Acetaminophen hepatotoxicity: an updated review

Highlight report: acetaminophen hepatotoxicity

“…However, because the majority of patients with an overdose do not show such serve consequences, the new UK standard means that one life is saved every 2 years associated with costs of 17.3 million euros per saved life. This underlines the urgent need of better predictive biomarkers (Lancaster et al 2015).…”

“…Lancaster and colleagues discuss a case in which a patient died, who did not receive N-acetylcysteine according to the '200 µg/ml line'. Therefore, it became standard in the UK to treat any patient with serum APAP equivalent to only 100 µg/ml at 4 h after intoxication (Lancaster et al 2015). However, because the majority of patients with an overdose do not show such serve consequences, the new UK standard means that one life is saved every 2 years associated with costs of 17.3 million euros per saved life.…”

“…The article of Lancaster et al (2015) is also of relevance for the field of alternative methods (Hammad 2013;Ghallab 2013Ghallab , 2014aReif 2014a, b;Godoy 2011). Currently, intensive research activities are ongoing to establish in vitro systems particularly for hepatotoxicity (Grinberg et al 2014;Ramaiahgari et al 2014;Rodrigues et al 2013;Schug et al 2013), nephrotoxicity (Sanchez-Niño et al 2014;Fujiki et al 2013;, neurotoxicity (Barbosa et al 2014;Sisnaiske et al 2014;Frimat et al 2010) and developmental toxicity (Krug et al 2013;Rempel et al 2015;Balmer et al 2014;Zimmer et al 2014).…”

“…However, it can often be observed that in vitro studies used very high APAP concentrations in the range of 10 mM or even higher. The review of Lancaster et al (2015) reminds us of the time-honored '200 µg/ml line', which means that a serum concentration of 200 µg APAP/ml 4 h after oral uptake represents a threshold above which the risk of acute liver failure significantly increases. Considering the molecular weight of APAP of 151.16 g/ mol this corresponds to a threshold of 1.3 mM.…”

“…Acetaminophen (APAP) represents the leading cause of liver failure in Europe (Lancaster et al 2015). Much effort has been invested to gain a better understanding of the molecular mechanisms of APAP hepatotoxicity (Saito et al 2010;Kon et al 2004;Hwang et al 2015;Sjogren et al 2014;Schyschka et al 2013;Singh et al 2013) and to identify biomarkers of APAP overdose (McGill et al 2014;Beger et al 2015).…”