ABSTRACT
Immune-mediated injury plays a primary or secondary role in many forms of drug-induced
liver injury (DILI) (1,2). This mechanism of DILI is suggested clinically by the presence of
features of systemic immune activation such as concomitant fever, rash, atypical lymphocytes,
and/or eosinophilia. When drug rechallenge occurs, immune-mediated mechanisms of DILI
are confirmed by the development of an accelerated onset of equally or more severe liver injury
indicating the presence of immunological memory, the signature of an adaptive
immune response (1,3). In many such cases, hepatic drug metabolism has been found
to produce reactive metabolites that haptenate or alkylate self proteins which in turn
elicit adaptive immune responses and associated liver injury in genetically susceptible
individuals (2,4-6). More recently, it has been recognized that drugs that directly injure
hepatocytes may also trigger innate immune responses apparently directed at damaged
hepatocytes (2,7,8).
