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

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

220

Phase

  • 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

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
Intervention / Treatment
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

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

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

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)

August 1, 2011

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

May 26, 2017

First Submitted That Met QC Criteria

June 20, 2017

First Posted (Actual)

June 21, 2017

Study Record Updates

Last Update Posted (Actual)

June 21, 2017

Last Update Submitted That Met QC Criteria

June 20, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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