Improved Prevention of Perinatal Hepatitis B Transmission

June 16, 2010 updated by: Hadassah Medical Organization

The Employing of the Bio-Hep-B PreS1/PreS2/S Hepatitis B Virus (HBV) Vaccine in New Born Babies From HBV Positive Palestinian Mothers

Impaired activity of Natural Killer (NK) cells has been proposed as a mechanism contributing to viral persistence in Hepatitis C Virus (HCV) infection. NK cells display anti-fibrotic activities by killing activated hepatic stellate cells (HSCs) that have lost the self-recognition marker; Major Histocompatibility (MHC) class I. Determining the down-expressed genes on NK cells necessary for their anti-fibrotic activity was never studied previously. This will allow us to study their role fully in phagocytosis process as well as their interaction of HSCs and therefore manipulating these genes using molecular techniques. Exploring the cellular functions of these genes will highlight their involvement in the progression of liver fibrosis and could be used as a therapeutic tool for preventing the disease.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Lymphocyte/Hepatic stellate cells (HSCs) interactions via adhesion and phagocytosis are mediated as well as affected among others by Leptin, Endocannabinoids (CB) receptors, adiponectin, progesterone as well as by number of CD8 and NK related adhesion/phagocytosis candidate genes. Those pathways may explain the impaired activity of NK cells in Hepatitis C Virus (HCV)cirrhotic cases.

In this perspective, we propose the following specific aims:

  1. To confirm by repeated gene arrays the pro/anti-fibrotic genes expressed by NK and CD8 lymphocyte-subsets in human healthy volunteers and patients with HCV cirrhosis. Then to explore the same issue of lymphocyte gene array (NK and CD8 cells) in naïve and carbon tetrachloride fibrosis model in mice. Then to support results by the Real Time PCR and conduct bio-informatics assessments of results.
  2. Evaluate the role of Leptin, CB receptors and adiponectin in the lymphocyte/HSCs phagocytosis process. This would be tested both by in-vitro and in-vivo settings using cell cultures and knock-out mice (CB2-/-, Adiponectin-/- and leptin-/-Ob/Ob). The use of lymphocyte adoptive transfer model with immune manipulations will guide us for a specific functional role of each target gene in the specific lymphocyte subset.
  3. To evaluate how lymphocyte/HSC phagocytosis process affected by other CD8 and NK related gene candidates extrapolated from the results of earlier aims (see preliminary data). Suggested genes are including: Immune synapse genes (CHST13 and NLGN4X) to obtain the expected anti-fibrotic response. Genes with HSCs phagocytotic activity that is providing possible pathways for the HCV related escape from the expected anti-fibrotic response and eventually pro- fibrotic consequences (AIF1, CHST13, hnRPL). Killer cell lectin-like receptor subfamily C, member 2 (NKG2C; CD159c) is down expressed over HCV related CD8 cells suggesting a decrease of HSCs killing by the CD8 cells. Progestin & adipoQ receptor family member IV (PAQR4): Progesterone and adipoQ receptors are down-expressed over HCV related CD8 cells. Adiponectin is anti-fibrogenic mediator and is a candidate as PAQR4 ligand. When PAQR4 receptor is down- regulated in CD8 cells, it is suggested that this would be a mechanism for immune impairment. Also, Moreover, Progesterone and adipoQ receptors down- expression is supporting our mice animal model results that pregnancy caused progression of hepatic fibrogenesis associated with increased CD8 subsets and NK-T cells. We are going to evaluate the specific effect in the phagocytosis process.
  4. To evaluate if HCV by itself or HCV related proteins are directly responsible for the NK related impairment. Transgenic mice for the HCV envelop proteins will be used to assess alterations of lymphocyte subsets and phagocytosis ability.

The expected results will extend the knowledge of hepatic fibrogenesis in particular but may provide more application in general immunology. Therefore, expected results will be potentially a new target for anti-fibrotic designs and possibly in other medical conditions. Not only liver cirrhosis will be potentially prevented following anti-fibrotic therapies but also the hepatocellular carcinoma

Study Type

Interventional

Enrollment (Anticipated)

6343

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center

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

No older than 40 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All Hepatitis B s Antigen (HBsAg) positive pregnant women attending the centers will be suggested to participate in the study and therefore provided with all information needed

Exclusion Criteria:

  • Co-infection with HIV
  • Mothers with immune suppression

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Co-infection with Hepatitis D and HIV.
Time Frame: 3 month
3 month

Collaborators and Investigators

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

Sponsor

Hadassah Medical Organization

Investigators

  • Principal Investigator: Rifaat Safadi, M.D, Hadassah Medical Organization

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

September 1, 2010

Primary Completion (Anticipated)

March 1, 2011

Study Completion (Anticipated)

September 1, 2013

Study Registration Dates

First Submitted

May 25, 2010

First Submitted That Met QC Criteria

May 27, 2010

First Posted (Estimate)

May 28, 2010

Study Record Updates

Last Update Posted (Estimate)

June 17, 2010

Last Update Submitted That Met QC Criteria

June 16, 2010

Last Verified

January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0509-08-HMO

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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