Article Abstract

Noncoding RNAs as therapeutics for acetaminophen-induced liver injury

Authors: Benjamin L. Woolbright, Hartmut Jaeschke


Acetaminophen- (APAP) induced acute liver failure (ALF) is a major cause of morbidity and mortality in the US (1). Currently, the major therapeutic is N-acetylcysteine (NAC), which is highly effective when given within 8 h of drug overdose. However, late-presenting patients commonly have poor outcomes, and NAC is not effective in these patients. As such, additional therapeutics are urgently needed to treat late-presenting patients. Critical to the generation of new drugs is the continued development of our understanding of APAP-induced ALF in human patients. While a number of recent papers from our group and others have made considerable advances in understanding mechanisms of toxicity in patients and human hepatocytes (2-5), there is still a lack of actionable therapeutic targets. Liver transplantation is the gold standard procedure for treating late-stage ALF but this operation is expensive and comes with additional costs of lifelong anti-rejection medication. In addition, due to limited donor organs, this therapeutic option is not always available (1). There are also ethical issues to consider as a majority of APAP-induced liver injury cases are due to attempted suicide. It is thus imperative that new modalities of treatment, including novel pharmacological agents, be explored for patients who suffer from drug-induced liver injury and acute liver failure.