Despite intensive efforts utilizing current animal and in vitro models, the mechanisms involved in the hepatotoxicity of APAP are still not fully understood. This is exemplified by the hepatotoxicity of acetaminophen (APAP) overdose, a major cause ALF due to its extensive worldwide use as an analgesic. Although significant progress has been made in understanding the molecular mechanisms underlying DILI, our incomplete knowledge of its pathogenesis and inability to predict DILI is largely due to both discordance between human and animal DILI in preclinical drug development and a lack of models that faithfully recapitulate complex pathophysiological features of human DILI. Given the wide use of both prescribed and over the counter drugs, DILI has become a major health issue with a pressing need to find novel and effective therapies. Drug induced liver injury (DILI) is a major cause of acute liver failure (ALF) and one of the leading indications for liver transplantation in Western societies.

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