Drug induced liver injury (DILI) can result in a build-up of oxidative stress in hepatocytes,causing them to become stressed and die. Experiments using APAP as a model of DILI show an initial pattern of centrilobular damage which gets amplified by stressed cells communicating through gap junctions and the activation of the immune system in response to this injury. While hepatocyte proliferation takes place to combat liver mass loss, higher doses could still be lethal to the tissue. This talk will try to address the question of what tips the balance, that the same set of cell behaviors that are needed for tissue survival can also lead to widespread tissue death in some other situations? To answer this, I will discuss results of a computational model based on the competing biological processes of hepatocyte proliferation, necrosis and injury propagation. This model sheds light on the evolution of tissue damage or recovery and predicts the potential for divergent fates given different rates of the parameters related to these three processes.
