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. Liver disease pathogenesis and viral clearance in hepatitis B virus (HBV) infection is believed to be immune-mediated, defined by distinct patterns of immune effector and regulatory responses. The Immune Regulation and Costimulation in Natural History and Therapeutic Outcome of Chronic Hepatitis B study was designed to examine the effects of antiviral therapy in host immune phenotype and to investigate if antiviral immune responses before, during, and after therapy can predict long term therapeutic response. This study is ancillary to two clinical trials conducted by the Hepatitis B Research Network, titled Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B and Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B. It is hypothesized that therapeutic HBV suppression will enhance antiviral immune effector responses and reduce immune inhibitory factors in participants with chronic hepatitis B.

Participants for the Immune Regulation and Costimulation study are recruited from individuals who are enrolled in the HBRN clinical trials of adults with chronic hepatitis B. Immune regulatory and effector responses relative to serum HBV DNA, alanine aminotransferase (ALT), and clinical outcome are assessed as primary outcome measures. Specifically, IFN-gamma and IL 10 responses, T cell activation and costimulatory markers (PD1, CTLA4, CD28, CD127), FoxP3+ Treg frequency, dendritic cell frequency, and NK frequency are evaluated as measures of immune response. These measures are evaluated throughout the course of the two clinical trials until the termination of the treatment studies.

The study aims to examine the effects of antiviral therapy in host immune phenotype and to investigate if antiviral immune responses before, during, and after therapy can predict long term therapeutic response.

Immune regulatory and effector responses relative to serum HBV DNA, alanine aminotransferase (ALT), and clinical outcome are assessed as primary outcome measures. Specifically, IFN-gamma and IL 10 responses, T cell activation and costimulatory markers (PD1, CTLA4, CD28, CD127), FoxP3+ Treg frequency, dendritic cell frequency, and NK frequency are evaluated as measures of immune response. These measures are evaluated throughout the course of the two clinical trials until the termination of the treatment studies.

Individuals from the HBRN adult clinical trials are enrolled after providing informed consent.

This study is ongoing.