<2 y vs. >2 y; a p< 0.005 by unpaired t-test Disclosures: The following people have nothing to disclose: Jaime C. Silva, Stacey S. Beer, Ursula G. Kyle, Mariana Treviño Ramos, Jennifer Cytoskeletal Signaling inhibitor L. Lusk, Ryan Himes, Moresh-war Desai, John A. Goss, Jorge Coss-Bu “
“Recent progress in

research on drug-induced liver injury (DILI) has been determined by key developments in two areas. First, new technologies allow the identification of genetic risk factors with improved sensitivity, specificity, and efficiency. Second, new mechanistic concepts of DILI emphasize the importance of unspecific “downstream” events following drug-specific initial “upstream” hepatocyte injury and of complex interactions between environmental and genetic risk factors. The integration of genetic and mechanistic concepts is essential for current research approaches, and genetic studies of DILI now focus on targets that affect the

function and transcriptional regulation of genes relating not only to drug metabolism but also to human leukocyte antigens (HLAs), cytokines, oxidative stress, and hepatobiliary transporters. Risk factors affecting unspecific downstream mechanisms may be identified using pooled DILI cases caused by various drugs. The Vemurafenib in vitro power to detect variants that confer a low risk can be increased by recruitment of strictly selected cases through large networks, whereas controls may also be obtained from genotyped reference populations. The first genomewide

studies of DILI identified HLA variants as risk factors for hepatotoxicity associated with flucloxacillin and ximelagatran, and their design has defined a new standard for pharmacogenetic studies. From a clinical and regulatory point of view, there is a need for genetic tests that identify patients at increased hepatotoxic risk. However, DILI is a rare complex disease, and pharmacogenetic MCE公司 studies have so far not been able to identify interactions of several risk factors defining a high population-attributable risk and clinically relevant absolute risk for DILI. (HEPATOLOGY 2010) Pharmacogenetics deals with genetic variation and its impact on how individual patients respond to drugs. Similar to the study of other drug-induced diseases, the principal aims of pharmacogenetic research on drug-induced liver injury (DILI) are an elucidation of hepatotoxic mechanisms and the prediction of DILI in individual patients. Expectations linked to genetic research are high at the end of a decade that has heralded a new era of genetics-based personalized medicine. Major technological and methodological advances in the field of genetics during the past few years have made the conduct of genomewide association studies (GWAS) possible and now allow robust and efficient identification of common variants that confer only a small risk of disease (“low-risk variants”).