These studies highlight the complexity of targeting insulin sensitivity to tackle the primary obstacles encountered in treating type 2 diabetes and obesity, namely insulin and leptin resistance. Further studies clarifying the cross-talk between liver metabolism and central regulation of appetite and energy expenditure are clearly warranted. The authors thank Dr. P. Bhathal,

find more (an experienced liver histopathologist, Melbourne Pathology, Melbourne, Australia) for reviewing the H&E-stained sections of the liver. We also thank Dr. Anne Johnston for editing of the manuscript. Additional Supporting Information may be found in the online version of this article. “
“Most direct-acting antivirals (DAAs) that are being developed as therapy against hepatitis C virus target the NS3/4A protease, the NS5A

protein, and the NS5B polymerase. The latter enzyme offers different target sites: the catalytic domain for nucleos(t)ide analogues as well as a number of allosteric sites for nonnucleos(t)ide inhibitors. Two NS3/4A protease inhibitors have been approved recently, and more than 40 new NS3/4A, NS5A, or NS5B inhibitors are in development. These agents can achieve very high cure see more rates when combined with pegylated interferon-β and ribavirin and

show promising clinical results when administered in all-oral combinations. In addition to the more canonical drug targets, new alternative viral targets for small-molecule drug development are emerging, such as p7 or NS4B and viral entry. Future research will need to define well-tolerated and cost-effective DAA combinations that provide the highest rates of viral eradication in all patients (including those with advanced liver disease), MCE公司 the broadest spectrum of action on viral genotypes showing minimal or no clinical resistance, and the shortest treatment duration. (Hepatology 2013) For more than a decade, the standard treatment of chronic hepatitis C virus (HCV) infection has been based on the combination of pegylated interferon-β (PEG-IFN) and ribavirin (RBV) administered for 24 or 48 weeks. These regimens eradicate infection in 40% to 50% of treated patients with genotype 1 (HCV-1) infection and 80% of treated patients with genotype 2 (HCV-2) and 3 (HCV-3) infection. In addition, PEG-IFN/RBV regimens are poorly tolerated and contraindicated in a high percentage of patients. In order to address the shortcomings of PEG-IFN/RBV therapy, new direct-acting antivirals (DAAs) are being developed that target specific HCV functions.