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Models of Drug Induced Liver Injury (DILI) - Current Issues and Future Perspectives

Drug-induced Liver Injury (DILI) is the most common cause of acute liver failure cases in the United States, and also one of the most frequently cited reason of withdrawal of drugs in both preclinical and clinical phases. DILI has been classified as direct (or intrinsic) and idiosyncratic. There are several models that can be useful for studying the mechanisms and pathophysiology of DILI: primary human hepatocytes cultures, cell lines derived from hepatic carcinoma, liver tissue engineering, human pluripotent stem cells derived hepatic cells and animal models. Despite tremendous effort and extensive research, prediction of DILI using in vitro and in vivo models remains very unreliable. The complex network of interactions among genetic, environmental, immune and metabolic factors behind DILI implies that its pathophysiological mechanisms cannot be recapitulated in a single study model. Therefore, the assumption is that addressing safety issues in drug development programs will also include more modeling modalities in the future. Substanital progress has been made in our understanding of DILI using different models, however considerable work remains to be elucidated.

DILI, human hepatocytes cultures, liver tissue engineering, pluripotent stem cells

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