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

NCT06047093 | Recruiting

• 1 other identifier: 69HCL23_0275
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

Hepatitis B; HBV; cccDNA; functional cure; FNA; HBsAg

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline

Secondary Outcomes (4)

• Correlation between intrahepatic HBV markers and HBV serum markers

  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

  Baseline

• Intrahepatic immunological and virological responses according to the presence or absence of NA

  Baseline

• Assessing patient tolerance and acceptability of FNA

  Baseline (before then after FNA)

Study Arms (5)

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)

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).

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).

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".

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)

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

Interventions

Creation of a serum biobank 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.

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

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

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 questionnaire OTHER

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hepatology Department - Hospices Civils de Lyon

Lyon, 69004, France

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

Methods

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Fabien ZOULIM, PU-PH

  Service d'Hépatologie de l'Hopital Croix-Rousse

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabien ZOULIM, PU-PH

CONTACT

0426109355; fabien.zoulim@chu-lyon.fr

Bénédicte POUMAROUX

CONTACT

04 26 73 27 37; benedicte.poumaroux@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Five groups according to HBsAg quantification (3 distinct groups with or without nucleoside analogues), HDV co-infection and HBsAg loss.

Study Record Dates

• First Submitted: September 14, 2023
• First Posted: September 21, 2023
• Study Start: March 8, 2024
• Primary Completion (Estimated): March 8, 2030
• Study Completion (Estimated): March 8, 2030
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)