Hepatitis D
Conditions
Brief summary
Pharmacological, single-center, non-profit observational study. The present study is part of a cooperation project between the SC Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy), the University of Milan, the University of Parma and Rome Tor Vergata, funded under the call for Research Projects of Significant National Interest - 2022 PNRR Call (Prot. P2022WEXP2). Hepatitis D virus (HDV) is a defective RNA virus, which requires the presence of hepatitis B virus (HBV) to infect liver cells and propagate. To date, the mechanisms underlying the accelerated disease progression in the natural history of Delta hepatitis are poorly understood, as is the course of the HDV-specific immune response (CD4 and CD8 T cells). As in chronic HBV and HCV infections, the outcome of chronic HDV infection appears to be dictated primarily by the host immune response, which represents a key determinant for virus control or persistence. For HBV/HDV coinfection, the role of T cells has not been well defined, as suitable animal models are lacking and so far few HDV-specific T cell epitopes have been precisely mapped, mainly limited to HLA-B alleles. The study is divided into two substudies (cross-sectional and longitudinal). The primary objective of the cross-sectional study is to calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide. The primary objective of the longitudinal study is the change in the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection during treatment with Bulevirtide compared to baseline (pre-treatment).
Interventions
DRUGBulevirtide
dose of 2 mg/day subcutaneously
Sponsors
University of Milan
Parma University Hospital
University of Rome Tor Vergata
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Ability to understand and sign the informed consent * Chronic HDV infection defined by positivity of HBsAg antigen (HBV) and HDV RNA (HBV-HDV co-infection) for at least 6 months at the time of enrollment.
Exclusion criteria
* Co-infection with other viruses (HCV, HIV) * Treatment with immunosuppressive/immunomodulatory drugs * Other congenital and/or acquired immunodeficiency conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide | through study completion, an average of 2 year | Prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide |
| Change in the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection during treatment with Bulevirtide compared to baseline (pre-treatment) | Month 12 | Prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection after 12 months of treatment with Bulevirtide compared to baseline (pre-therapy) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlate the quantification of HDV RNA within exosomes with the stage of liver disease | through study completion, an average of 2 year | Correlation between the quantification of HDV RNA within exosomes and the disease phenotype |
| Investigate the correlation between the genetic heritage of HDV and the stage of liver disease | through study completion, an average of 2 year | Correlation between the genetic heritage of HDV and the stage of liver disease |
| Define the transcriptional and molecular signatures of CD8 T cell dysfunction in patients with chronic HBV/HDV coinfection | through study completion, an average of 2 year | Transcriptional and molecular signatures of CD8 T cell dysfunction in patients with chronic HBV/HDV coinfection |
| Understanding the role of virus mutations in the virus's ability to escape CD8 T cell surveillance | through study completion, an average of 2 year | Correlation between HDV mutations and the ability of the virus itself to escape CD8 T cell surveillance |
| Correlate HDV-specific T cell response with stage of liver disease | through study completion, an average of 2 year | Correlation of HDV-specific T cell response with stage of liver disease |
| Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting response to treatment with Bulevirtide; | through study completion, an average of 2 year | Quantification of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) and correlation with response to treatment with Bulevirtide |
| Correlate quantification of HDV RNA within exosomes with response to Bulevirtide treatment | through study completion, an average of 2 year | Correlation between the quantification of HDV RNA within exosomes and the response to treatment with Bulevirtide |
| Investigate the correlation between the genetic heritage of HDV and the response to treatment with Bulevirtide | through study completion, an average of 2 year | Correlation between HDV genetic heritage and response to treatment with Bulevirtide |
| Correlate the prevalence of HDV-specific T cell responses with response to treatment over time | Month 6 | Correlation between the change in HDV-specific T responses |
| Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting the stage of liver disease | through study completion, an average of 2 year | Quantification of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) and correlation with the stage of liver disease |
Countries
Italy
Contacts
Primary ContactPietro Lampertico, MD
Outcome results
None listed