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Surface protein mutations in chronic hepatitis B patients who received hepatitis B vaccine therapy.

ABSTRACT: OBJECTIVE S:The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients. MATERIALS AND METHODS:16 patients received the HBV vaccine and another 16 individuals from the control group did not. The surface gene was amplified and directly sequenced from samples prior to vaccination and six months after the third dose. RESULTS:Only one patient lost HBsAg. 48 and 44 amino acid mutations were found before and after vaccine therapy in the vaccine group respectively, 51 of which (55.4%) occurred in immune epitopes: 5 were in B cell, 21 in T helper (Th), and 25 in cytotoxic T-lymphocyte (CTL) epitopes. In the control group, 35 and 41 amino acid substitutions were found before and after therapy, respectively. 32 (42%) of 76 amino acid changes occurred within immune epitopes. There were no differences in age, gender, and duration of chronicity in both patient and control groups in terms of the frequency and the patterns of mutations. CONCLUSION:In chronic carriers who already had HBsAg variants selected by the host-immune response, any immune stimulation by the vaccine had no effect on the chronic state of these patients or selected any remarkable escape mutants. Newer strategies should be considered based on third generation or the use of DNA vaccines or new adjuvants.

SUBMITTER: Daram M

PROVIDER: S-EPMC4322145 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Surface protein mutations in chronic hepatitis B patients who received hepatitis B vaccine therapy.

Daram Maryam M Montazeri Ghodratollah G Karimzadeh Hadi H Malekzadeh Reza R Mahmoodi Mahmood M Goodarzi Zahra Z Keyvani Hossein H Mirmomen Shahram S Alavian Seyed Moayed SM Roggendorf Michael M Jazayeri Seyed Mohammad SM

Iranian journal of basic medical sciences 20140901 9

<h4>Objective s</h4>The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients.<h4>Materials and methods</h4>16 patients received the HBV vaccine and another 16 individuals from the control group did not. The surface gene was amplified and directly sequenced from samples prior to vaccination and six months after the third dose.<h4>Results</h4>Only one patient l ...[more]

PMID: 25691938

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Project description:The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36.7±8.5 years; 27 males and 8 females) were enrolled in this study. Of the 35 patients, 21 patients received pegylated IFN monotherapy and 14 patients received IFN and adefovir (ADV) combination therapy. We examined the factors associated with reductions in the HBsAg titer of >1.0 log IU/ml from the initial HBsAg titer to the end of treatment and to 24 weeks after treatment. Although 13 patients (37%) had a reduction in HBsAg of >1.0 IU/ml at the end of treatment, it was only maintained to 24 weeks after treatment in 7 patients (20%). The HBV core-related antigen (HBcrAg) titer before treatment was significantly higher in patients with a decrease in HBsAg at the end of treatment than in patients without a decrease in HBsAg (6.56±0.78 vs. 5.30±1.66 log IU/ml, P<0.05). Moreover, an increase in alanine aminotransferase (ALT) of >2 times from baseline occurred significantly more frequently in patients with a decrease in HBsAg (62 vs. 14%, P<0.05). The proportion of patients with a decrease in HBsAg was significantly greater in patients who received IFN monotherapy than in patients who received IFN and ADV combination therapy (43 vs. 29%, P<0.05). The present results revealed that the HBcr antigen titer before therapy and an on-treatment elevation of ALT (indicative of host instruction flare) are important factors associated with a decrease in HBsAg titers after IFN-based therapy. The efficacy of IFN and ADV combination therapy was not apparent in terms of a reduction in the HBsAg titer.

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Surface protein mutations in chronic hepatitis B patients who received hepatitis B vaccine therapy.

Publications

Surface protein mutations in chronic hepatitis B patients who received hepatitis B vaccine therapy.

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