Clinical trial NCT06047093: Fine Needle Aspiration (FNA) Evaluation of the Intrahepatic HBV Reservoir and Its Immunological Characteristics in Chronically HBV-infected Patients
Official title: Evaluation of the Intrahepatic Hepatitis B Virus Reservoir and Its Immunological Characteristics in Chronically HBV-infected Patients - Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Hepatitis b
Keywords: Hepatitis B
HBV
cccDNA
functional cure
FNA
HBsAg
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Five groups according to HBsAg quantification (3 distinct groups with or without nucleoside analogues), HDV co-infection and HBsAg loss.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Interaction between immune response against HBV and intrahepatic HBV viral load
timeFrame: Baseline
Secondary outcomes:
measure: Correlation between intrahepatic HBV markers and HBV serum markers
timeFrame: Baseline, 6 months, 12 months, 18 months and 24 months after inclusion
measure: Intrahepatic immune and virological responses in relation to the phases of HBV or HDV co-infection
timeFrame: Baseline
measure: Intrahepatic immunological and virological responses according to the presence or absence of NA
timeFrame: Baseline
measure: Assessing patient tolerance and acceptability of FNA
timeFrame: Baseline (before then after FNA)
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hepatology Department - Hospices Civils de Lyon
Study officials:
affiliation: Service d'Hépatologie de l'Hopital Croix-Rousse
name: Fabien ZOULIM, PU-PH
role: PRINCIPAL_INVESTIGATOR
References: