Acetaminophen protein adducts: A review

Significant controversy surrounds the clinical and legal implications of 3-para cysteinyl acetaminophen, the protein degradation product of acetaminophen protein adducts. Versions of this test have been used for several years in animal research to help understand acetaminophen toxicity. As human research papers have appeared, the allegation has been made that the presence of 3-para cysteinyl acetaminophen in a patient with hepatic injury proves causal association of acetaminophen with the injury. It has also been suggested that quantitative adduct assays can guide the management of acute overdose or repeated supra-therapeutic use of acetaminophen by determining the need for initiating therapy and the timing of the end of therapy. The purpose of this review is to discuss the nature of this molecule and the detection assay, the animal research linking it with injury, and to evaluate the human research - specifically the evidence regarding causality and clinical utility. At the current time there is inadequate evidence for the test alone to prove causal association between acetaminophen and hepatic injury. Also, since quantitative 3-para cysteinyl acetaminophen assays parallel other markers of liver injury, it is not clear that assays alone will guide therapy unless quantitative assay markers can be shown to precede other markers (in elevation or decline) or provide more specificity than the Rumack-Matthew risk categorization nomogram. These advantages have not been demonstrated.