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

Официальное название

Evaluation of the Intrahepatic Hepatitis B Virus Reservoir and Its Immunological Characteristics in Chronically HBV-infected Patients - Pilot Study

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Interaction between immune response against HBV and intrahepatic HBV viral load [Срок оценки: Baseline]

Вторичные конечные точки (4)

• Correlation between intrahepatic HBV markers and HBV serum markers [Срок оценки: 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 [Срок оценки: Baseline]
• Intrahepatic immunological and virological responses according to the presence or absence of NA [Срок оценки: Baseline]
• Assessing patient tolerance and acceptability of FNA [Срок оценки: Baseline (before then after FNA)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Факторный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Франция · 1 центр

• Hepatology Department - Hospices Civils de Lyon — Lyon

Идентификаторы

NCT: NCT06047093 · 69HCL23_0275

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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