Hepatotoxicity
Hepatotoxicity (from hepatic toxicity) is chemical-driven liver damage. One of the main causes of hepatotoxicity in western countries is acetaminophen (paracetamol) poisoning. Hepatic damage can sometimes be detected at advanced stages by the typical yellow skin (jaundice) that arises from defective bilirubin liver metabolism. For earlier stages, there are a number of convenient liver function tests.Many common drugs are metabolised by the liver in significant amounts. This, together with its role as first filter of blood loaded with substances absorbed from the gut, makes hepatotoxicity one of the main concerns of pharmaceutical companies in their research for new drugs. All lead optimisation cascades must deal in some way with the issue of hepatic toxicity. An especially thorny issue is entero-hepatic recirculation. Entero-hepatic recirculation is the excretion of the drug (or a metabolite of it) through the bile to be re-absorbed in the gut and sent again to the liver along the portal vein, so the excretion-reabsortion cycle can start again. Due to this process, some molecules not too toxic as such may become extremely destructive as they can reach unexpectedly high hepatic concentrations, or prolonged permanence in the entero-hepatic system.