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.

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

The study population will be recruited from multi-site clinical centers in the United States and Canada including primary care hospitals and community centers that have enrolled into the HBRN clinical trials (NCT01369212 or NCT01369199).