Is premarket identification of hepatotoxic drugs and sensitive patients possible based on high-dimensional 'omic...

Idiosyncratic liver toxicity that may lead to post-marketing removal of approved drugs can potentially be explained by the existence of hidden, sensitive subpopulations that are not large enough to affect premarketing toxicity assessments. We consider whether molecular biomarkers of risk and response can be developed to identify sensitive individuals, using classification methods that allow for population heterogeneity represented by characteristics that may not be readily apparent or controlled. If so, drugs that may be hepatotoxic to only a relatively small subpopulation would not be mislabeled as hepatotoxic to the general population and could be prescribed selectively to achieve a maximum health benefit. We outline a possible strategy for identifying individuals who are highly susceptible to drug-related hepatotoxicity and point out the significant challenges.