45 It is interesting that a change in alcohol was associated with GGT change independent of a change in steatosis. GGT change was inversely associated with coffee consumption, as found in other studies that were not restricted to patients with HCV.46-48 Furthermore, coffee consumption has previously been found to be associated with improved treatment response and slower disease progression in HALT-C. This association deserves greater scrutiny. Ferritin concentration was strongly associated

with both baseline GGT and with a change in GGT activity. Ferritin is a marker of oxidative stress, which may explain click here the strong correlation with GGT activity.49 HALT-C provided a strong platform for evaluation of prognostic factors in chronic

HCV. Advantages included a large sample size, relatively homogeneous population, careful Protease Inhibitor Library ic50 attention to uniform data collection on a wide variety of variables, and a high patient retention rate. Although GGT activity was strongly associated with treatment response and with disease progression, these results are not necessarily generalizable to all patients with HCV. HALT-C was restricted to patients with advanced liver disease who had not cleared virus with IFN treatment and were motivated to participate in a clinical trial. Furthermore, as new treatments are introduced, GGT may not be as strong a predictor of treatment response. However, given the results of this and other studies, it is likely, that GGT will be associated with poorer response at least as long as IFN-based therapy is used. In conclusion, GGT activity was found to predict treatment response and liver disease outcomes in a large cohort of patients infected

medchemexpress with chronic HCV and advanced fibrotic disease. Although confirmation from other studies is needed regarding the prognostic significance of GGT, results of the current study suggest that greater attention should be given to GGT activity. “
“The human liver reacts to hepatitis C virus (HCV) with a balanced response consisting of host anti-viral and pro-viral activities. To explore these subtle host responses, we used oligonucleotide microarrays to investigate the differential gene expression between two groups of liver samples with high and low HCV loads (>100-fold difference). We identified and validated 26 genes that were up-regulated in the livers with high HCV loads, including transmembrane protease serine 2 (TMPRSS2). Trypsin inhibitors inhibited the infection of Huh7-25-CD81 cells with cell culture-derived HCV (HCVcc) of Japanese fulminant hepatitis 1 isolate (JFH-1) at the post-binding and entry step, and trypsin enhanced HCVcc infection at an early stage of infection. Several major transmembrane serine proteases, in particular furin and hepsin, were detected in Huh7-25-CD81 cells, but TMPRSS2 was not.