To characterize the phenotype, function and gene expression profiles of immune cells and hepatocytes in blood and liver of patients with viral hepatitis before, during and after treatment with antivirals.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the functionality of immune cells in the liver and blood in chronic
HCV and chronic HBV patients before, and during or after treatment with
antiviral treatment, as well as their gene expression profiles.
Secondary outcome
not applicable
Background summary
Viral hepatitis, caused by the hepatitis B virus (HBV) or the hepatitis C virus
(HCV), affects approximately 350 million people worldwide, resulting in a
significant disease burden worldwide. Chronic hepatitis B and C infection are
responsible for the majority of cases of fibrosis/cirrhosis and hepatocellular
carcinoma. The treatment for both chronic HBV and HCV has improved greatly. The
standard of care for chronic HBV patients eligible for treatment is currently
either entecavir or tenofovir (both nucleos(t)ide analogues), which are
tolerated extremely well, but have to be taken life-long. Also, the development
of direct acting antiviral drugs (DAA) to treat HCV is a major improvement, and
have entered clinical practice in the last 2 years. DAA have a favorable
tolerability profile, high barrier to resistance and a short treatment duration
using an all oral regimen4.
For both chronic HBV as for chronic HCV, there is limited information on
putative restoration of the impaired peripheral and intrahepatic immune system
during or after successful treatment with antivirals. This is important for the
evaluation of strategies to further improve therapy in patients with viral
breakthroughs for HCV, but also to better understand the processes of
regression of fibrosis as has been observed to occur upon elimination of HBV or
HCV. In addition, a better understanding of the immune status of chronic HBV
patients on therapy may provide important information that may help in
decision-making on the design and selection of novel antivirals that are in the
pipeline and that are aimed at complete eradication of HBV from infected
hepatocytes, instead of suppression of viral replication as is currently
achieved by tenofovir and entecavir. The aim of this study is to perform
longitudinal sampling of chronically infected patients who are being treated
for HBV or HCV to describe the intrahepatic effects on both the immunological
and transcriptomic level.
Study objective
To characterize the phenotype, function and gene expression profiles of immune
cells and hepatocytes in blood and liver of patients with viral hepatitis
before, during and after treatment with antivirals.
Study design
Investigator-initiated prospective single centre study
Intervention
Per time point max. 50 ml of peripheral blood and fine needle aspirate biopsies
will be collected.
Study burden and risks
Patients enrolled in this study will be treated for their chronic hepatitis C
or B and will not directly benefit from this study. Per patient 3 fine-needle
aspiration biopsies will be collected. This is a minimally invasive technique
to obtain safe and repeated liver samples. The procedure is well tolerated by
patients and has been performed for many years by our team without any
complications related to the procedure. Moreover, it can be performed on any
patient without anaesthesia or other preparations. Furthermore, 3 blood
collections will be performed for each patient. Blood collections do not pose
an extra risk for the patient.
's Gravendijkwal 230
Rotterdam 3015 CE
NL
's Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
* Diagnosed with chronic HCV or chronic HBV
* Hepatitis C viral RNA detectable in case of chronic HCV infection or HBsAg positive for over 6 months in case of chronic HBV infection.
* Non-cirrhotic compensated liver disease.
* Age * 18 years and * 70 years.
* Written informed consent.
Exclusion criteria
* Extensive bridging fibrosis indicated by histology (gold standard), imaging, transient elastography or 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.
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 | NL60125.078.16 |