Interplay of Factors Leading to Adverse Drug Reactions in the Liver, A Personal Viewpoint 1

Adverse drug reactions in liver involve formation of a reactive metabolic intermediary of the drug, binding of the intermediary to macromolecules in the cell, notably proteins in the plasma membrane, immunological response to these altered proteins and attack against hepatocytes bearing these altered proteins by immune mechanisms. At each step in this complex process many factors act to enhance or depress drug metabolism, metabolite disposition, macromolecular binding, neoantigen formation, and the cell mediated and humoral immune attack. The extent and direction of each step may be dose dependent but the complexity of the overall mechanism is so immense that predictability of hepatic drug reactions is unlikely in most instances.