Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Outcomes and Response to Bulevirtide Treatment (MPR_BD)

Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Association With Disease Outcomes and Response to Bulevirtide Treatment

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).

Study Overview

• Status: Recruiting
• Conditions: Hepatitis D
• Intervention / Treatment: Drug: Bulevirtide

• Study Type: Observational
• Enrollment (Estimated): 192

Contacts and Locations

• Study Contact: Name: Pietro Lampertico, MD; Phone Number: 0255035432; Email: pietro.lampertico@unimi.it

Study Locations

• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.
    • Contact: Pietro Lampertico, MD; Phone Number: 0255035432; Email: pietro.lampertico@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hepatis Delta naive; Patients with HDV infection naïve to Bulevirtide therapy
Hepatis Delta in therapy; Patients with HDV cirrhosis consecutively started on Bulevirtide therapy during the study enrollment period	Drug: Bulevirtide; dose of 2 mg/day subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Collaborators: University of Rome Tor Vergata; University of Milan; Parma University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Actual): November 30, 2025
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: July 5, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepatitis; Hepatitis D; bulevirtide
• Other Study ID Numbers: P2022WEXP2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No