HBRN: Immune Regulation and Costimulation in Natural History and Therapeutic Outcome of Chronic Hepatitis B

N/AActive Not RecruitingNCT01796457

University of Pennsylvania40 enrolled

Overview

This is an ancillary to the NIDDK-sponsored treatment trials titled: Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B (NCT01369212) and Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B (NCT01369199). This study will examine the balance between immune regulatory and effector responses in hepatitis B-infected participants enrolled in the HBRN's clinical trials (NCT01369212 and NCT01369199) to define natural history and treatment outcome.

Aim 1. Therapeutic HBV suppression will enhance antiviral immune effector responses and reduce immune inhibitory factors in participants with chronic hepatitis B. This study will also examine if antiviral therapy has a durable effect in host immune phenotype and define the immunological effect of interferon-alpha (IFNα) therapy in chronic HBV participants. Aim 2. Antiviral immune effector and regulatory responses before, during and/or after therapy can predict long term therapeutic response.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Hepatitis B

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Ability to provide informed consent for participation in the ancillary study Exclusion Criteria: * Children under 18 years of age * Pregnant women * Participants with anemia (Hgb\<10 or Hct\<30) * Participants with active medical conditions such as congestive heart failure or chronic lung disease requiring oxygen, active coronary artery disease with unstable angina, sepsis and renal failure * Participants with significant medical conditions, autoimmune disease or immunosuppression

California Pacific Medical Center

San Francisco, California, United States

University of California San Francisco Medical Center

San Francisco, California, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Minnesota

Plymouth, Minnesota, United States

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Harborview Medical Center

Seattle, Washington, United States

Toronto Western Hospital Liver Centre

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Immune regulatory and effector responses relative to HBV DNA, ALT and clinical outcome

HBV-specific lymphoproliferative, IFN-gamma and IL10 responses, T cell activation and costimulatory markers ( PD1, CTLA4, CD28, CD127), FoxP3+ Treg frequency, and NK frequency and expression of activating/inhibitory receptors Dendritic cell frequency

Time frame: up to 192 weeks