Drug Induced Liver Injury (DILI)

By Bart Cobert

The liver is the first stop on the path a drug takes after oral ingestion. From the liver’s “point of view”, drugs are like other exogenous agents and are handled by the liver for excretion. Absorption is largely into the portal system which brings intestinal blood to the liver where transformation and metabolism occur in preparation for elimination (e.g. in the urine, in bile etc.). Metabolism may occur in two phases: Phase I is preparation by oxidation, reduction, hydrolysis and other reactions of the compound for action in Phase II. The second phase occurs in the cytosol and involves reactions  catalyzed by transferase enzymes. The cytochrome P-450 system plays a major role in this.  The study of the P-450 system allows some degree of prediction of possible hepatotoxicity.

Liver toxicity is usually thought of as producing damage to the liver parenchymal cells (hepatocytes) but toxicity can also be produced affecting biliary cells, kupffer cells, fat storing cells etc.