To characterize the phenotype, function and gene expression profiles of immune cells and hepatocytes in blood and liver of patients with chronic hepatitis D.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The immuno-phenotype of CD4+ T cells, CD8+ T cells, monocytes/macrophages,
neutrophils, NK cells, NKT cells, MAIT cells, and B cells will be assessed in
blood and liver of patients chronic HBV-HDV.
The function of CD4+ T cells, CD8+ T cells, monocytes/macrophages, neutrophils,
NK cells, NKT cells, MAIT cells, and B cells will be assessed in blood.
Gene expression profiles of immune cells and hepatocytes in blood and liver of
patients will be assessed.
Secondary outcome
not applicable
Background summary
Hepatitis delta virus (HDV) is a defective RNA virus that requires presence of
hepatitis B virus (HBV) to complete virion assembly and secretion. HDV
infection can occur as an acute co-infection with HBV and HDV, which evolves to
chronicity in only 2% of patients, or as an HDV superinfection in patients with
a chronic HBV infection resulting in a chronic HBV-HDV co-infection in 70-90%
of patients. HBV-HDV coinfection (*hepatitis delta*) has been associated with
severe liver injury that may result in rapid progression to cirrhosis and
hepatic decompensation, as well as a higher risk of liver cancer when compared
to patients with HBV mono-infection. In a recent long-term follow-up study, 30%
of hepatitis delta patients had cirrhosis at the time of diagnosis, and 31% of
non-cirrhotic patients developed cirrhosis during a median follow-up of 8
years. These rates are similar to those reported in a cohort from the 1990*s.
At this time, therapeutic options for hepatitis delta are limited.
Peginterferon alfa (PEG-IFN) treatment may result in HDV RNA undetectability in
a small subset of patients, but relapse rates are high. Treatment with
nucleo(s)tide analogues (NUCs) does not directly influence HDV RNA levels, but
is effective in suppressing HBV replication and is therefore recommended in
patients with advanced liver disease and detectable HBV DNA.
There is limited information of the immune status of chronic HBV-HDV patients
off and on therapy which may provide important information that may help in
decision-making on the design and selection of novel antivirals that are in the
pipeline. The aim of this study is to perform longitudinal sampling of
chronically infected HBV-HDV patients to describe the immunological and
transcriptomic intrahepatic processes.
Sampling of the liver for research purposes is possible by the collection of
Fine Needle Aspirates (FNA). Complications like hemorrhage limit the frequent
performance of diagnostic core-needle biopsies (TB), and the cells of
peripheral blood have to be used as surrogate markers instead. The collection
of fine-needle-aspirates of the liver represents a safe and minimally traumatic
method that allows frequent cytological sampling. During this procedure a small
needle (25 Gauge or 0.5 mm) is used to aspirate hepatocytes and intrahepatic
leukocytes from the liver. The low rate of complications associated with a FNA
and the absence of anesthetic measures or observation nominates this method for
the follow up of liver immunology in a research setting.
Study objective
To characterize the phenotype, function and gene expression profiles of immune
cells and hepatocytes in blood and liver of patients with chronic hepatitis D.
Study design
prospective observational single center study
Study burden and risks
The current study does not pose any significant risk to the patients, and the
only burden is collection of blood and fine-needle aspirates. Both the blood
collection and FNA can cause pain and bruising. In rare cases, FNA can cause a
bleeding in the liver. The study has no direct benefit for the included
subjects.
Doctor Molewaterplein 40
Rotterdam 3015GD
NL
Doctor Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
- Active hepatitis delta based on a positive anti-HDV and a positive HDV-RNA
test
- Patients must be >=18 years and <= 70 years.
- Non-cirrhotic or cirrhotic compensated liver disease
- Patients must be able to provie a written informed consent
Exclusion criteria
• Clinical decompensated cirrhosis (Child-Pugh Grade B or C).
• Hepatic imaging (ultrasound, CT or MRI) with evidence of hepatocellular
carcinoma.
• Females who are pregnant or breast-feeding.
• History or other evidence of severe illness, malignancy or any other
condition which would make the patient, in the opinion of the investigators,
unsuitable for the study.
• Received prolonged therapy with immunomodulatory agents (e.g.
corticosteroids) or biologics (e.g. monoclonal antibody, interferon) within 6
months of screening.
• Thrombocytes < 60x109/L
• Inability to provide written informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85638.078.23 |