Chronic Hepatitis B VirusLiNKeB2NCT06853886
Gene Discovery in CHB Patients to Identify Unknown Pathways That Lead to B and NK Cell Deregulation
A study testing blood sample HBV patient and blood sample healthy volunteers in people with Chronic Hepatitis B Virus, run by University Hospital, Limoges at 3 sites in France.
Trial summary
Natural Killer (NK) and B cell immune responses occur during the early stages of infection and are essential to eradicate it. Yet, chronic hepatitis B (CHB) infection occurs because the antiviral immune response is insufficient. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Hepatitis B Virus
- What is being tested?
- blood sample HBV patient and blood sample healthy volunteers
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 3 sitesFrance
- Study dates
- 12 Aug 2025to 1 Oct 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female, age ≥18 years old
- HBV infection or chronic HBV infection untreated or treated with a nucleoside or nucleotide analog
- Willing and able to provide written informed consent
- Affiliated with a social securityregimen
- Healthy volunteer must meet all of the following inclusion criteria to be eligible for participation in this study:
- Male or female, age between 18 and 80 years
- Willing and able to provide written informed consent
Who cannot join
- Co-infection with HCV, HIV or HDV (or HBV for healthy volunteer)
- Acute hepatitis in the year preceding recruitment
- Other liver diseases : alcohol, obesity (BMI>30), diabetes, metabolic syndrome (dyslipidemia and/or known hypertension) - Underlying immunological or cancerous diseases
- Patient with a disability that prevents him/her from fully understanding the requirements of the trial - Patient under court protection, guardianship or curatorship
- Pregnant or breast-feeding women.
- Secondary exclusion criteria:
Show all 10Show fewer
- A healthy volunteer whose vaccination status does not match that expected on the basis of serological results
- Positive blood pregnancy test on inclusion
- Positive HCV, HIV or HDV test in a patient
- Positive HBV, HCV, HIV or HDV test in a healthy volunteer
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites, 3 recruiting
- Recruiting
Centre d'Investigation Clinique
Limoges, 87042
Fabienne MARIAUD, MD
- Recruiting
Limoges University Hospital
Limoges, 87042
Véronqiue LOUSTAUD-RATTI, MD
- Recruiting
Hospice civils de Lyon
Lyon, 69004
Fabien ZOULIM, MD
About this study
Natural Killer (NK) and B cell immune responses occur during the early stages of infection and are essential to eradicate it. Yet, chronic hepatitis B (CHB) infection occurs because the antiviral immune response is insufficient. In both NK and B cell studies we will explore the genetic alterations that occur during the varied chronic stages of the disease. We believe that our findings will allow us to understand the molecular signature of NK and B cells in the context of HBV infection.
Read the detailed description
Thanks to past ANRS funding we showed that both B and NK cells are dysfunctional in Hepatitis B virus (HBV) in in vitro human models and validated in patients with chronic infection. We observed that B cells responses by Toll Like Receptor 9 (TLR9) were inhibited by the HBV viral protein HBsAg. We noted the loss of TLR9 expression on all B cell subsets by HBV was mediated by loss of its promoter activity by blocking the phosphorylation of the transcription factor CREB (pCREB). Furthermore, B cell-TLR9 mediated responses such as proliferation and cytokine production were abrogated in CHB patients. For NK cells we demonstrated several significant changes in their receptor expression, loss of cytokines IFN γ, MIP1a and cytotoxicity compared to healthy donors. However, for both NK and B cell dysfunction the molecular basis and signaling pathway of this phenomenon are poorly characterized and whether this state can be reversed, a question of therapeutic importance, is unknown. We hypothesize that several molecular changes occur in NK cells from CHB patients that depend on altering the mTOR pathway by HBV and more specifically by HBsAg. Together our results from this proposal should define the genetic signatures that lead to B and NK cell function and will contribute to our understanding on immune dysfunction by HBV. In both NK and B cell studies we will explore the genetic alterations that occur during the varied chronic stages of the disease. This can only be investigated in patients including all clinical stages of CHB.
- Conditions
- Chronic Hepatitis B Virus
- Being tested
- blood sample HBV patient, blood sample healthy volunteers
- Keywords
- HBV, NK celles, TLR9, B cells
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sample HBV patientOther
During a boold sample at only one follow up visit:
- 3 tubes EDTA 10 ml per patient
- 1 tube "Paxgene" 1ml
- 2 dry tube per patient
blood sample healthy volunteersOther
- 3 tubes EDTA ideally age and sex matched to CHB patient.
- 1 tube "Paxgene" 1ml
- 2 dry tube
| Study group | Role | What they receive |
|---|---|---|
| HBV patient | Other | a blood sample is done during a follow-up visit Receives: Other: blood sample HBV patient |
| healthy volunteers | Other | a blood sample Receives: Other: blood sample healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
RNA sequencing of B cells from CHB patients at different stages, description of their molecular signature
Measured: At inclusion, day 0
Secondary outcomes (1)
RNA sequencing of NK cells from CHB patients at different stages, description of their molecular signature (protein expression measured by flow cytometry)
Measured: At inclusion, day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2025
- Study start12 Aug 2025
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis B VirusStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Collaborators
- National Agency for Research on AIDS and Viral Hepatitis (ANRS)
- Responsible party
- Sponsor
- Investigators
- Paul CARRIER, MD, Principal investigator, University Hospital, Limoges
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06853886
- Sponsor's protocol ID
- 87RI24_0023 (LiNKeB2)
- Acronym
- LiNKeB2
- Status last verified
- Sep 2025
- First submitted
- 25 Feb 2025
- Last updated
- 20 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene Discovery in CHB Patients to Identify Unknown Pathways That Lead to B and NK Cell Deregulation
- ClinicalTrials.gov ID
- NCT06853886
- Acronym / sponsor ID
- LiNKeB2 / 87RI24_0023 (LiNKeB2)
- Conditions
- Chronic Hepatitis B Virus
- Keywords
- HBV, NK celles, TLR9, B cells
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Collaborators
- National Agency for Research on AIDS and Viral Hepatitis (ANRS)
- Study start
- 12 Aug 2025 (actual)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 3 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Natural Killer (NK) and B cell immune responses occur during the early stages of infection and are essential to eradicate it. Yet, chronic hepatitis B (CHB) infection occurs because the antiviral immune response is insufficient. In both NK and B cell studies we will explore the genetic alterations that occur during the varied chronic stages of the disease. We believe that our findings will allow us to understand the molecular signature of NK and B cells in the context of HBV infection.
Detailed description
Thanks to past ANRS funding we showed that both B and NK cells are dysfunctional in Hepatitis B virus (HBV) in in vitro human models and validated in patients with chronic infection. We observed that B cells responses by Toll Like Receptor 9 (TLR9) were inhibited by the HBV viral protein HBsAg. We noted the loss of TLR9 expression on all B cell subsets by HBV was mediated by loss of its promoter activity by blocking the phosphorylation of the transcription factor CREB (pCREB). Furthermore, B cell-TLR9 mediated responses such as proliferation and cytokine production were abrogated in CHB patients. For NK cells we demonstrated several significant changes in their receptor expression, loss of cytokines IFN γ, MIP1a and cytotoxicity compared to healthy donors. However, for both NK and B cell dysfunction the molecular basis and signaling pathway of this phenomenon are poorly characterized and whether this state can be reversed, a question of therapeutic importance, is unknown. We hypothesize that several molecular changes occur in NK cells from CHB patients that depend on altering the mTOR pathway by HBV and more specifically by HBsAg. Together our results from this proposal should define the genetic signatures that lead to B and NK cell function and will contribute to our understanding on immune dysfunction by HBV. In both NK and B cell studies we will explore the genetic alterations that occur during the varied chronic stages of the disease. This can only be investigated in patients including all clinical stages of CHB.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HBV patient | Other | Other: blood sample HBV patienta blood sample is done during a follow-up visit |
| healthy volunteers | Other | Other: blood sample healthy volunteersa blood sample |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female, age ≥18 years old
- HBV infection or chronic HBV infection untreated or treated with a nucleoside or nucleotide analog
- Willing and able to provide written informed consent
- Affiliated with a social securityregimen
- Healthy volunteer must meet all of the following inclusion criteria to be eligible for participation in this study:
Key exclusion criteria (10 listed)
- Co-infection with HCV, HIV or HDV (or HBV for healthy volunteer)
- Acute hepatitis in the year preceding recruitment
- Other liver diseases : alcohol, obesity (BMI>30), diabetes, metabolic syndrome (dyslipidemia and/or known hypertension) - Underlying immunological or cancerous diseases
- Patient with a disability that prevents him/her from fully understanding the requirements of the trial - Patient under court protection, guardianship or curatorship
- Pregnant or breast-feeding women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sample HBV patientDuring a boold sample at only one follow up visit: * 3 tubes EDTA 10 ml per patient * 1 tube "Paxgene" 1ml * 2 dry tube per patient | Other | HBV patient |
| blood sample healthy volunteers* 3 tubes EDTA ideally age and sex matched to CHB patient. * 1 tube "Paxgene" 1ml * 2 dry tube | Other | healthy volunteers |
Primary outcome
RNA sequencing of B cells from CHB patients at different stages, description of their molecular signature
Time frame: At inclusion, day 0
1 secondary outcome
RNA sequencing of NK cells from CHB patients at different stages, description of their molecular signature (protein expression measured by flow cytometry)
Time frame: At inclusion, day 0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul CARRIER, MD principal investigator
University Hospital, Limoges
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sample HBV patient and blood sample healthy volunteers in people with Chronic Hepatitis B Virus, run by University Hospital, Limoges at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paul CARRIER, MD (+335 55 05 80 22, paul.carrier@chu-limoges.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RNA sequencing of B cells from CHB patients at different stages, description of their molecular signature (time frame: At inclusion, day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2026.