Biomarkers of drug-induced liver injury

Yong Zhou, Shizhen Qin, Kai Wang

Institute for Systems Biology, Seattle, WA, USA

Abstract: The liver plays a central role in metabolizing xenobiotics; therefore, it is highly susceptible to toxicity from these chemicals. Certain drugs, when taken in overdose and sometimes even when used within therapeutic range, may cause injury to the organ. Drug-induced liver injury is now not only a leading cause of acute liver failure in the US, but is also a leading reason for discontinuation of drugs in development and for regulatory actions against previously approved drugs. The current clinical biomarkers to detect and monitor drug-induced liver injury are inadequate in terms of sensitivity and/or specificity, prompting the need for more informative biomarkers. The development of high throughput proteomics, genomics, and metabolomics technologies has the potential to fulfill such demand. The discipline of systems toxicology may add to our understanding of perturbed xenobiotic networks, which may lead to network-specific surrogate markers and therapeutic means to stop or reverse xenobiotic-induced liver injury.

Keywords: hepatotoxicity, idiosyncratic, metabolomics, genomics, proteomics, microRNA, systems toxicology