To characterize the immune response and gene expression profiles in blood of chronic HBV patients who present with a flare after treatment with antiviral therapy in order to be able to predict spontaneous resolution of flares in the future.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Determine the percentages of (NK cells, B cells, T cells, monocytes and MAIT
cells) of the total lymphocyte population and the expression levels of the
relevant activation and inhibitory markers as well as assessing their function
and gene expression profile.
Secondary outcome
Not applicable.
Background summary
Long-term antiviral treatment for chronic hepatitis B with entecavir or
tenofovir is effective but also associated with mounting costs and potential
side effects. Discontinuation of treatment in patients who have undergone
long-term viral suppression appears to be safe and has been associated with
sustained response rates of 30 - 50% in several small series of patients
treated with older agents. The spectrum of outcomes after nucleos(t)ide
analogue cessation, ranging from functional cure to severe liver inflammation,
links intimately to the immune system. Relapse occurs frequently off treatment
and may lead to clinically significant flares. This risk should be as low as
possible, and preferably also predictable and thus preventable. In other words,
the ability to identify which patients should not stop or being able to predict
an imminent relapse to re-initiate retreatment is of utmost importance.
Immunologic biomarkers that discriminate between antiviral responses and
pathologic inflammation after stopping therapy could facilitate clinical
decisions, limit adverse outcomes, and identify mechanisms leading to
functional cure. However, specific mechanisms driving viral control and
inflammation in the human liver have not been completely defined. Evaluating
these mechanisms of intrahepatic immune responses in chronic hepatitis B
patients experiencing a flare after stopping nucleot(s)ide analogue therapy
requires longitudinal investigation of blood samples. This study will aim to
characterize immune and virological parameters and gene expression profiles in
blood of chronic HBV patients who present with a flare after stopping antiviral
treatment in order to be able to predict spontaneous resolution of flares.
Study objective
To characterize the immune response and gene expression profiles in blood of
chronic HBV patients who present with a flare after treatment with antiviral
therapy in order to be able to predict spontaneous resolution of flares in the
future.
Study design
Single centre prospective cohort study. Chronic hepatitis B patients who
experience a flare after stopping nucleos(t)ide analogue therapy will undergo
peripheral blood collections every 2-4 weeks for a maximum period of 6 months
in order to characterize the intrahepatic immune response and gene expression
profile.
Study burden and risks
Patients enrolled in this study and will not directly benefit from this study.
During the course of the study peripheral blood collections will be performed
every 2-4 weeks 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
• Age between 18 and 65.
• Previously diagnosed with chronic HBV.
• Treated with entecavir or tenofovir.
• Flare defined as ALT>=2x upper limit of normal.
• Written informed consent.
Exclusion criteria
• 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 | NL77987.078.21 |