Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Outcomes and Response to Bulevirtide Treatment
NCT Number: NCT06504485
Acronym: MPR_BD
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Hepatitis D
Interventions: DRUG: Bulevirtide
Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Collaborators: University of Milan|Parma University Hospital|University of Rome Tor Vergata
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 192
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09-01
Completion Date: 2025-12-31
Locations: Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy., Milano, 20122, Italy

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).

Primary Outcome Measures: Calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide, 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|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), 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), Month 12
Secondary Outcome Measures: Correlate HDV-specific T cell response with stage of liver disease, Correlation of HDV-specific T cell response with stage of liver disease, through study completion, an average of 2 year|Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting the stage of liver disease, Quantification of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) and correlation with the stage of liver disease, through study completion, an average of 2 year|Correlate the quantification of HDV RNA within exosomes with the stage of liver disease, Correlation between the quantification of HDV RNA within exosomes and the disease phenotype, through study completion, an average of 2 year|Investigate the correlation between the genetic heritage of HDV and the stage of liver disease, Correlation between the genetic heritage of HDV and the stage of liver disease, through study completion, an average of 2 year|Define the transcriptional and molecular signatures of CD8 T cell dysfunction in patients with chronic HBV/HDV coinfection, Transcriptional and molecular signatures of CD8 T cell dysfunction in patients with chronic HBV/HDV coinfection, through study completion, an average of 2 year|Understanding the role of virus mutations in the virus's ability to escape CD8 T cell surveillance, Correlation between HDV mutations and the ability of the virus itself to escape CD8 T cell surveillance, through study completion, an average of 2 year|Correlate the prevalence of HDV-specific T cell responses with response to treatment over time, Correlation between the change in HDV-specific T responses, Month 6|Correlate the prevalence of HDV-specific T cell responses with response to treatment over time, Correlation between the change in HDV-specific T responses, Month 18|Correlate the prevalence of HDV-specific T cell responses with response to treatment over time, Correlation between the change in HDV-specific T responses, through study completion, an average of 2 year|Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting response to treatment with Bulevirtide;, Quantification of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) and correlation with response to treatment with Bulevirtide, through study completion, an average of 2 year|Correlate quantification of HDV RNA within exosomes with response to Bulevirtide treatment, Correlation between the quantification of HDV RNA within exosomes and the response to treatment with Bulevirtide, through study completion, an average of 2 year|Investigate the correlation between the genetic heritage of HDV and the response to treatment with Bulevirtide, Correlation between HDV genetic heritage and response to treatment with Bulevirtide, through study completion, an average of 2 year