Roadmap for drug-induced liver injury
The liver is one of the organs most susceptible to drug toxicity, and in the clinic, drug-induced liver injury (DILI) has accounted for more than 50% of acute liver failure cases. Excluding acetaminophen, DILI accounts for approximately 14% of acute liver failures with a mortality rate of up to 10%. DILI is also a major cause of drug attrition, leading to withdrawal of potentially valuable therapies during preclinical testing, clinical trials and post-marketing.
It is clear that current preclinical testing paradigms based on a combination of various in vitro and in vivo models are poorly predictive, at a quantitative and mechanistic level, of the potential for a new drug candidate to cause DILI in humans, in particular those drugs that show poorly defined dose–response relationships and/or human-specific mechanisms of toxicity.
This new Perspective presents our vision for a DILI roadmap, with the aim of managing DILI risk and, ultimately, assisting in the design and development of safer and more effective medicines. Our approach comprises a tiered system, which integrates established and emerging cell-based technologies into a coherent map for drug development and, ultimately, for drug regulation.
Researchers affiliated with the MRC Centre for Drug Safety Science have published more than 700 peer-reviewed journal articles that have made significant contribution to the relevant academic disciplines. For more publications from CDSS scientists and their collaborators, please visit our Publications pages.