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Citation
Belle, Steven (2024). Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B (HBRN Immunology Cohort) (Version 1) [Dataset] NIDDK Central Repository. https://doi.org/10.58020/n50b-rk65
Data Availability Statement
Data from the Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B (HBRN Immunology Cohort) [(Version 1) https://doi.org/10.58020/n50b-rk65] reported here are available for request at the NIDDK Central Repository (NIDDK-CR) website, Resources for Research (R4R), https://repository.niddk.nih.gov/.
Acknowledgment Statement
The HBRN Immunology Cohort study was conducted by the study investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The resources from the HBRN Immunology Cohort study reported here were supplied by NIDDK Central Repository (NIDDK-CR) and are available for request at https://repository.niddk.nih.gov. This manuscript was not prepared under the auspices of the HBRN Immunology Cohort study and does not necessarily reflect the opinions or views of the HBRN Immunology Cohort study, NIDDK-CR, or NIDDK.
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General Description

Hepatitis B, a significant cause of cirrhosis and hepatocellular carcinoma worldwide, affects an estimated 800,000 to 1.4 million people in the United States. While progress has been made in the prevention, diagnosis, and treatment of chronic hepatitis B, challenges remain in identifying persons affected by the virus and in determining recommendations for management and treatment. The Hepatitis B Research Network (HBRN) was a multicenter network to investigate the etiology and progression of the disease, and to test the safety and efficacy of current treatment approaches.

Hepatitis B virus (HBV) is largely a non-cytopathic virus. Therefore, liver disease pathogenesis and viral clearance in HBV infection is believed to be immune-mediated. At the same time, HBV persists with impaired antiviral immune effector responses that are potentially regulated by multiple immune pathways, including the CD28 costimulatory receptors and immune regulatory T cells. The Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B (HBRN Immunology Cohort) study aimed to assess whether the balance between immune regulatory and effector responses in HBV-infected individuals defines the level of viremia, liver inflammation, and treatment outcomes.

Objectives

The clinical and virological status of chronic HBV infection is defined by distinct patterns of immune effector and regulatory responses. This study examined:

  • The immune effector and regulatory responses relative to serum HBV DNA, alanine aminotransferase (ALT), Hepatitis B e antigen (HBeAg), Hepatitis B surface antigen (HBsAg), and liver histology for participants with chronic HBV and in control groups
  • Clinical hepatitis flares that reflect altered balance between immune regulatory and effector responses for chronic HBV participants
Outcome Measure

Outcome measures included immune regulatory and effector responses relative to HBV DNA, ALT, and clinical outcomes. In addition, HBV-specific lymphoproliferative, IFN-gamma and IL 10 responses, T cell activation and costimulatory markers (PD1, CTLA4, CD28, CD127), FoxP3+ Treg frequency, and NK frequency and expression of activating/inhibitory receptors and Dendritic cell frequency.

Eligibility Criteria

Inclusion criteria:

  • 18 years and older
  • Providing informed consent for this ancillary study

Exclusion criteria:

  • Children under 18 years of age, participants with anemia
  • Hgb < 10 or Hct < 30, congestive heart failure or chronic lung disease requiring oxygen, active coronary artery disease with unstable angina, sepsis or renal failure, other significant medical conditions, autoimmune disease or immunosuppression
Outcome

Compared to controls, participants with chronic hepatitis B had weak T cell proliferative, interferon-γ, and interleukin-10 responses to HBV, with increased frequency of circulating FOXP3+CD127− regulatory T cells and CD4+ T cell expression of PD1 and CTLA4. T cell measures did not clearly distinguish between clinical chronic hepatitis B phenotypes, although the HBV core-specific T cell response was weaker in HBeAg+ than HBeAg− participants. Although in vitro blockade of PD1 or CTLA4 increased T cell responses to HBV, the effect was weaker in HBeAg+ than HBeAg− participants. Furthermore, T cell responses to influenza and lipopolysaccharide were weaker in chronic hepatitis B participants than controls.

Research Area

Liver Disease

Study Type

Observational

Study Sites

10

Study Start Date

2011-02

Study End Date

2024-12

Condition

Hepatitis B Virus Infection

Keywords

Viremia, Liver Inflammation, Chronic Hepatitis B Virus (HBV) Infection, HBV DNA, Clinical Hepatitis Flares, Alanine Aminotransferase (ALT), Ancillary Study, Disease Etilogy, Immune Regulatory Response, Immune Effector Response, Disease Progression

NIDDK Division

DDN

1,090
Participants

Target Population
Adults
Sex statistics is not available for this study
Age statistics is not available for this study
Race statistics is not available for this study
Ethnicity statistics is not available for this study
Location statistics is not available for this study

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Datasets (6)
Datasets Table
Dataset Name
Description
# of Records
# of Variables
File Format(s)
Immunology Criteria Dataset
Captures study inclusion and exclusion criteria. Only required at sites participating in the Immunology Ancillary study. Refer to protocol for participating sites.1105sas7bdat (384 KB); csv (101.59 KB)
Immunology Cohort Controls Lab Results Ancillary Dataset
Result file of controls from the immunology lab20sas7bdat (512 KB); csv (39.27 KB)
Immunology Cohort Cumulative Lab Results Ancillary Dataset
Cumulative result file from the immunology lab478sas7bdat (1.97 MB); csv (654.99 KB)
Luminex Ancillary Dataset
Luminex data for plasma levels of 28 cytokines/chemokines77sas7bdat (204 KB); csv (28.37 KB)
CD3hiCD4 - T-Cell Ancillary Dataset
CD3hiCD4 - T-cell analysis74sas7bdat (128 KB); csv (13.33 KB)
Immunology Cohort Received Samples Ancillary Dataset
Log file of samples sent and received at the immunology lab for the cohort protocol478sas7bdat (128 KB); csv (25.7 KB)
Specimens (0)
There are currently no specimens available