Immune drug-induced liver disease and drugs

Abstract

Idiosyncratic drug-induced liver injury (DILI) represents a major public health concern and impediment to drug development. The mechanisms of DILI are not completely understood; both non-immune and immune mediated mechanisms have been proposed. Non-immune mediated mechanisms including direct damage to hepatocytes, mitochondrial toxicity, interference with transporters, and alteration of bile ducts, are well known to be associated with drugs such as acetaminophen and diclofenac; whereas immune-mediated mechanisms involving activation of both adaptive and innate immune cells, and the interactions of these cells with parenchymal cells have been proposed. A variety of hypotheses for immune-mediated DILI and the roles of liver immune cells in the development of DILI are discussed with respect to recent scientific advances. Additionally, understanding the mechanisms of how circulating leukocytes home to the liver upon injury, and their nature and location in the liver, is critical for the pathogenesis of DILI. Continuous research in understanding the molecular and cellular mechanisms of DILI and identifying risk factors will provide an opportunity to develop better test systems for the diagnosis, prediction, and prevention of DILI.