Chronic Hepatitis bRES-HBVNCT06047093
Fine Needle Aspiration (FNA) Evaluation of the Intrahepatic HBV Reservoir and Its Immunological Characteristics in Chronically HBV-infected Patients
A study testing Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Creation of a serum biobank and FNA feasibility and acceptability questionnaire in people with Chronic Hepatitis b, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Two hundred and ninety-six million people worldwide are chronically infected with the hepatitis B virus (HBV), with around 750,000 deaths each year linked to the development of cirrhosis or hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis b
- What is being tested?
- Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Creation of a serum biobank and FNA feasibility and acceptability questionnaire
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 8 Mar 2024to 8 Mar 2030
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (≥ 18 years of age)
- Patients chronically infected with hepatitis B virus at any stage of infection
- Nucleoside Analogues-treated or untreated
- Co-infected or not with HDV
- Included in the prospective CirB-RNA study (part of the CirB-RNA university research program) (ID-RCB : 2018-A02558-47, NCT03825458)
- Patient informed of the study and having signed a consent form
Who cannot join
- Pregnant, parturient or breast-feeding women,
- Patients with decompensated cirrhosis
- Patients with hepatocellular carcinoma (suspected or proven),
- Liver transplant patients (even if liver transplantation for HBV),
- Patients co-infected with HCV (positive serum viral load) and/or HIV (regardless of serum viral load).
- Patients participating at the time of inclusion in an interventional study
Show all 12Show fewer
- Persons under psychiatric care,
- Persons admitted to a health or social institution for purposes other than research
- Adults under legal protection (legal guardianship, tutorship, curatorship)
- Persons not affiliated to a social security scheme or beneficiaries of a similar scheme.
- Patients with abdominal skin lesions and/or infections.
- Contraindication to lidocaine administration (allergy or hypersensitivity to the product).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hepatology Department - Hospices Civils de Lyon
Lyon, 69004
Fabien ZOULIM, PU-PH, 04 26 10 93 55 ext. +33, fabien.zoulim@chu-lyon.fr
Fabien ZOULIM, PU-PH
About this study
Official title: Evaluation of the Intrahepatic Hepatitis B Virus Reservoir and Its Immunological Characteristics in Chronically HBV-infected Patients - Pilot Study
Two hundred and ninety-six million people worldwide are chronically infected with the hepatitis B virus (HBV), with around 750,000 deaths each year linked to the development of cirrhosis or hepatocellular carcinoma. Current treatments based on nucleoside analogues (NA) achieve virological cure in only 5% of cases at 10 years. The virological persistence of HBV is explained by the persistence of cccDNA (covalently-closed circular DNA) in the nucleus of hepatocytes. Complex and poorly understood interactions between immunological and virological responses explain the persistence of ccccDNA. A better understanding of the immunological and virological interactions of the intrahepatic compartment during chronic HBV infection is needed to better understand the mechanisms of viral persistence and for research and development of new drugs to achieve the goal of a functional cure for HBV (defined as the prolonged loss of Hepatitis B surface antigen (HBsAg) after cessation of treatment, associated with a decrease in intrahepatic cccDNA or its transcriptional inactivation).
The intra-hepatic compartment can be explored by liver biopsy. A fine needle aspiration (FNA) technique is used to characterize primary hepatic tumors, with fewer complications than liver biopsy. One study has validated its use for immunological exploration of the intra-hepatic compartment. Finally, a recently published study confirms a correlation between FNA and liver biopsy virological markers in patients with chronic HBV infection. However, no combined immuno-virological study has been carried out to explore this intra-hepatic compartment by FNA in patients with chronic HBV infection.
The investigators will assess the intrahepatic compartment of patients chronically infected with HBV (+/- hepatitis Delta (HDV)) to understand the mechanisms of viral persistence and characterize host immune responses to HBV. These investigations will make it possible to determine the immuno-virological profiles of patients who would benefit from intensification of antiviral treatment or, potentially, discontinuation of antiviral therapy.
- Conditions
- Chronic Hepatitis b
- Being tested
- Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Creation of a serum biobank, FNA feasibility and acceptability questionnaire
- Keywords
- Hepatitis B, HBV, cccDNA, functional cure, FNA, HBsAg
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) techniqueProcedure or surgery
The FNA will be performed at the Croix Rousse digestive pathology day hospital of the Hospices Civils de Lyon by a doctor from the hepatology department who has been trained to perform FNA.
After echography, a subcutaneous anesthesia with LIDOCAÏNE is administered. Two FNA passages will be performed for virological and immunological analyses. The patient will be monitored in the supine position for 1 hour after the procedure.
A single FNA will be performed during the study.
Creation of a serum biobankBiological
42ml blood sample for study of circulating peripheral blood mononuclear cells (PBMC) and new circulating hepatitis B markers. These samples will enable us to gain a better understanding of peripheral immune responses and to correlate intrahepatic virological data with new serum markers of HBV.
FNA feasibility and acceptability questionnaireOther
An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed.
| Study group | Role | What they receive |
|---|---|---|
| HBsAg <100 IU/ml | Experimental | Patients chronically mono-infected with HBV, whose HBsAg is less than 100 IU/ml (patients treated or not with NA) Receives: Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique; Biological: Creation of a serum biobank; Other: FNA feasibility and acceptability questionnaire |
| HBsAg between 100 and 3000 IU/ml | Experimental | Patients chronically mono-infected with HBV, with HBsAg levels >100 and <3000 IU/ml (patients treated or not with NA). Receives: Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique; Biological: Creation of a serum biobank; Other: FNA feasibility and acceptability questionnaire |
| HBsAg ≥ 3000 IU/ml | Experimental | Patients chronically mono-infected with HBV, with HBsAg levels ≥ 3000 IU/ml (patients treated or not with NA). Receives: Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique; Biological: Creation of a serum biobank; Other: FNA feasibility and acceptability questionnaire |
| Loss of HBsAg (spontaneously or under NA) | Experimental | Patients with loss of HBsAg (spontaneously or under NA). This group will allow comparison of the HBsAg loss immuno-virological profile with that of patients with active infection and varying levels of HBsAg (groups 1-3 and 5) and aid in identifying of predictors of functional cure. The identification of determinants of HBV functional cure is fundamental and is comparable to investigations that have been carried out in HIV-infected "elite controllers". Receives: Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique; Biological: Creation of a serum biobank; Other: FNA feasibility and acceptability questionnaire |
| Patients co-infected with HBV and HDV | Experimental | Patients co-infected with HDV (positive HDV viral load), regardless of HBsAg level (presence or absence of HBV or HDV treatment) Receives: Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique; Biological: Creation of a serum biobank; Other: FNA feasibility and acceptability questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interaction between immune response against HBV and intrahepatic HBV viral load
The main objective is to analyze the interaction between intrahepatic adaptive immune responses (Number and functional profile of CD4+ T lymphocytes and CD8+ B lymphocytes) and intrahepatic HBV viral load obtained from FNA.
Immune and virological responses obtained from the FNA performed.
Measured: Baseline
Secondary outcomes (4)
Correlation between intrahepatic HBV markers and HBV serum markers
Correlate intrahepatic markers of HBV (copies of intra-hepatic HBV, cccDNA, cccDNA transcriptional activity, HBV RNA) and new serum markers of HBV cure (circulating viral RNA, HBcrAg) and their evolution over time Intrahepatic HBV markers obtained from the FNA performed. New serum markers are taken at each visit for 24 months
Measured: Baseline, 6 months, 12 months, 18 months and 24 months after inclusion
Intrahepatic immune and virological responses in relation to the phases of HBV or HDV co-infection
Analyze immune (copies of intra-hepatic HBV, cccDNA and cccDNA transcriptional activity) and virological responses (Number and functional profile of CD4+ T lymphocytes and CD8+ B lymphocytes) as a function of the phases of chronic HBV infection and co-infection with HDV.
Immune and virological responses obtained from the FNA performed.
Measured: Baseline
Intrahepatic immunological and virological responses according to the presence or absence of NA
Analyze immune (copies of intra-hepatic HBV, cccDNA and cccDNA transcriptional activity) and virological responses (Number and functional profile of CD4+ T lymphocytes and CD8+ B lymphocytes) according to the presence or absence of NA treatment.
Immune and virological responses obtained from the FNA performed.
Measured: Baseline
Assessing patient tolerance and acceptability of FNA
A questionnaire on the acceptability and tolerance of FNA will be given to each patient at the inclusion visit and after FNA has been performed (15-30 days after inclusion).
An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after FNA had been performed.
Measured: Baseline (before then after FNA)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start8 Mar 2024
- Primary completion8 Mar 2030 (estimated)
- Study completion8 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis bStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Factorial
- Model description
- Five groups according to HBsAg quantification (3 distinct groups with or without nucleoside analogues), HDV co-infection and HBsAg loss.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fabien ZOULIM, PU-PH, Principal investigator, Service d'Hépatologie de l'Hopital Croix-Rousse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06047093
- Sponsor's protocol ID
- 69HCL23_0275
- Acronym
- RES-HBV
- Status last verified
- Apr 2026
- First submitted
- 14 Sep 2023
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Intrahepatic Hepatitis B Virus Reservoir and Its Immunological Characteristics in Chronically HBV-infected Patients - Pilot Study
- ClinicalTrials.gov ID
- NCT06047093
- Acronym / sponsor ID
- RES-HBV / 69HCL23_0275
- Conditions
- Chronic Hepatitis b
- Keywords
- Hepatitis B, HBV, cccDNA, functional cure, FNA, HBsAg
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 8 Mar 2024 (actual)
- Primary completion
- 8 Mar 2030 (estimated)
- Study completion
- 8 Mar 2030 (estimated)
- First posted
- 21 Sep 2023 (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.
Two hundred and ninety-six million people worldwide are chronically infected with the hepatitis B virus (HBV), with around 750,000 deaths each year linked to the development of cirrhosis or hepatocellular carcinoma. Current treatments based on nucleoside analogues (NA) achieve virological cure in only 5% of cases at 10 years. The virological persistence of HBV is explained by the persistence of cccDNA (covalently-closed circular DNA) in the nucleus of hepatocytes. Complex and poorly understood interactions between immunological and virological responses explain the persistence of ccccDNA. A better understanding of the immunological and virological interactions of the intrahepatic compartment during chronic HBV infection is needed to better understand the mechanisms of viral persistence and for research and development of new drugs to achieve the goal of a functional cure for HBV (defined as the prolonged loss of Hepatitis B surface antigen (HBsAg) after cessation of treatment, associated with a decrease in intrahepatic cccDNA or its transcriptional inactivation).
The intra-hepatic compartment can be explored by liver biopsy. A fine needle aspiration (FNA) technique is used to characterize primary hepatic tumors, with fewer complications than liver biopsy. One study has validated its use for immunological exploration of the intra-hepatic compartment. Finally, a recently published study confirms a correlation between FNA and liver biopsy virological markers in patients with chronic HBV infection. However, no combined immuno-virological study has been carried out to explore this intra-hepatic compartment by FNA in patients with chronic HBV infection.
The investigators will assess the intrahepatic compartment of patients chronically infected with HBV (+/- hepatitis Delta (HDV)) to understand the mechanisms of viral persistence and characterize host immune responses to HBV. These investigations will make it possible to determine the immuno-virological profiles of patients who would benefit from intensification of antiviral treatment or, potentially, discontinuation of antiviral therapy.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Five groups according to HBsAg quantification (3 distinct groups with or without nucleoside analogues), HDV co-infection and HBsAg loss.
| Arm | Type | Receives |
|---|---|---|
| HBsAg <100 IU/ml | Experimental | Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Biological: Creation of a serum biobank, Other: FNA feasibility and acceptability questionnairePatients chronically mono-infected with HBV, whose HBsAg is less than 100 IU/ml (patients treated or not with NA) |
| HBsAg between 100 and 3000 IU/ml | Experimental | Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Biological: Creation of a serum biobank, Other: FNA feasibility and acceptability questionnairePatients chronically mono-infected with HBV, with HBsAg levels >100 and <3000 IU/ml (patients treated or not with NA). |
| HBsAg ≥ 3000 IU/ml | Experimental | Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Biological: Creation of a serum biobank, Other: FNA feasibility and acceptability questionnairePatients chronically mono-infected with HBV, with HBsAg levels ≥ 3000 IU/ml (patients treated or not with NA). |
| Loss of HBsAg (spontaneously or under NA) | Experimental | Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Biological: Creation of a serum biobank, Other: FNA feasibility and acceptability questionnairePatients with loss of HBsAg (spontaneously or under NA). This group will allow comparison of the HBsAg loss immuno-virological profile with that of patients with active infection and varying levels of HBsAg (groups 1-3 and 5) and aid in identifying of predictors of functional cure. The identification of determinants of HBV functional cure is fundamental and is comparable to investigations that have been carried out in HIV-infected "elite controllers". |
| Patients co-infected with HBV and HDV | Experimental | Procedure: Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Biological: Creation of a serum biobank, Other: FNA feasibility and acceptability questionnairePatients co-infected with HDV (positive HDV viral load), regardless of HBsAg level (presence or absence of HBV or HDV treatment) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult patients (≥ 18 years of age)
- Patients chronically infected with hepatitis B virus at any stage of infection
- Nucleoside Analogues-treated or untreated
- Co-infected or not with HDV
- Included in the prospective CirB-RNA study (part of the CirB-RNA university research program) (ID-RCB : 2018-A02558-47, NCT03825458)
Key exclusion criteria (12 listed)
- Pregnant, parturient or breast-feeding women,
- Patients with decompensated cirrhosis
- Patients with hepatocellular carcinoma (suspected or proven),
- Liver transplant patients (even if liver transplantation for HBV),
- Patients co-infected with HCV (positive serum viral load) and/or HIV (regardless of serum viral load).
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 |
|---|---|---|
| Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) techniqueThe FNA will be performed at the Croix Rousse digestive pathology day hospital of the Hospices Civils de Lyon by a doctor from the hepatology department who has been trained to perform FNA. After echography, a subcutaneous anesthesia with LIDOCAÏNE is administered. Two FNA passages will be performed for virological and immunological analyses. The patient will be monitored in the supine position for 1 hour after the procedure. A single FNA will be performed during the study. | Procedure or surgery | HBsAg <100 IU/ml, HBsAg between 100 and 3000 IU/ml, HBsAg ≥ 3000 IU/ml, Loss of HBsAg (spontaneously or under NA), Patients co-infected with HBV and HDV |
| Creation of a serum biobank42ml blood sample for study of circulating peripheral blood mononuclear cells (PBMC) and new circulating hepatitis B markers. These samples will enable us to gain a better understanding of peripheral immune responses and to correlate intrahepatic virological data with new serum markers of HBV. | Biological | HBsAg <100 IU/ml, HBsAg between 100 and 3000 IU/ml, HBsAg ≥ 3000 IU/ml, Loss of HBsAg (spontaneously or under NA), Patients co-infected with HBV and HDV |
| FNA feasibility and acceptability questionnaireAn FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed. | Other | HBsAg <100 IU/ml, HBsAg between 100 and 3000 IU/ml, HBsAg ≥ 3000 IU/ml, Loss of HBsAg (spontaneously or under NA), Patients co-infected with HBV and HDV |
Primary outcome
Interaction between immune response against HBV and intrahepatic HBV viral load
Time frame: Baseline
The main objective is to analyze the interaction between intrahepatic adaptive immune responses (Number and functional profile of CD4+ T lymphocytes and CD8+ B lymphocytes) and intrahepatic HBV viral load obtained from FNA. Immune and virological responses obtained from the FNA performed.
4 secondary outcomes
Correlation between intrahepatic HBV markers and HBV serum markers
Time frame: Baseline, 6 months, 12 months, 18 months and 24 months after inclusion
Intrahepatic immune and virological responses in relation to the phases of HBV or HDV co-infection
Time frame: Baseline
Intrahepatic immunological and virological responses according to the presence or absence of NA
Time frame: Baseline
Assessing patient tolerance and acceptability of FNA
Time frame: Baseline (before then after FNA)
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 21 Apr 2026.
- Individual participant dataSharing planned: No
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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.
Fabien ZOULIM, PU-PH principal investigator
Service d'Hépatologie de l'Hopital Croix-Rousse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique, Creation of a serum biobank and FNA feasibility and acceptability questionnaire in people with Chronic Hepatitis b, run by Hospices Civils de Lyon at 1 site 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 6 inclusion and 12 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 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Fabien ZOULIM, PU-PH (0426109355 ext. +33, fabien.zoulim@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interaction between immune response against HBV and intrahepatic HBV viral load (time frame: Baseline). 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 21 Apr 2026.