Anti-HCV Core Protein Polyclonal antibody

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have potent anti-HCV effects but may provoke resistance-associated variants (RAVs). In this study, we assessed the characteristics of these RAVs and explored efficacious anti-HCV reagents using recombinant HCV with NS5A from a genotype 1b strain. We replaced the NS5A of JFH1 with that of Con1 (JFH1/5ACon1) and introduced known NS5A inhibitor resistance mutations (L31M, L31V, L31I and Y93H) individually or in combination. Susceptibilities against anti-HCV reagents were also investigated. RAVs with Y93H exhibited high extracellular core antigen levels and infectivity titers. Variants with any single mutation showed mild to moderate resistance against NS5A inhibitors, whereas variants with double mutations at both L31 and Y93 showed severe resistance. The variants with mutations exhibited similar levels of susceptibility to interferon (IFN)-alpha, IFN-lambda 1, IFN-lambda 3 and Ribavirin. Variants with the Y93H mutation were more sensitive to protease inhibitors compared with JFH1/5ACon1. In conclusion, the in vitro analysis indicated that the Y93H mutation enhanced infectious virus production, suggesting advantages in the propagation of RAVs with this mutation. However, these RAVs were susceptible to protease inhibitors. Thus, a therapeutic regimen that includes these reagents is a promising means to eradicate these RAVs.

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95% CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95% CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95% CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95% CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95% CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95% CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95% CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95% CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95% CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found. CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship. (C) 2013 Baishideng. All rights reserved.