Conclusion: Flupirtine may lead to severe courses of hepatocellular liver injury and liver failure, especially in women. Monitoring ALT levels may be recommendable for patients receiving flupirtine. Disclosures: Thomas Berg

– Advisory Committees or Review Panels: Gilead, BMS, Roche, Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck; Consulting: Gilead, BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS, Roche, Tibotec; Vertex, Jannssen, Schering Plough, Boehringer Ingelheim, Novartis; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen, Schering Plough, Novartis, Merck, Bayer Florian van Boemmel – Advisory Committees or Review Panels: Roche Pharma; Board Membership: Gilead Sciences; Grant/Research Support: Gilead Sciences, Roche Pharma, BMS; Speaking and Teaching: Gilead Sciences, Roche Pharma, BMS, MSD, Janssen-Cilag, Siemens The followinq people have nothing to disclose: Selleckchem Doramapimod Athanasia Ziagaki, Stephan Boehm, Christin Felkel, Eleni Koukoulioti, Balazs BYL719 mouse Fueloep, Albrecht Boehlig, Adam Herber, Johannes Wiegand Background. Drug compounds have been shown to exert certain effects on pathophysiological

mechanisms involving hepatobiliary transporters in toxic hepatitis (TH) leading to liver dysfunction. Localization and individualized substrate specificities have been proposed to be crucial in TH development. Aims. Evaluate the expression of MDR1, MRP2, MRP3 and BSEP and their association with drug type administered in liver biopsies of patients with TH. Methods. We analyzed data from 16 patients with clinical, biochemical and histopathological diagnosis of TH and 16 without TH (Non-TH). TH patients presented a multidrug-therapy pattern which includes principally immunosuppressive, analgesics and antibiotic drugs. Hepatobiliary transporter expression was analyzed by quantitative real-time PCR and immunohistochemistry. RUCAM score was used to associate a specific expression pattern

for a particular drug. Results. Sixteen patients (7 women and 9 men) with a mean age of 43. 6 years. mRNA expression was significantly lower in TH group than in Non-TH group in MRP2 (p< 0. 03), MRP3 (p< 0. 05) and BSEP (p< 0. 0009). In protein expression MDR1 and MRP2 showed a 100% positivity expression in both groups; however Cytoskeletal Signaling inhibitor in terms of intensity, MDR1 expression was higher in TH group (75%) than in Non-TH group (45%) (P<0. 01), opposite to MRP2 expression which was lower In TH group (31%) than in Non-TH group (45%) (P<0. 01). Regarding MRP3, TH group showed a 56% of positivity expression; meanwhile it was not detectable in Non-TH group. Finally, BSEP presented a lower positivity expression (50%) in comparison to Non-TH group (95%)(Figure). Conclusion. In TH patients there was a down-regulation in BSEP, an increased expression in MRP3 and apparently no change in MRP2 and MDR1 expression.