Chronic Hepatitis B Infection
Conditions
Keywords
Hepatitis B, Chronic HBV infection, Hepatitis D, HBV, HDV, Liver fibrosis, Antiviral treatment
Brief summary
France is a low-endemicity country for hepatitis B virus (HBV) infection. In 2016, the prevalence of chronic HBV infection in the general population was estimated at 0.3%, corresponding to more than 135,000 HBsAg-positive individuals, of whom 82% were unaware of their infection. Data on hepatitis D virus (HDV) infection remain limited; however, available studies suggest a prevalence of 6% to 10% among HBsAg-positive individuals. Despite current guideline recommendations, up to 35% of newly diagnosed HBsAg-positive patients between 2018 and 2022 were not screened for HDV infection. The World Health Organization (WHO) targets for 2030 include a 90% reduction in the incidence of chronic viral hepatitis, a 65% reduction in hepatitis-related mortality, and treatment coverage for 80% of eligible diagnosed individuals. Achieving these goals will require strengthening HBV and HDV screening strategies and improving linkage to care and retention throughout the care cascade. Objectives: The primary objective is to assess the severity of liver disease, including significant fibrosis (≥F2) and cirrhosis (F4), among adults newly diagnosed with chronic HBV infection (with or without HDV infection) at Expert/Reference Hepatology Centers and Hepatology or Infectious Diseases Departments. The secondary objectives are to: 1. Describe demographic and virological characteristics of HBsAg-positive patients; 2. Determine the proportion of patients eligible for HBV treatment and evaluate treatment response at 6 and 12 months; 3. Assess the utility of novel virological markers for classifying patients according to phases of chronic HBV infection; 4. Evaluate HBsAg thresholds, in combination with other markers, for distinguishing HBeAg-negative chronic infection from HBeAg-negative chronic hepatitis; 5. Compare clinical and virological characteristics of HBV-monoinfected and HBV/HDV-coinfected patients; 6. Identify molecular signatures associated with liver disease severity; 7. Compare findings with those of a national cohort conducted 15 years earlier; 8. Collect biological samples for future analyses; 9. Assess the clinical utility of a highly sensitive HBcrAg assay. Method: This is a multicenter, observational study including all adults aged ≥18 years with chronic HBV infection, whether managed as outpatients or inpatients, who are newly referred to Expert/Reference Hepatology Centers or to Hepatology or Infectious Diseases Departments. Conclusions: This study will generate updated national data on liver disease severity, treatment eligibility, and virological characteristics among adults newly diagnosed with chronic HBV infection in France.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Chronic HBsAg carriage * First referral to participating expert/reference hepatology centers or hepatology/infectious diseases departments * Written informed consent obtained * Affiliation with national health insurance system or equivalent coverage
Exclusion criteria
* Telephone-only referrals or medical record-only consultations * Telemedicine-only consultations * Inability or unwillingness to comply with study procedures * Inability to understand study objectives or procedures * Individuals deprived of liberty, under guardianship or under conservatorship
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with significant fibrosis (METAVIR score ≥F2), including cirrhosis (METAVIR score F4) | Baseline (at inclusion) | Liver disease severity assessed by non-invasive methods (liver stiffness measurement, direct or indirect serum biomarkers, composite scores such as FIB-4) and/or liver biopsy. Significant fibrosis is defined as METAVIR score F2 or higher |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Demographic characteristics of newly identified chronic HBsAg carriers | Baseline (at inclusion) | age, sex, country of birth |
| Virological characteristics of newly identified chronic HBsAg carriers | Baseline (at inclusion) | HBe status, HBV DNA level, genotype, HBsAg level, HBcrAg level, HBV RNA level, HIV or HCV coinfections |
| Antiviral treatment eligibility and response | Baseline (at inclusion), 6 months and 12 months | ALT and AST levels, HBV DNA level, HBsAg level, HBe status and severity of liver disease |
| Performance of novel virological markers (HBcrAg level and HBV RNA level) in identifying patients at risk of disease progression | Baseline (at inclusion) | ALT and AST levels, HBV DNA level, HBsAg level, HBe status, severity of liver disease (METAVIR score), HBcrAg level and HBV RNA level |
| Diagnostic performance of HBsAg thresholds, in combination with other virological markers for distinguishing HBeAg-negative chronic HBV infection from HBeAg-negative chronic hepatitis B | Baseline (at inclusion) | HBsAg levels, HBe status and HBV DNA levels |
| Characteristics of HDV infection | Baseline (at inclusion) | ALT and AST levels, HBV DNA level, HBsAg and HBcrAg levels, HBe status, HBV genotype, severity of liver disease and proportion of patients treated with bulevirtide with or without pegylated interferon |
| Genome sequence analysis and identification of HBV motifs associated with the severity of liver disease in HBV/HDV-coinfected patients | Baseline (at inclusion) | Whole genome sequence analysis using next-generation sequencing technology |
| Comparison with previous French cohort data (2008-2012) | Baseline (at inclusion) | Evolution of clinical, biological and demographical characteristics of participants enrolled between 2008 and 2012 |
| Biobank collection | Baseline (at inclusion) | Collection and storage of whole blood samples |
| Clinical performance of ultra-sensitive HBcrAg assay (iTACT-HBcrAg) | Baseline (at inclusion) | sensitivity, specificity, positive and negative predictive values |
Countries
France
Contacts
CONTACTStéphane Chevaliez, PhD
CONTACTMeriem Harrabi, PhD
Outcome results
None listed