Fine Needle Aspiration (FNA) Evaluation of the Intrahepatic HBV Reservoir and Its Immunological Characteristics in Chronically HBV-infected Patients

NCT ID: NCT06047093

Last Updated: 2024-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-08

Study Completion Date

2028-03-08

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Hepatitis b

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Five groups according to HBsAg quantification (3 distinct groups with or without nucleoside analogues), HDV co-infection and HBsAg loss.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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HBsAg <100 IU/ml

Patients chronically mono-infected with HBV, whose HBsAg is less than 100 IU/ml (patients treated or not with NA)

Group Type EXPERIMENTAL

Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique

Intervention Type PROCEDURE

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 biobank

Intervention Type BIOLOGICAL

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 questionnaire

Intervention Type OTHER

An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed.

HBsAg between 100 and 3000 IU/ml

Patients chronically mono-infected with HBV, with HBsAg levels \>100 and \<3000 IU/ml (patients treated or not with NA).

Group Type EXPERIMENTAL

Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique

Intervention Type PROCEDURE

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 biobank

Intervention Type BIOLOGICAL

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 questionnaire

Intervention Type OTHER

An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed.

HBsAg ≥ 3000 IU/ml

Patients chronically mono-infected with HBV, with HBsAg levels ≥ 3000 IU/ml (patients treated or not with NA).

Group Type EXPERIMENTAL

Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique

Intervention Type PROCEDURE

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 biobank

Intervention Type BIOLOGICAL

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 questionnaire

Intervention Type OTHER

An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed.

Loss of HBsAg (spontaneously or under NA)

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".

Group Type EXPERIMENTAL

Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique

Intervention Type PROCEDURE

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 biobank

Intervention Type BIOLOGICAL

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 questionnaire

Intervention Type OTHER

An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed.

Patients co-infected with HBV and HDV

Patients co-infected with HDV (positive HDV viral load), regardless of HBsAg level (presence or absence of HBV or HDV treatment)

Group Type EXPERIMENTAL

Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique

Intervention Type PROCEDURE

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 biobank

Intervention Type BIOLOGICAL

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 questionnaire

Intervention Type OTHER

An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed.

Interventions

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Investigation of the intrahepatic compartment using the fine needle aspiration (FNA) technique

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.

Intervention Type PROCEDURE

Creation of a serum biobank

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.

Intervention Type BIOLOGICAL

FNA feasibility and acceptability questionnaire

An FNA feasibility and acceptability questionnaire carried out at inclusion (V1) and after the FNA has been performed.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fabien ZOULIM, PU-PH

Role: PRINCIPAL_INVESTIGATOR

Service d'Hépatologie de l'Hopital Croix-Rousse

Locations

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Hepatology Department - Hospices Civils de Lyon

Lyon, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Fabien ZOULIM, PU-PH

Role: CONTACT

0426109355 ext. +33

Bénédicte POUMAROUX

Role: CONTACT

04 26 73 27 37 ext. +33

Facility Contacts

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Fabien ZOULIM, PU-PH

Role: primary

04 26 10 93 55 ext. +33

Other Identifiers

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69HCL23_0275

Identifier Type: -

Identifier Source: org_study_id

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