Changes in Bile Acids and Microbiota in Patients With Hepatitis D Treated With Bulvertide (Bio-Delta)

February 17, 2026 updated by: Ponziani Francesca Romana, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Changes in Bile Acid Profile and Gut Microbiota in Patients Undergoing Treatment With Bulevirtide for Hepatitis Delta Virus Infection

HDV is an RNA virus that infects only in the presence of HBV, affecting about 13% of HBsAg carriers. In Italy, prevalence ranges from 3.2% to 9.3%. It increases the risk of cirrhosis, fulminant hepatitis, and HCC, particularly in high-risk groups (HIV, HCV, drug users, dialysis patients). Until 2020, pegIFN was the only therapy; since 2022, bulevirtide (BLV) has been available, blocking viral entry into hepatocytes and reducing HDV RNA and liver stiffness, with efficacy in 45-48% of patients, though the optimal treatment duration remains uncertain. The gut microbiota and bile acids also play a role in fibrosis and cirrhosis progression: dysbiosis, typical in cirrhotic patients, alters bile acid metabolism and increases intrahepatic toxicity.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Francesca Romana Ponziani
Phone Number: +390630159336
Email: francescaromana.ponziani@policlinicogemelli.it

Study Locations

Italy
- - Roma, Italy, 00168
    - Recruiting
    - Fondazione Policlinico Universitaro A. Gemelli IRCSS UOC CEMAD
    - Contact:
      
      Francesca Romana Ponziani
      
      Phone Number: 3471227242
      
      Email: francescaromana.ponziani@policlinicogemelli.it
    - Contact:
      
      Elisabetta Creta
      
      Phone Number: +390630159336 +393480778584
      
      Email: elisabetta.creta@policlinicogemelli.it

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Probability Sample

Study Population

Patients with chronic hepatitis or compensated liver cirrhosis (Child-Pugh Score A) related to HBV-HDV, at the time of the first prescription of BLV 2 mg, will be enrolled.

Description

Inclusion Criteria:

Patients with chronic HDV-related hepatitis or compensated liver cirrhosis (Child-Pugh class A)
Positive HDV RNA within the 24 weeks prior to enrollment
Ongoing antiviral therapy for HBV at the time of enrollment
First prescription of Bulevirtide 2 mg issued within 30 days prior to enrollment
Caucasian ethnicity
Age ≥18 years
Normocaloric omnivorous diet
No intake of antibiotics, probiotics, or prebiotics in the month prior to enrollment
Signed informed consent

Exclusion Criteria:

Decompensated liver cirrhosis (Child-Pugh Score B or C)
Patients without HBV-HDV-related infection/hepatitis/cirrhosis
Age ≤18 years
Pregnant or breastfeeding women
Concomitant diseases with short life expectancy (solid or hematologic neoplasms, heart failure NYHA III/IV, COPD GOLD C-D)
Conditions (celiac disease, chronic inflammatory bowel diseases) or use of medications (antibiotics, probiotics, prebiotics) capable of altering gut microbiota composition

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut Microbiota in HBV-HDV Patients on Bulevirtide Time Frame: 2-18 months	To describe the composition of the intestinal microbiota (IM)of patients with chronic hepatitis/compensated HBV-HDV cirrhosis receiving BLV 2 mg/day at enrollment and at weeks 12, 24, and 48.	2-18 months
Bile Acids in HBV-HDV Patients on Bulevirtide Time Frame: 2-18 months	To describe the composition of the fecal bile acids (BA) of patients with chronic hepatitis/compensated HBV-HDV cirrhosis receiving BLV 2 mg/day at enrollment and at weeks 12, 24, and 48.	2-18 months
Inflammation in HBV-HDV Patients on Bulevirtide Time Frame: 2-18 months	To describe the systemic inflammatory of patients with chronic hepatitis/compensated HBV-HDV cirrhosis receiving BLV 2 mg/day at enrollment and at weeks 12, 24, and 48.	2-18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Characteristics and Treatment Response in HBV-HDV Cirrhosis Time Frame: 2-18 months	assess characteristics common to patients with chronic hepatitis or compensated liver cirrhosis HBV-HDV related to the first prescription of BLV 2 mg by examining their clinical and demographic history	2-18 months
Correlation of Microbiota and Bile Acids with HBV-HDV Treatment Response Time Frame: 2-24 months	To assess whether the composition of the intestinal microbiota (IM) and fecal bile acids (BA) is correlated with treatment efficacy at weeks 24, 48, and 96.	2-24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

Principal Investigator: Francesca Romana Ponziani, Fondazione Policlinico A. Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2025

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

September 12, 2025

First Submitted That Met QC Criteria

February 17, 2026

First Posted (Actual)

February 24, 2026

Study Record Updates

Last Update Posted (Actual)