New HBV Infection Biomarkers: Clinical Characterization and Impact on Management

Recruiting

• Conditions: Chronic Hepatitis B Virus (HBV) Infection
• Interventions: Biological: Collection of blood samples for the study of HBV biomarkers

• Registration Number: NCT06906016
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Chronic Hepatitis B Virus (HBV) infection affects nearly 300 million people worldwide and is a leading cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In France, it affects around 0.3% of the population. Current clinical practice relies on traditional biomarkers, such as HBV DNA and HBsAg, to monitor viral replication and disease progression. However, these biomarkers do not fully capture the viral activity or predict clinical outcomes. Recently, new biomarkers like HBcrAg and HBV RNA have emerged, showing promise for better understanding the natural history of the infection and guiding treatment decisions. The main objective of this research is to evaluate the predictive role of these biomarkers (HBcrAg, HBV RNA) in HBV-infected patients, focusing on their association with HBsAg seroconversion and their ability to predict clinical events like cirrhosis and HCC. Secondary objectives include describing the clinicobiological characteristics of patients, determining HBV genotypes, characterizing the impact of HBV on the host's transcriptome, and studying the biomarkers' role in different phases of the infection and treatment. The ultimate goal is to identify more accurate biomarkers to guide antiviral treatment, predict disease progression, and potentially determine when treatment can be safely discontinued.

Detailed Description

This study focuses on the chronic Hepatitis B virus (HBV) infection, which affects nearly 300 million people globally, leading to cirrhosis, hepatocellular carcinoma (HCC), and other severe liver diseases. The objective is to evaluate new biomarkers for HBV infection, specifically HBV core-related antigen (HBcrAg) and HBV RNA, and their potential role in the clinical management and prognosis of the disease. Traditional biomarkers used to track viral replication and liver fibrosis, such as HBV DNA, HBeAg, and HBsAg, have limitations, which this study aims to address by exploring emerging biomarkers that could improve the understanding of the infection's natural history and response to antiviral treatments.

The population involved in the study includes patients diagnosed with chronic HBV infection and receiving care at Henri Mondor-Albert Chenevier University Hospital. Patients must be 18 years or older and have been infected with HBV (positive HBsAg for more than six months). Exclusion criteria include individuals with liver transplantation history, those unable to provide consent, pregnant or breastfeeding women, and those not affiliated with a Social Security scheme.

The study design includes both primary and secondary evaluation criteria. The primary criterion is the incidence of HBsAg seroconversion (absence of detectable HBsAg in serum). Secondary criteria include the proportion of patients positive for HBeAg, the incidence of clinical events like cirrhosis and HCC, and the molecular characterization of HBV, such as genotype distribution and the presence of co-infections like hepatitis C (HCV) or HIV. Other secondary criteria also include the measurement of liver fibrosis using Fibroscan and screening for HCC through abdominal ultrasound and alpha-fetoprotein (AFP) tests.

Research procedures involve routine medical consultations, with additional blood samples (9mL dry tube and 9mL Paxgene) collected for research purposes once a year. Patients will be followed for a period of 10 years, with regular monitoring of HBV biomarkers and liver status to evaluate the progression of the infection, the risk of developing liver disease, and the potential predictive value of new biomarkers for viral replication and clinical outcomes. The ultimate aim is to enhance HBV management by identifying predictive biomarkers and refining treatment strategies, particularly to optimize antiviral therapies and improve patient prognosis.

Study Timeline

• Study Start: 2023-11-28
• Status Verified: 2025-03
• Study First Submitted: 2025-03-04
• Study First Submitted QC: 2025-03-25
• Last Update Submitted: 2025-03-25
• Study First Posted: 2025-04-02
• Last Update Posted: 2025-04-02
• Primary Completion: 2038-11-27
• Study Completion: 2038-11-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

• 18 years old
• Chronic HBV infection (HbsAg positive carrier for more than 6 months)
• Patient under care within the Henri Mondor-Albert Chenevier University Hospital group

Exclusion Criteria

• History of liver transplantation for liver failure in the context of chronic HBV infection
• Protected adults, adults unable to express their consent
• Pregnant or breastfeeding women
• Person not affiliated with a Social Security system
• Patient refusal to participate in the project

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort Study on Chronic HBV Infection	Collection of blood samples for the study of HBV biomarkers	This study is a cohort study. It follows a group of patients infected with HBV (Hepatitis B) over an extended period to evaluate the predictive role of biomarkers in the progression of the infection and the response to antiviral treatment. Patients are monitored over time, with regular sample collection to measure biomarkers and assess clinical and biological events, such as seroconversion or the emergence of complications like cirrhosis or liver cancer.

Primary Outcome Measures

Name	Time	Method
HBsAg Seroconversion Rate	3 months	Defined by the absence of detectable AgHBs in the serum using ELISA test

Secondary Outcome Measures

Name	Time	Method
Incidence of Biological Events	1 year	Monitoring the seroconversion of HBeAg using biological data, measured by the proportion of patients with HBeAg seroconversion.
Quantification of VHB Transcripts	1 year	Quantitative analysis of VHB transcripts using PCR, measured in copies per milliliter (copies/ml).
Biomarker Quantification: VHB RNA	1 year	Quantification of the virus biomarker VHB RNA during follow-up using PCR, measured in copies per milliliter (copies/ml).
Diagnosis of Liver Tumor	1 year	Diagnostic assessment of liver tumors using medical imaging techniques, such as MRI
Incidence of Clinical Events	1 year	Monitoring of clinical events, such as cirrhosis, measured by the proportion of patients affected by clinical events.

Trial Locations

Locations (1)

Clinical Research Unit (CRU) Henri Mondor.; 🇫🇷 Creteil, Créteil, France