Drug-induced liver injury is a major problem in drug development, both at preclinical stages as well as during clinical trials.Several methods have been developed to predict DILl with varying degrees of accuracy and applicability.However they are all only partially useful because this problem is inherently challenging.One of the challenges of understanding toxicity in the liver and other organ systems is the innate ability of biological systems to adapt.This adaptation can take many forms-feedback compensation;where the perturbation is sensed by the biological system and similar pathways are upregulated to compensate for the inhibitory function, redundancy;where multiple pathways perform the same function, substrate or product inhibition, etc.