HDV-Europe: Prevalence and Outcome of HDV in HIV/HBV Coinfection

Hepatitis D Clinical Trial

Official title:

Euro-HDV:Epidemiology and Clinical Course in Patients With HIV and Hepatitis B/D -Coinfection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06264583
• Other study ID #: IN-DE-980-6998
• Status: Recruiting
• Start date: May 1, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Bonn
• Contact: Jürgen Rockstroh
• Phone: +491716575969
• Email: juergen.rockstroh[@]ukbonn.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this project is to set up a cross-sectional cohort study (France, Germany, The Netherlands, Poland, Spain, Switzerland, Italy, United Kingdom and Portugal) to assess the implementation of EACS guidelines for HDV-testing among PLWH with positive HbsAg and thereby evaluate the prevalence of HDV infection among HIV/HBV-coinfected in 2023, as well as corresponding risk factors. In addition to the testing itself, this study will also set up a cohort and databasee for future HDV studies among PLWH, including clinical, virological und laboratory parameters.

1. Analyze the rate of HDV-testing and evaluate the prevalence of HDV-infection by testing.

1. Evaluation of former screening of HDV by assessing existing data at study sites.

2. Determination of the HDV prevalence in European PLWH and HBV coinfection.

2. Setting up a database of all PLWH with HBV/HDV coinfection

1. Analysis of transmission risk factors for HDV coinfection

2. Asses the rate of HDV positive patients with ongoing HDV replication.

3. Define the liver disease state by APRI score, fibroscan, ultrasound and routine laboratory test results.

Description:

Background Hepatitis D is caused by a defective RNA-virus, that is known to be among the smallest human pathogenic viruses. As it partly shares the viral entry into hepatocytes with HBV, a coinfection is mandatory (1). Besides a simultaneous infection with HBV and HDV, it might also occur in the sense of a superinfection to a preexisting HBV-infection (2). Though most of the acute infections recover spontaneously, a progression to chronic disease is well described (3). The persistence of HDV leads to an accelerated fibrosis progression and eventually to cirrhosis and an increased risk of developing hepatocellular carcinoma (HCC) as well (4, 5). With the widely established feasibility of immunization against viral Hepatitis B, numbers of HDV-infection in high-income countries are quite low. Nevertheless, the burden of chronic HDV-infection worldwide is high, as different studies estimate the number of patients from 12 million to up to 72 million (6-8).

In the subgroup of people living with HIV (PLWH), who are at increased risk for acquiring viral hepatitis in general, rates of HDV infection have been reported between 10%-20% of HIV/HBV-coinfected people, with variations according to region as well as transmission group. Particularly, early in the HV epidemic higher rates of HDV have been reported for HIV/HBV coinfected drug users. More recently, a shift from people who acquired HIV through drug injection (PWID) to men who have sex with men (MSM) has been reported with HDV coinfection rates of around 8% (9). Common for all PLWH with HBV/HDV-coinfection is a more rapid progression in liver disease (10), resulting in increased rates of decompensated cirrhosis and higher mortality (11, 12). Therefore, mandatory screening for HDV was implemented into current EACS guideline recommendations. However, there is still a lack of testing in daily routine, even at sites where testing is easily accessible and reimbursed. Moreover, most PLWH who are coinfected with HBV are tested at initial HBV diagnosis, but after being put on antiretroviral treatment, which usually includes a tenofovir-based therapy a follow-up testing of HDV does not take place routinely.

Objective The aim of this project is to set up a cross-sectional cohort study (France, Germany, The Netherlands, Poland, Spain, Switzerland, Italy, United Kingdom and Portugal) to assess the implementation of EACS guidelines for HDV-testing among PLWH with positive HbsAg and thereby evaluate the prevalence of HDV infection among HIV/HBV-coinfected in 2023, as well as corresponding risk factors. In addition to the testing itself, this study will also set up a cohort and databasee for future HDV studies among PLWH, including clinical, virological und laboratory parameters.

1. Analyze the rate of HDV-testing and evaluate the prevalence of HDV-infection by testing.

1. Evaluation of former screening of HDV by assessing existing data at study sites.

2. Determination of the HDV prevalence in European PLWH and HBV coinfection.

2. Setting up a database of all PLWH with HBV/HDV coinfection

1. Analysis of transmission risk factors for HDV coinfection

2. Asses the rate of HDV positive patients with ongoing HDV replication.

3. Define the liver disease state by APRI score, fibroscan, ultrasound and routine laboratory test results.

Cohort Design and Methods General In this multi-center cohort study patients with documented HIV/HBV-coinfection (2 measurements of positive HBsAg > 6month interval and Anti-HBc-positive) will be evaluated for past HDV screening (last 24 months).

Eligible participants must be 18 years of age or older.

Methods:

• HDV-replication will be measured by commercially used PCR-testing kits. The proportion of HDV serological positive individuals with ongoing viral replication will be determined. This will be collected for all patients with positive HDV serology.

• The liver disease stage, which is expressed by the fibrosis stage, will be determined by APRI score. Furthermore, other non-invasive imaging techniques, including standard ultrasound as well as Fibroscan will be used where available to evaluate the degree of liver disease. In addition, standard laboratory parameters (see, eCRF codebook, annex xyz), which are part of the routine testing among PLWH control visits, will be documented. Changes over time will be evaluated and put in relation to medical imaging, as far as available.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8000
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented HIV-infection confirmed by HIV-ELISA

• Chronic HBV Infection confirmed by d HBV HBsAg-testing (2 measurements of positive HBsAg > 6month interval).

Exclusion Criteria:

• PLWH with a cleared HBV-infection (anti-HBc or anti-HBc and anti-HBs antibody positive will be considered as HIV-monoinfected persons.

• Individuals younger than 18 years of age

• Patients with any social condition or living circumstances which may interfere with the conduct of the study, as anticipated by the investigator, such as incapacity to adequately understand the study content or not willing to cooperate will be excluded from the study. -For France, patients without adequate social security will be excluded.

Related Conditions & MeSH terms

• Coinfection
• Hepatitis
• Hepatitis A
• Hepatitis D

Intervention

Other:
• HDV screening
1. Analyze the rate of HDV-testing and evaluate the prevalence of HDV-infection by testing.

Locations

Country	Name	City	State
Germany	University Hospital Bonn	Bonn	NRW

Sponsors (17)

Lead Sponsor

Collaborator

University Hospital, Bonn

Amsterdam UMC, GEPCOI (Portuguese Group of Coinfection), Goethe University, Heinrich-Heine University, Duesseldorf, Henri Mondor University Hospital, Hospital General Universitario Gregorio Marañon, Hospital Universitario Infanta Leonor, ICH Hamburg, ICONA Cohort, King's College London, Praxiszentrum Hohenstaufenring Köln, Royal Free Hospital NHS Foundation Trust, Sorbonne University, Swiss HIV Cohort Study, University Hospital of Cologne, University Hospital, Essen

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Botelho-Souza LF, Vasconcelos MPA, Dos Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017 Sep 13;14(1):177. doi: 10.1186/s12985-017-0845-y. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HDV prevalence in HIV/HBV coinfection	percentage of HDV seropositive individuls with HIV/HBV coinfection	all data collected in 2023
Secondary	Degree of liver disease in pateints with HIV/HBV/HDV triple infection	assess liver fibrosis stage	all data collected in 2023