Blockade of HMGB1-RAGE interaction has been shown to effectively reduce liver damage upon acute injury.14, 15, 49 Unfortunately, Hmgb1−/− mice die at birth50 and, hitherto, no conditional Hmgb1−/− mouse has been established to test whether HMGB1 ablation in see more the Mdr2−/− mouse phenocopies the dKO liver phenotype. Furthermore, it will be of great interest to correlate the expression of RAGE and the abundance of its ligands, in particular HMGB1, with the severity of disease and its clinical outcome in different human liver disorders, and to prove the concept that pharmacological inhibition of RAGE

signaling represents a novel strategy for the prevention of HCC development during early stages of liver injury. We thank Tine Bauer, Angelika Krischke, and Sandra Prokosch for technical support, Prof. George Yeoh (University of Western Australia) and Janina Tirnitz-Parker for BMOL cells, and Valentina Factor (NIH) for the A6 antibody. Additional Supporting Information may be found in the online version of this article. “
“Fafi-Kremer S, Fofana I, Soulier E, Carolla P, Meuleman P, Leroux-Roels G, et al. Viral entry and escape from antibody-mediated neutralization http://www.selleckchem.com/products/chir-99021-ct99021-hcl.html influence hepatitis

C virus reinfection in liver transplantation. J Exp Med 2010;207:2019-2031. (Reprinted with permission.) End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the

liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms Ribonucleotide reductase of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft. Recurrent hepatitis C after orthotopic liver transplantation (OLT) for hepatitis C–associated end-stage liver disease or hepatocellular carcinoma is a vexing clinical problem. Rapid reinfection of the liver graft by hepatitis C virus (HCV) particles in the blood is nearly universal, and the ensuing disease often runs an accelerated course quickly progressing to graft cirrhosis and retransplantation or death.1 In contrast to hepatitis B, no passive immunoprophylaxis is currently available.