We thank the Dana Farber Cancer Institute, Boston, MA, for providing Mcl-1flox/flox mice. In addition, we thank Sandra Heine, Silvia Behnke, Birgit Riepl, and Fian K. Mirea for excellent technical assistance. Additional Supporting Information may be found in the online version of this article. “
“The clinical presentation of Primary biliary cirrhosis (PBC) at the time of liver transplantation (LT) may have changed, due to the long-term use of

ursodeoxycholic acid (UDCA). The aim RG7204 price of this retrospective study was to investigate whether the clinical characteristics of LT recipients with PBC have changed over the years. Of all 421 adults undergoing LT from 1997 to 2012 at our center, we included 85 recipients with PBC into the present study. The 85 recipients were divided into three groups according to the year LT was performed: group 1 (1997–2001, n = 29), group 2 (2002–2005, n = 29) and group 3 (2006–2012, n = 27). There were no significant BEZ235 in vitro differences in sex, recipient age, Model for End-Stage Liver Disease score, updated Mayo risk score for PBC, or liver-related complications except for esophageal varices among the three groups. Patients in group 1 were complicated with esophageal varices less frequently than those in the other two groups. In

older cases, the ratio of explanted liver volume to standard liver volume (ELV/SLV) was significantly higher, and the duration of pre-LT UDCA treatment was significantly shorter. The duration of UDCA treatment was significantly correlated with ELV/SLV. Recent

LT patients were characterized by more frequent portal hypertension and more severe liver atrophy, with longer Raf inhibitor UDCA therapy prior to LT, which might have prevented the somewhat rapid progression of liver failure characterized by hepatomegaly with insignificant fibrosis or portal hypertension. “
“Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors. In vitro and in vivo studies have shown that alisporivir inhibits hepatitis C virus (HCV) replication, and ongoing clinical trials are exploring its therapeutic potential in patients with chronic hepatitis C. Recent data suggest that the antiviral effect is mediated by inhibition of cyclophilin A, which is an essential host factor in the HCV life cycle. However, alisporivir also inhibits mitochondrial permeability transition by binding to cyclophilin D. Because HCV is known to affect mitochondrial function, we explored the effect of alisporivir on HCV protein-mediated mitochondrial dysfunction.