Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause

Laura P. James, Estella M. Alonso, Linda S. Hynan, Jack A. Hinson, Timothy J. Davern, William M. Lee, Robert H. Squires, Norberto Rodriguez-Baez, Karen F. Murray, Ross W. Shepherd, Phillip Rosenthal, Benjamin L. Schneider, Sukru Emre, Simon Horslen, Martin G. Martin, M. James Lopez, Brendan M. McGuire, Michael Narkewicz, Maureen Jonas, Kathleen SchwarzSteven Lobritto, Daniel W. Thomas, Liz Rand, Anil Dhawan, Vicky Ng, Deirdre A. Kelly, Ruben E. Quiros, Joel E. Lavine, Humberto Soriano

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

OBJECTIVE. Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS. Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses. RESULTS. Acetaminophen cysteine protein adduct was detected in 90% of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5% of samples from children with acute liver failure of indeterminate cause, and 9.6% of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission. CONCLUSIONS.A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.

Original languageEnglish (US)
Pages (from-to)e676-e681
JournalPediatrics
Volume118
Issue number3
DOIs
StatePublished - Sep 1 2006

Fingerprint

Acute Liver Failure
Acetaminophen
Proteins
Spontaneous Remission
Liver
Wounds and Injuries
Laboratory Animals
Aspartate Aminotransferases
acetaminophen cysteine
Serum
Alanine Transaminase
Bilirubin
Transplantation
High Pressure Liquid Chromatography

Keywords

  • Acetaminophen
  • Alanine aminotransferase
  • Liver failure

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

James, L. P., Alonso, E. M., Hynan, L. S., Hinson, J. A., Davern, T. J., Lee, W. M., ... Soriano, H. (2006). Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Pediatrics, 118(3), e676-e681. https://doi.org/10.1542/peds.2006-0069

Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. / James, Laura P.; Alonso, Estella M.; Hynan, Linda S.; Hinson, Jack A.; Davern, Timothy J.; Lee, William M.; Squires, Robert H.; Rodriguez-Baez, Norberto; Murray, Karen F.; Shepherd, Ross W.; Rosenthal, Phillip; Schneider, Benjamin L.; Emre, Sukru; Horslen, Simon; Martin, Martin G.; Lopez, M. James; McGuire, Brendan M.; Narkewicz, Michael; Jonas, Maureen; Schwarz, Kathleen; Lobritto, Steven; Thomas, Daniel W.; Rand, Liz; Dhawan, Anil; Ng, Vicky; Kelly, Deirdre A.; Quiros, Ruben E.; Lavine, Joel E.; Soriano, Humberto.

In: Pediatrics, Vol. 118, No. 3, 01.09.2006, p. e676-e681.

Research output: Contribution to journalArticle

James, LP, Alonso, EM, Hynan, LS, Hinson, JA, Davern, TJ, Lee, WM, Squires, RH, Rodriguez-Baez, N, Murray, KF, Shepherd, RW, Rosenthal, P, Schneider, BL, Emre, S, Horslen, S, Martin, MG, Lopez, MJ, McGuire, BM, Narkewicz, M, Jonas, M, Schwarz, K, Lobritto, S, Thomas, DW, Rand, L, Dhawan, A, Ng, V, Kelly, DA, Quiros, RE, Lavine, JE & Soriano, H 2006, 'Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause', Pediatrics, vol. 118, no. 3, pp. e676-e681. https://doi.org/10.1542/peds.2006-0069
James LP, Alonso EM, Hynan LS, Hinson JA, Davern TJ, Lee WM et al. Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Pediatrics. 2006 Sep 1;118(3):e676-e681. https://doi.org/10.1542/peds.2006-0069
James, Laura P. ; Alonso, Estella M. ; Hynan, Linda S. ; Hinson, Jack A. ; Davern, Timothy J. ; Lee, William M. ; Squires, Robert H. ; Rodriguez-Baez, Norberto ; Murray, Karen F. ; Shepherd, Ross W. ; Rosenthal, Phillip ; Schneider, Benjamin L. ; Emre, Sukru ; Horslen, Simon ; Martin, Martin G. ; Lopez, M. James ; McGuire, Brendan M. ; Narkewicz, Michael ; Jonas, Maureen ; Schwarz, Kathleen ; Lobritto, Steven ; Thomas, Daniel W. ; Rand, Liz ; Dhawan, Anil ; Ng, Vicky ; Kelly, Deirdre A. ; Quiros, Ruben E. ; Lavine, Joel E. ; Soriano, Humberto. / Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. In: Pediatrics. 2006 ; Vol. 118, No. 3. pp. e676-e681.
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abstract = "OBJECTIVE. Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS. Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses. RESULTS. Acetaminophen cysteine protein adduct was detected in 90{\%} of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5{\%} of samples from children with acute liver failure of indeterminate cause, and 9.6{\%} of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission. CONCLUSIONS.A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.",
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T1 - Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause

AU - James, Laura P.

AU - Alonso, Estella M.

AU - Hynan, Linda S.

AU - Hinson, Jack A.

AU - Davern, Timothy J.

AU - Lee, William M.

AU - Squires, Robert H.

AU - Rodriguez-Baez, Norberto

AU - Murray, Karen F.

AU - Shepherd, Ross W.

AU - Rosenthal, Phillip

AU - Schneider, Benjamin L.

AU - Emre, Sukru

AU - Horslen, Simon

AU - Martin, Martin G.

AU - Lopez, M. James

AU - McGuire, Brendan M.

AU - Narkewicz, Michael

AU - Jonas, Maureen

AU - Schwarz, Kathleen

AU - Lobritto, Steven

AU - Thomas, Daniel W.

AU - Rand, Liz

AU - Dhawan, Anil

AU - Ng, Vicky

AU - Kelly, Deirdre A.

AU - Quiros, Ruben E.

AU - Lavine, Joel E.

AU - Soriano, Humberto

PY - 2006/9/1

Y1 - 2006/9/1

N2 - OBJECTIVE. Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS. Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses. RESULTS. Acetaminophen cysteine protein adduct was detected in 90% of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5% of samples from children with acute liver failure of indeterminate cause, and 9.6% of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission. CONCLUSIONS.A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.

AB - OBJECTIVE. Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS. Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses. RESULTS. Acetaminophen cysteine protein adduct was detected in 90% of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5% of samples from children with acute liver failure of indeterminate cause, and 9.6% of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission. CONCLUSIONS.A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.

KW - Acetaminophen

KW - Alanine aminotransferase

KW - Liver failure

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