Measurement of Serum Acetaminophen–Protein Adducts in Patients With Acute Liver Failure

Confirming the Causative Role of Acetaminophen in Indeterminate Acute Liver Failure Using Acetaminophen-Cysteine Adducts

“…Compared with a typical acetaminophen half-life in patients with ALF ranging from 5.4 to 18.4 h, the mean elimination half-life of APAP-CYS adducts is 41.3±8.3 h [2,8]. In one study, APAP-CYS adducts were detectable in serum for up to 12 days after acetaminophen ingestion [10]; in another, adducts were detected for up to 7 days after enrollment into the study [8]. This delayed clearance is critical in considering the utility of APAP-CYS adducts as a diagnostic test.…”

“…Patients with acetaminophen-related ALF often present for medical care at a later time and in later stages of hepatotoxicity than patients with ALF from other causes [2,8]. Late entry to care (>15 h) after acetaminophen overdose in patients without ALF on presentation is also associated with an increased risk of later developing liver failure [9].…”

“…For example, very high serum bilirubin concentrations can cause false positives for acetaminophen with certain assay methods [8]. Together, these limitations suggest that there may be many patients with indeterminate-cause ALF in whom a true association with acetaminophen is not identified by standard diagnostic methods.…”

“…Several studies have examined APAP-CYS concentrations in instances of indeterminate ALF and suggested that up to 18-19 % of adult cases may be associated with acetaminophen toxicity on the basis of adduct concentrations [6,8]. Moreover, adult patients with indeterminate ALF and elevated APAP-CYS concentrations shared the clinical and biochemical profile of patients with acetaminophen-associated ALF: hyperacute liver injury, high aminotransferase concentrations, low total bilirubin, a lower rate of transplantation, and a higher rate of spontaneous survival [6].…”

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

“…Some biomarkers such APAP-protein adducts can assist in diagnosing the likely cause of the liver injury and the severity of the overdose even several days after the poisoning [242]. This led to the recent development of a point-of-care test for the accelerated diagnosis of APAP overdose in patients [243].…”