Recent Advances in Acetaminophen Hepatotoxicity
Acetaminophen (paracetamol, APAP) is one of the most consumed analgesic and anti-pyretic drugs in the world. Generally considered safe at therapeutic doses, intentional or unintentional overdosing can cause severe liver injury and even acute liver failure. In Western countries, APAP is responsible for thousands of hospitalizations annually and is the major cause of acute liver failure. Since the establishment of the clinically relevant mouse model in 1973, numerous studies investigating the mechanism of APAP-induced liver injury have been published. Based on early mechanistic insight, the current standard of care, N-acetylcysteine (NAC), was developed. Although NAC is still the only clinically approved antidote available, additional mechanistic insight led to the discovery of promising new drugs, such as fomepizole, which, based on the solid understanding of its mechanism of action and proven safety profile, is under clinical development. Further drugs or compounds with various modes of action are also under consideration as future antidotes. In addition to the intracellular mechanisms of injury, the inflammatory response, which can aggravate the injury or promote regeneration and recovery, is another focus of research. However, no viable drug candidates promoting regeneration have been identified. This Special Issue is aimed at providing selected contributions on advances in the mechanistic understanding of APAP-induced liver injury and the regeneration and identification of new therapeutic targets and interventions.
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