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

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).