Measurement of serum acetaminophen-protein adducts in patients with acute liver failure

Timothy J. Davern, Laura P. James, Jack A. Hinson, Julie Polson, Anne M. Larson, Robert J. Fontana, Ezmina Lalani, Santiago Munoz, A. Obaid Shakil, William M. Lee

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

Background & Aims: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings. Acetaminophen-protein adducts are specific biomarkers of drug-related toxicity in animal models and can be measured in tissue or blood samples. Measurement of serum adducts might improve diagnostic accuracy in acute liver failure (ALF) patients. Methods: We measured serum acetaminophen-protein adducts using high-pressure liquid chromatography with electrochemical detection in coded sera of 66 patients with ALF collected prospectively at 24 US tertiary referral centers. Samples were included from 20 patients with well-characterized acetaminophen-related acute liver failure, 10 patients with ALF owing to other well-defined causes, 36 patients with ALF of indeterminate etiology, and 15 additional patients without ALF but with known acetaminophen overdose and minimal or no biochemical liver injury. Results: Acetaminophen-protein adducts were detected in serum in 100% of known acetaminophen ALF patients and in none of the ALF patients with other defined causes, yielding a sensitivity and specificity of 100%. In daily serial samples, serum adducts decreased in parallel with aminotransferase levels. Seven of 36 (19%) indeterminate cases demonstrated adducts in serum suggesting that acetaminophen toxicity caused or contributed to ALF in these patients. Low adduct levels were present in 2 of 15 patients with acetaminophen overdose without significant liver injury. Conclusions: Measurement of serum acetaminophen-protein adducts reliably identified acetaminophen toxicity, and may be a useful diagnostic test for cases lacking historical data or other clinical information.

Original languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalGastroenterology
Volume130
Issue number3
DOIs
StatePublished - Mar 2006

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Acute Liver Failure
Acetaminophen
Blood Proteins
Serum
Liver
Wounds and Injuries
Transaminases
Drug-Related Side Effects and Adverse Reactions
Routine Diagnostic Tests
Tertiary Care Centers
Proteins
Animal Models
Biomarkers
High Pressure Liquid Chromatography
Sensitivity and Specificity

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Davern, T. J., James, L. P., Hinson, J. A., Polson, J., Larson, A. M., Fontana, R. J., ... Lee, W. M. (2006). Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology, 130(3), 687-694. https://doi.org/10.1053/j.gastro.2006.01.033

Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. / Davern, Timothy J.; James, Laura P.; Hinson, Jack A.; Polson, Julie; Larson, Anne M.; Fontana, Robert J.; Lalani, Ezmina; Munoz, Santiago; Shakil, A. Obaid; Lee, William M.

In: Gastroenterology, Vol. 130, No. 3, 03.2006, p. 687-694.

Research output: Contribution to journalArticle

Davern, TJ, James, LP, Hinson, JA, Polson, J, Larson, AM, Fontana, RJ, Lalani, E, Munoz, S, Shakil, AO & Lee, WM 2006, 'Measurement of serum acetaminophen-protein adducts in patients with acute liver failure', Gastroenterology, vol. 130, no. 3, pp. 687-694. https://doi.org/10.1053/j.gastro.2006.01.033
Davern TJ, James LP, Hinson JA, Polson J, Larson AM, Fontana RJ et al. Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology. 2006 Mar;130(3):687-694. https://doi.org/10.1053/j.gastro.2006.01.033
Davern, Timothy J. ; James, Laura P. ; Hinson, Jack A. ; Polson, Julie ; Larson, Anne M. ; Fontana, Robert J. ; Lalani, Ezmina ; Munoz, Santiago ; Shakil, A. Obaid ; Lee, William M. / Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. In: Gastroenterology. 2006 ; Vol. 130, No. 3. pp. 687-694.
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AU - James, Laura P.

AU - Hinson, Jack A.

AU - Polson, Julie

AU - Larson, Anne M.

AU - Fontana, Robert J.

AU - Lalani, Ezmina

AU - Munoz, Santiago

AU - Shakil, A. Obaid

AU - Lee, William M.

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N2 - Background & Aims: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings. Acetaminophen-protein adducts are specific biomarkers of drug-related toxicity in animal models and can be measured in tissue or blood samples. Measurement of serum adducts might improve diagnostic accuracy in acute liver failure (ALF) patients. Methods: We measured serum acetaminophen-protein adducts using high-pressure liquid chromatography with electrochemical detection in coded sera of 66 patients with ALF collected prospectively at 24 US tertiary referral centers. Samples were included from 20 patients with well-characterized acetaminophen-related acute liver failure, 10 patients with ALF owing to other well-defined causes, 36 patients with ALF of indeterminate etiology, and 15 additional patients without ALF but with known acetaminophen overdose and minimal or no biochemical liver injury. Results: Acetaminophen-protein adducts were detected in serum in 100% of known acetaminophen ALF patients and in none of the ALF patients with other defined causes, yielding a sensitivity and specificity of 100%. In daily serial samples, serum adducts decreased in parallel with aminotransferase levels. Seven of 36 (19%) indeterminate cases demonstrated adducts in serum suggesting that acetaminophen toxicity caused or contributed to ALF in these patients. Low adduct levels were present in 2 of 15 patients with acetaminophen overdose without significant liver injury. Conclusions: Measurement of serum acetaminophen-protein adducts reliably identified acetaminophen toxicity, and may be a useful diagnostic test for cases lacking historical data or other clinical information.

AB - Background & Aims: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings. Acetaminophen-protein adducts are specific biomarkers of drug-related toxicity in animal models and can be measured in tissue or blood samples. Measurement of serum adducts might improve diagnostic accuracy in acute liver failure (ALF) patients. Methods: We measured serum acetaminophen-protein adducts using high-pressure liquid chromatography with electrochemical detection in coded sera of 66 patients with ALF collected prospectively at 24 US tertiary referral centers. Samples were included from 20 patients with well-characterized acetaminophen-related acute liver failure, 10 patients with ALF owing to other well-defined causes, 36 patients with ALF of indeterminate etiology, and 15 additional patients without ALF but with known acetaminophen overdose and minimal or no biochemical liver injury. Results: Acetaminophen-protein adducts were detected in serum in 100% of known acetaminophen ALF patients and in none of the ALF patients with other defined causes, yielding a sensitivity and specificity of 100%. In daily serial samples, serum adducts decreased in parallel with aminotransferase levels. Seven of 36 (19%) indeterminate cases demonstrated adducts in serum suggesting that acetaminophen toxicity caused or contributed to ALF in these patients. Low adduct levels were present in 2 of 15 patients with acetaminophen overdose without significant liver injury. Conclusions: Measurement of serum acetaminophen-protein adducts reliably identified acetaminophen toxicity, and may be a useful diagnostic test for cases lacking historical data or other clinical information.

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