Effects of T-bet B Cells in Persistent Virus Control After Discontinuance of NAs in CHB Patients

Sponsor

Changhai Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT06029634

Collaborator

(none)

Enrollment

Location

37.6

Actual Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The immune mechanism of the nucleos(t)ide analogs (NAs) in inhibiting HBV replication effectively while having a low sustained virus control rate after drug withdrawal is unclear. B cell immunity and antibody response are the keys to prevent HBV reinfection and keep the virus under control. T-bet+ B, which can be regulated by IL-21, is a newly discovered major effector B cell in protection of pathogens and it is a main subtype of HBsAg-specific B cells. Thus, we suspect that T-bet+ B may play a role in ongoing controlling of the virus after withdraw of NAs in CHB patient. Based on our previous studies on CHB immunity, we use the RNAseq analyse, flow cytometry, and Elispot assay to analyze the frequency, function, and phenotype of B cells in CHB patients with different profiles after withdraw of NAs.

Condition or Disease	Intervention/Treatment	Phase
Chronic HBV Infection Drug Withdrawal	Diagnostic Test: T-bet B cell

Study Design

Study Type:

Observational

Actual Enrollment :

45 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Effects of T-bet B Cells in Persistent Virus Control After Discontinuance of NAs in CHB Patients

Actual Study Start Date :

Jul 1, 2020

Actual Primary Completion Date :

Aug 10, 2023

Actual Study Completion Date :

Aug 20, 2023

Arms and Interventions

Arm	Intervention/Treatment
virologic breakthrough CHB patients withdraw NAs with virologic breakthrough	Diagnostic Test: T-bet B cell The frequency, function, and phenotype of T-bet B cells was tested
virologic response CHB patients withdraw NAs with virologic response	Diagnostic Test: T-bet B cell The frequency, function, and phenotype of T-bet B cells was tested
healthy group The healthy (non-HBV infected) group completed a standard HBsAg vaccination scheduled before entering the study	Diagnostic Test: T-bet B cell The frequency, function, and phenotype of T-bet B cells was tested

Arm

Intervention/Treatment

virologic breakthrough

CHB patients withdraw NAs with virologic breakthrough

Diagnostic Test: T-bet B cell

The frequency, function, and phenotype of T-bet B cells was tested

virologic response

CHB patients withdraw NAs with virologic response

Diagnostic Test: T-bet B cell

The frequency, function, and phenotype of T-bet B cells was tested

healthy group

The healthy (non-HBV infected) group completed a standard HBsAg vaccination scheduled before entering the study

Diagnostic Test: T-bet B cell

The frequency, function, and phenotype of T-bet B cells was tested

Outcome Measures

Primary Outcome Measures

phenotype of B cells [PBMC were collected 0、4、12、24 week after withdraw the NAs]
CD19+cells were sorted from different samples, the frequency, function, and phenotype of B cells were analyzed.
B cell ELISPOT assay [Cells were stimulated with R-848 (1 μg/ml) and IL-2 (10 ng/ml) for 5 days at 37 °C to aid memory B cell differentiation]
Sorted B cell subsets were stimulated for 5 days following which B cell ELISPOT was conducted.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18 to 70 years old, no gender restriction, serum HBsAg positive than 6 months, can understand and sign informed consent, good compliance.

Exclusion Criteria:

coinfected with other hepatotropic virus such as hepatitis C virus,hepatitis D -virus,hepatitis E and hepatitis A etc; coinfected with HIV, markers such as ceruloplasmin, anti-nuclear antibodies and anti-mitochondrial antibodies for co-existent autoimmune and metabolic liver diseases were positive, with hepatocellular carcinoma(HCC) with uncontrollable extrehepatic disease, received glucocorticoid or other immune inhibitor therapy, pregnancy