This discovery complements growing evidence that Hh signaling guides repair of chronically injured livers, and it suggests that common mechanisms mediate fetal liver development and repair of adult liver injury. Therefore, progress in delineating how Hh-responsive mechanisms regulate liver growth and C59 wnt mw development might help to unravel conserved mechanisms that control regeneration
of injured livers in adults. Such knowledge has important implications for patients with various types of acute and chronic liver damage. The authors thank Dr. Xiaoling Wang (Gastroenterology, Duke University) and Dr. Gregory Michelotti (Anesthesiology, Duke University) for technical assistance, and Dr. Jiawen Huang (Gastroenterology, Duke University) for animal care assistance. The authors thank W. C. Stone (Gastroenterology, Duke University) for his administrative support
to this work. Additional Supporting Information may be selleck compound found in the online version of this article. “
“The aim of this study was to determine the safety and potential efficacy of B-cell depletion with the anti-CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA). This open-label study enrolled six patients with PBC and incomplete responses to UDCA to be treated with 2 doses of 1000 mg rituximab separated by 2 weeks and followed for 52 weeks. The primary endpoints were safety and changes in B-cell function. Anidulafungin (LY303366) Two patients received only 1 dose of rituximab, one due to activation of latent varicella and the other due to a viral upper respiratory infection. Serum levels of total IgG, IgM, and IgA as well as anti-mitochondrial
autoantibodies (AMAs) IgA and IgM decreased significantly from baseline by 16 weeks and returned to baseline levels by 36 weeks. Stimulation of B cells with CpG produced significantly less IgM at 52 weeks after treatment compared with B cells at baseline. In addition, transient decreases in memory B-cell and T-cell frequencies and an increase in CD25high CD4+ T cells were observed after treatment. These changes were associated with significant increases in mRNA levels of FoxP3 and transforming growth factor-β (TGF-β) and a decrease in tumor necrosis factor-α (TNF-α) in CD4+ T cells. Notably, serum alkaline phosphatase levels were significantly reduced up to 36 weeks following rituximab treatment. Conclusion: These data suggest that depletion of B cells influences the induction, maintenance, and activation of both B and T cells and provides a potential mechanism for treatment of patients with PBC with an incomplete response to UDCA. (HEPATOLOGY 2012) Primary biliary cirrhosis (PBC) is a female-predominant, organ-specific autoimmune disease characterized by nonsuppurative destructive cholangitis of the intrahepatic bile ducts.