Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure
Open Access
- 4 November 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 53 (2), 567-576
- https://doi.org/10.1002/hep.24060
Abstract
Despite extensive investigations, the cause of liver injury in 14% of patients with acute liver failure remains unknown (indeterminate). In a pilot study using a novel assay, highly specific acetaminophen‐cysteine adducts were detected in 7 of 36 indeterminate patients (19%). To extend these observations, sera from 110 subjects enrolled in the Acute Liver Failure Study Group registry with indeterminate acute liver failure were analyzed with a similar but more efficient and sensitive adduct assay. As positive controls, another 199 patients with known or presumed acetaminophen‐induced liver failure were assessed for the presence and quantity of adducts. Clinical, laboratory, and outcome data were compared for the two groups. On the basis of previous data for known therapeutic exposures and acetaminophen overdoses, an adduct concentration ≥1.0 nmol/mL of serum indicated a definite acetaminophen overdose. Among the 110 indeterminate cases, 18% had assay values ≥1.0 with a median level of 9.2 nmol/mL; 94.5% of the positive controls (known acetaminophen cases) had values ≥1.0 nmol/mL. Regardless of the initial diagnosis, subjects with elevated adduct levels demonstrated the clinical profile and hyperacute biochemical injury pattern associated with acetaminophen overdose: a predominance of female gender, very high aminotransferase levels, and low bilirubin levels. Conclusion: These data confirm and extend previous observations regarding the high (18%) prevalence of unrecognized or uncertain acetaminophen toxicity among subjects with indeterminate acute liver failure. N‐Acetylcysteine use was limited in this group, presumably because of the lack of a specific diagnosis of acetaminophen toxicity. (HEPATOLOGY 2011;53:567‐576.)This publication has 19 references indexed in Scilit:
- Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver FailureGastroenterology, 2009
- Pharmacokinetics of Acetaminophen-Protein Adducts in Adults with Acetaminophen Overdose and Acute Liver FailureDrug Metabolism and Disposition, 2009
- Acetaminophen-Associated Hepatic Injury: Evaluation of Acetaminophen Protein Adducts in Children and Adolescents With Acetaminophen OverdoseClinical Pharmacology & Therapeutics, 2008
- Detection and diagnosis of herpes simplex virus infection in adults with acute liver failureLiver Transplantation, 2008
- Intensive care of patients with acute liver failure: Recommendations of the U.S. Acute Liver Failure Study GroupCritical Care Medicine, 2007
- Brief Report: No Evidence for Parvovirus B19 or Hepatitis E Virus as a Cause of Acute Liver FailureDigestive Diseases and Sciences, 2006
- Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective studyHepatology, 2005
- Investigation of SEN Virus Infection in Patients with Cryptogenic Acute Liver Failure, Hepatitis‐Associated Aplastic Anemia, or Acute and Chronic Non–A–E HepatitisThe Journal of Infectious Diseases, 2003
- Hepatitis B infection in patients with acute liver failure in the United StatesHepatology, 2001
- A model to predict survival in patients with end-stage liver diseaseHepatology, 2001