The focus of the research is a cross-sectional comparison between the samples of fine needle liver aspirates of patients at different chronic HBV infection phases with the aim to identify correlates between intrahepatic immune changes at the…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Per visit max.175 ml of peripheral blood and fine needle aspirate biopsies
(FNAB) will be collected. Multiple assessments are scheduled for the same time
point: vital signs, physical examination, blood collection for safety,
biochemical and serological parameters, blood collection for PBMC isolation,
blood collection for serum and whole blood parameters and liver FNABs. Cells
from blood and liver will be evaluated for their phenotype by flow cytometry,
and for their gene expression by RNA sequencing.
Secondary outcome
not applicable
Background summary
Globally 360 million people are chronically infected with hepatitis B virus
(HBV). In these patients the immune system is incapable of clearing the virus.
The levels of HBV DNA, ALT and hepatitis B envelope antigen (HBeAg) vary
greatly between patients, and may fluctuate in the same patient. The long-term
consequences of chronic HBV infection can be severe, since patients are at
increased risk for developing liver fibrosis, cirrhosis and/or hepatocellular
carcinoma. To better describe the disease state of the patient and to guide
treatment strategies, a clinical distinction into four phases was made based on
variations in serum HBV DNA, ALT and HBeAg levels. These four clinical HBV
phases are known as the immune tolerant (IT), immune active (IA), inactive
carrier (IC) and HBeAg-negative hepatitis (ENEG) phase. The molecular events
characterizing each phase and determining the transition between clinical
phases are still poorly understood.
The goal of this study is to understand the mechanism of immune control in
chronic HBV infection through detailed analysis of intrahepatic and peripheral
immune cell populations comparing the settings of immune control in the
different phases. Comparisons will be made between IT and IC, both of which
have minimal or no hepatic inflammation but very different levels of HBV
replication. Also comparison with IA and ENEG patients will be done,
recognizing that inflammation may confound results.
Study objective
The focus of the research is a cross-sectional comparison between the samples
of fine needle liver aspirates of patients at different chronic HBV infection
phases with the aim to identify correlates between intrahepatic immune changes
at the cellular or molecular level and viral control.
Study design
Cross-sectional, prospective multi-center study in about 125 CHB patients at 3
sites (Erasmus MC Rotterdam, University Hospital Toronto and Massachusetts
General Hospital).
Study burden and risks
Patients enrolled in this study will not directly benefit from this study as
this is an exploratory study to identify correlates between intrahepatic immune
changes at the cellular or molecular level and viral control.
Per patient 1 or 2 FNABs 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, blood
collections will be performed for each patient at each visit. Three is the
maximal number of blood collections in this study and blood collection does not
pose an extra risk for the patient.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
- man or woman, age of ><=18 and <<= 70 years
- chronic Hepatitis B (HBsAg positive for minimum 6 months)
- no evidence of cirrhosis
- HBV Genotype A, B, C, D or E
- otherwise healthy and medically stable
- written informed consent
- not on treatment for CHB
- disease stage specific ALT, HBeAg and HBV DNA (according to protocol)
Exclusion criteria
- positive HIV test
- hepatitis A, C, D or E co-infection
- decompensated cirrhosis or hepatocellular carcinoma (documented medical
history)
- participation in another translational research study or clinical study
- use of any investigational drug or use of an invasive investigational medical
device within 90 days before screening
- any condition for which, in the opinion of the investigator, participation
would not be in the best interest of the subject
- major surgery (e.g. requiring general anaesthesia) within 12 weeks before
screening
- history of drug or alcohol abuse within 1 year before 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 | NL61959.078.17 |