An observational study in Hepatitis D, sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-15.
Sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Observational
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).
The study will enroll patients co-infected with HBV-HDV (defined by positivity of HDV RNA for at least 6 months) who meet the inclusion criteria and no exclusion criteria
Exclusion Criteria:
Patients with HDV infection naïve to Bulevirtide therapy
Patients with HDV cirrhosis consecutively started on Bulevirtide therapy during the study enrollment period
Drug: Bulevirtide
dose of 2 mg/day subcutaneously
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
Time frame: 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)
Time frame: Month 12
Correlate HDV-specific T cell response with stage of liver disease
Correlation of HDV-specific T cell response with stage of liver disease
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: through study completion, an average of 2 year
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Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico