of immediate-release vs extended-release formulations. Eur J Clin Pharmacol 69:851-7
James, Laura P; Gill, Prit; Simpson, Pippa (2013) Predicting risk in patients with acetaminophen overdose. Expert Rev Gastroenterol Hepatol 7:509-12
James, L; Ito, S (2009) Neonatal pharmacology: rational therapeutics for the most vulnerable. Clin Pharmacol Ther 86:573-7