Efficacy of tenofovir disoproxil fumarate therapy in nucleoside-analogue naive Iranian patients treated for chronic hepatitis B

Background: Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB). Objectives: To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB. Patients and Methods: The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability. Results: In all, 93 patients (64.5 hepatitis B e antigen HBeAg-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia. Conclusions: The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF. © 2015, Kowsar Corp

Evaluating novel adjuvant systems for the induction of humeral and cellular immune responses in hepatitis C virus capsid protein immunization

Background: As a worldwide problem, hepatitis C Virus (HCV) infection similar to HIV and vaccine studies on HCV is among the hottest research topics in the field. Such a vaccine should elicit strong humeral and cellular responses against HCV antigens (Ags). The major aim of the present study was to compare and optimize the responses against HCV core protein (HCVcp) immunization formulated in novel human compatible adjuvants. Materials and Methods: BALB/c mice were immunized by HCVcp, purified in native conditions and in different adjuvant formulation in separate following groups: Ag+CpG, Ag+M720 (Montanide ISA 720), Ag+F127 (Pluronic acid) and cocktails of Ag+F127+CpG and Ag+M720+CpG. ELISA-based assays were used to analyze IgG, cytokine and CTL responses. Results: The M720 (+CpG) immunized mice developed the highest HCVcp-specific titrations of total IgG,IgG1, 2a, 2b, and that of IFN-γ and IL-4 cytokines. HCVcp-specific-CTLs against relevant MHC class I peptides were detected only for Ag+M720+CpG, Ag+M720, and Ag+CpG groups, could be blocked by antimouse-CD8 antibodies and were stable for one year post-immunization. Conclusions: The M720 formulation of HCVcp (with a synergistic effect by inclusion of CpG) induces equally strong Th1/Th2 responses and stable CTLs