Stratification of paracetamol overdose patients using new toxicity biomarkers: current candidates and future challenges.

One of the most common causes of acute liver failure in the Western world is paracetamol (acetaminophen) overdose. Specific and sensitive detection of liver injury is important for the prompt and safe treatment of patients with the antidote N-acetylcysteine (NAC) and for the determination of NAC efficacy. Despite many years of intense research, the precise mechanisms of paracetamol-induced liver injury in humans are still not defined, and few studies have examined the optimal dosing regimen for clinical NAC use. It has been widely acknowledged that circulating biomarkers such as microRNA-122, keratin-18 and high mobility group box-1 hold potential to inform on the mechanistic-basis of human drug-induced liver injury. Here, we provide a perspective on the application of these mechanistic biomarkers to the deeper understanding of paracetamol hepatotoxicity in clinical and preclinical studies. Also, we discuss current barriers to using these experimental biomarkers to stratify patients presenting to hospital with this common medical emergency.