Immunoallergic Drug-Induced Liver Injury in Humans

Abstract

No conclusive data exist that define the mechanisms of idiosyncratic drug-induced liver injury (DILI) in humans; therefore, we are forced to speculate based on their clinical characteristics. The major characteristics are most easily explained by an immune mechanism. Many cases of idiosyncratic DILI tend to have a longer delay in onset and sometimes do not occur rapidly on rechallenge. These instances of DILI have been attributed to metabolic idiosyncrasy. However, these characteristics may also reflect an autoimmune mechanism, and most drugs that cause idiosyncratic DILI are also associated with various types of other autoimmune reactions. A characteristic feature of the immune system is that different individuals respond differently to the same immunogen. In some cases, a drug can induce an immune response to a reactive metabolite acting as a hapten; in others, the response is against a native protein, which leads to an autoimmune reaction. This is likely responsible for the interindividual differences in susceptibility and outcome noted in human DILI.