Impact of Hepatitis B Vaccination on HBs Antigenemia

June 20, 2017 updated by: Amr Shaaban Hanafy, Zagazig University

Impact of Hepatitis B Vaccination on HBsAg Kinetics, Interferon-inducible Protein 10 Level and Recurrence of Viremia

  • HBV is not curable with persistent HBsAg even after the disappearance of HBV DNA.
  • HBsAg > 1000 IU/ml is associated with the risk of virological recurrence and HCC.
  • There is an impaired immune response to HBsAg and HBV vaccine is an easily available, cost-effective, non-harmful method of stimulating immunity.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Persistent HBs antigenemia >1000 IU/ml has a possibility of viral reactivation and hepatoma in 8%; the effect of HBV vaccine on HBsAg was investigated, recurrence of viremia, insulin resistance, and fibrosis regression.

From August 2011 to October 2016, 220 participants with chronic hepatitis B were evaluated at the hepatology clinic-Internal medicine department-Zagazig university-Egypt. They were enrolled after approval of the ethical committee of Zagazig university hospital. Written informed consent was obtained for the interview, clinical evaluation, and blood sampling.

participants were divided into two groups:

  • Inactive carriers (n=100) who were presented with persistent HBsAg, undetected HBV DNA, normal liver enzymes, positive HBeAb and had never been exposed to antiviral therapy.
  • Patients exposed to NAs (n=120): tenofovir 300mg (n=65) or Entecavir 1mg (n=55): A- HBeAg-positive patients (n=60) who received NAs until 1 year after HBe seroconversion and disappearance of HBV DNA with persistent HBsAg B- HBeAg-negative patients (n=60) who received NAs till 3 years after the disappearance of HBV DNA; all showed persistent HBsAg.
  • Exclusion criteria Clinically decompensated liver cirrhosis; hepatocellular carcinoma; other causes of liver disease or mixed causes (excessive alcohol consumption, autoimmune liver disease, immunosuppressive drugs, or who had been infected with hepatitis C virus.

B- Vaccination schedule

  • All the participants had received 30 µg of recombinant HBV vaccine which contains Purified HBsAg produced by recombinant DNA technology (Euvax-B, LG Life Sciences, Korea) intramuscularly in the deltoid region at three different time intervals (0, 1, 6 months). The first dose of the vaccine was initiated 1 year after HBe seroconversion and disappearance of HBV DNA in HBe +ve or 3 years after the disappearance of HBV DNA in HBe -ve patients or immediately after diagnosis of inactive carriers. NAs were stopped three months after the 3rd dose of HBV vaccine
  • Three months after the last dose of vaccine, the participants were evaluated for IP-10 level, the production of protective HBsAb, recurrence of viremia by regular HBV DNA, HBsAg quantification.

Patients who failed to produce HBsAb i.e. HBsAb titer < 10 IU/ml, were given a fourth booster dose of vaccination immediately after confirmation of vaccine non-response.

C- Control Group It included 100 participants who had CHB, with undetectable HBV DNA with persistence of HBsAg and they did not receive HBV vaccine. They were divided into treatment naïve (n=50) and treatment experienced (n=50) who were given tenofovir (n=30) or entecavir (n=20) which were stopped 3 years after HBV DNA disappearance and HBeAg seroconversion and followed for 3 years by evaluation of HBsAg level and HBV DNA every 6 months to detect the natural rate of HBV reactivation.

D- Laboratory analysis It included complete Blood Count, liver function tests, prothrombin time, prothrombin concentration (%), kidney function tests.

  • HCV antibody, HBeAg, HBeAb, HBcAb.
  • Real-time Quantitative PCR for HBV DNA was done at the baseline and then every 6 months after the last dose of HBV vaccine for 3 years (COBAS AMPLICOR HBV MONITOR, with a detection limit of 15 IU/ml; Roche Diagnostic Systems).
  • Insulin resistance was done before initiation of vaccination and 3 months after the last dose of vaccination. It was calculated by HOMA-IR, a value greater than 2 indicates insulin resistance [20].
  • HBV genotyping was performed using INNO-LiPA HBV Genotyping assay; Innogenetics NV, Ghent, Belgium.
  • Determination of HBsAg titer (Elecsys HBsAg II assay, Roche Diagnostics, USA) [21]. It was done before vaccination and 3 months after the last dose of vaccine then every 6 months for 3 years.
  • Anti-HBs antibodies were performed 3 months following the third dose of the vaccine or 3 months after the 4th booster dose. Seroconversion was considered if anti-HBs levels were above 10 IU/ml and non-response if anti-HBs levels were below 10 IU/ml [22].
  • Serum IP-10 levels were determined in serum before vaccination and 3 months after the last dose of vaccine, by a solid-phase sandwich ELISA (Quantikine, R&D Systems, USA) (reference value: 7.8-500 pg/ml).

E- Abdominal ultrasonography participants were examined after 6 hours fast. Criteria of cirrhosis, portal hypertension, and the presence of fatty liver disease were documented.

F- Liver stiffness assessment (LSM) Fibroscan was performed to measure liver stiffness before antiviral therapy and 3 months after the last dose of HBV vaccine, with the number of shots is 10, interquartile range≤ 25%. Liver stiffness 2.5-7 kPa denotes (F0-1), 7-9.5 kPa (F2), 9.5-12.5 kPa (F3), >12.5 kPa denotes cirrhosis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
220

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HBV patients with persistent HBs antigenemia

Exclusion Criteria:

  • decompensated liver cirrhosis
  • hepatocellular carcinoma
  • other causes of liver disease or mixed causes (excessive alcohol consumption,
  • autoimmune liver disease
  • immunosuppressive drugs
  • infection with hepatitis C virus.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: chronic HBV with persistent HBsAg

inactive carriers (n=100). Group II: CHB exposed to nucleos(t)ides (n=120) till 6 months after HBe seroconversion and HBV DNA disappearance in HBeAg positive (n=60) or DNA disappearance in HBeAg negative patients (n=60). All showed persistent HBs antigenemia.

they were given 30 µg of HBV vaccine initiated 6 months after HBe seroconversion and disappearance of HBV DNA.
Biological: HBV vaccine
HBV vaccine which contains Purified HBsAg produced by recombinant DNA technology (Euvax-B, LG Life sciences, Korea) intramuscularly in deltoid region at three different time intervals (0, 1, 6 months).
No Intervention: control group
A control group (n=100) did not receive HBV vaccine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
production of protective HBsAb
Time Frame: three months after the last dose of vaccine
Current treatment by NAs may suppress HBV replication but cannot completely eradicate the virus due to the systemic immune tolerance or exhaustion. HBV vaccine may enhance the immunity against HBsAg and may be an efficient immunotherapy in chronic HBV.
three months after the last dose of vaccine

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
impact on Insulin resistance, fibrosis regression
Time Frame: 3 month after the last dose of vaccination
study of the possibility of improving insulin resistance and degree of fibrosis
3 month after the last dose of vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zagazig University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 21, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 3777

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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