For community health centers: The Health Resources and Services Administration should Opaganib provide adequate resources to federally funded community health facilities for provision of comprehensive viral hepatitis services. For other settings that target at-risk populations, such as sexually transmitted disease and HIV clinics, shelter-based programs, and mobile health units: The Health Resources and Services Administration and CDC should provide resources and guidance to integrate comprehensive viral hepatitis services into those settings that serve

high-risk populations. The IOM committee believes that implementation of these and other recommendations in its report would lead to reductions in new HBV and HCV infections, fewer medical complications and deaths as a result of these viral infections of the liver, and lower total health costs. Advances will be needed: in knowledge and awareness about chronic viral hepatitis, in improvement of hepatitis B vaccine coverage, in improvement and EPZ015666 price better integration of viral hepatitis services, and in improvement of estimates of the burden of disease for resource-allocation purposes. The authors thank the members of the IOM’s

Committee on Prevention and Control of Viral Hepatitis Infections: Harvey J. Alter, Margaret L. Brandeau, Daniel R. Church, Alison A. Evans, Holly Hagan, Sandral Hullett, Stacene R. Maroushek, Randall R. Mayer, Brian J. McMahon, Martín Jose Sepúlveda, Samuel So, David L. Thomas, and Lester N. Wright. “
“Protease-activated receptor (PAR) 2 is a G-protein–coupled receptor that is activated after proteolytic cleavage by serine proteases, including mast cell tryptase and activated coagulation factors. PAR-2 activation augments inflammatory and profibrotic pathways through the induction of genes encoding proinflammatory cytokines and

extracellular matrix proteins. Thus, PAR-2 represents an important interface linking coagulation and inflammation. PAR-2 is widely expressed in cells of the gastrointestinal tract, including hepatic stellate selleck cells (HSCs), endothelial cells, and hepatic macrophages; however, its role in liver fibrosis has not been previously examined. We studied the development of CCl4-induced liver fibrosis in PAR-2 knockout mice, and showed that PAR-2 deficiency reduced the progression of liver fibrosis, hepatic collagen gene expression, and hydroxyproline content. Reduced fibrosis was associated with decreased transforming growth factor beta (TGFβ) gene and protein expression and decreased matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinase 1 gene expression. In addition, PAR-2 stimulated activation, proliferation, collagen production, and TGFβ protein production by human stellate cells, indicating that hepatic PAR-2 activation increases profibrogenic cytokines and collagen production both in vivo and in vitro.