Unrecognized Acetaminophen Toxicity as a Cause of Indeterminate Acute Liver Failure

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887, USA.
Hepatology (Impact Factor: 11.06). 02/2011; 53(2):567-76. DOI: 10.1002/hep.24060
Source: PubMed


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.

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Available from: Laura P James, Dec 16, 2013
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    • "Le principal est que l'utilisation pré coce du NAC dans les hé patites graves non lié es au paracé tamol, chez des patients pré sentant une encé phalopathie de Grade I ou II, a montré une amé lioration de la survie sans transplantation [8]. De plus, une e ´ tude ré cente a montré que parmi les patients pré sentant une hé patite fulminante d'e ´ tiologie inconnue, environ 18 % e ´ taient en fait secondaire a ` une toxicité du paracé tamol [9]. Devant l'innocuité relative du produit, son utilisation devant toute hé patite aiguë d'origine toxique ou non doit e ˆtre large aux mêmes doses que celles utilisé es dans le cadre de l'hé patite aiguë au paracé tamol. "
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    ABSTRACT: Many substances, drugs or not, can be responsible for acute hepatitis. Nevertheless, toxic etiology, except when that is obvious like in acetaminophen overdose, is a diagnosis of elimination. Major causes, in particular viral etiologies, must be ruled out. Acetaminophen, antibiotics, antiepileptics and antituberculous drugs are the first causes of drug-induced liver injury. Severity assessment of the acute hepatitis is critical. Acute liver failure (ALF) is defined by the factor V, respectively more than 50% for the mild ALF and less than 50% for the severe ALF. Neurological examination must be extensive to the search for encephalopathy signs. According to the French classification, fulminant hepatitis is defined by the presence of an encephalopathy in the two first weeks and subfulminant between the second and 12th week after the advent of the jaundice. During acetaminophen overdose, with or without hepatitis or ALF, intravenous N-acetylcysteine must be administered as soon as possible. In the non-acetaminophen related ALF, N-acetylcysteine improves transplantation-free survival. Referral and assessment in a liver transplantation unit should be discussed as soon as possible.
    Full-text · Article · Jun 2013 · Annales francaises d'anesthesie et de reanimation
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    • "Personal Communication, April 13th 2012). Paracetamol toxicity can be difficult to diagnose, however; one study suggests that 18% of indeterminate cases of liver failure referred to an American tertiary care centre were due to unrecognized paracetamol toxicity [20]. "
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    Full-text · Article · Jun 2012 · BMC Clinical Pharmacology
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    • "Clinical history, including the magnitude of the exposure, the timing of acetylcysteine administration, and laboratory markers of liver injury should also be taken into account when interpreting adduct concentrations in the lower range. A recent publication has described the use of APAP-CYS to identify occult acetaminophen poisoning among patenits with liver failure of unclear etiology[15]. It is likely that APAP-CYS will be a useful diagnostic test in cases in which the history and standard laboratory testing are not sufficient to establish acetaminophen as a cause of liver injury "
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    Full-text · Article · Mar 2011 · BMC Gastroenterology
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