Clinical Trials

Aims - Primary Aim: o To describe participants with hepatitis B virus (HBV) infection in a prospective cohort in the United States (US) and Canada and identify predictors of disease activation and progression - Secondary Aims: - To describe clinical, virological, and immunological characteristics of participants with HBV in the US and Canada - To evaluate changes in HBV infection status and quantitative hepatitis B surface antigen (HBsAg) levels and factors associated with those changes - To verify whether a baseline HBsAg below 1,000 IU/mL and HBV DNA below 1,000 IU/mL is an accurate predictor of people who are, or who will become, inactive carriers, defined as people who are HBsAg positive, hepatitis B "e" antigen (HBeAg) negative, have normal Alanine transaminase (ALT) and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months - To develop a bank of biospecimens (e.g., serum, plasma, DNA, lymphocytes, liver tissue) obtained from participants with HBV infection - To identify participants with HBV infection who are potential candidates in one of the treatment studies to be conducted by the Hepatitis B Research Network (HBRN) - To describe the natural history of hepatitis B infection in pregnancy including the frequency of, and clinical and virological characteristics associated with, hepatic flares during pregnancy and post-partum.

The objective of this study is to compare the long-term efficacy of treatment with combination therapy with peginterferon plus tenofovir versus tenofovir monotherapy in the treatment of chronic hepatitis B. This is a randomized (1:1) parallel group design trial comparing (i) Tenofovir DF 300 mg daily for 192 weeks (4 years) and (ii) peginterferon alfa-2a 180 µg weekly for 24 weeks plus Tenofovir DF 300 mg daily for 192 weeks (4 years). Enrolled participants will be stratified by HBeAg status (positive/negative), genotype (A vs. all others) and cirrhosis (present vs. absent). After 192 weeks of treatment, participants meeting criteria for treatment discontinuation will stop treatment and be followed for 48 weeks (total duration of treatment and follow up is 240 weeks). A liver biopsy will be obtained at the end-of-treatment (week 192) to assess improvement in histology. Emtricitabine/tenofovir coformulated as Truvada, approved for treatment of HIV but not for treatment of HBV infection, will be offered to patients with primary nonresponse, partial virological response or confirmed virologic breakthrough.

Aim 1: The clinical and virological status of chronic Hepatitis B (HBV) infection is defined by distinct patterns of immune effector and regulatory responses: The investigators propose that one or more immune regulatory are induced during chronic hepatitis B that define the extent of immune tolerance vs. activation with associated disease activity and viremia. Towards this end, 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 will be examined in a cross-sectional manner in patients with chronic HBV and control groups. Aim 2: Clinical hepatitis flares during chronic hepatitis B reflect altered balance between immune regulatory and effector responses.

To determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B "e" antigen (HBeAg) positive adults who are in the immune tolerant phase. To evaluate "off treatment" sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase. A randomized (1:1) controlled trial of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon alfa-2a in adults with HBeAg-positive chronic hepatitis B with normal or near normal ALT levels and high serum levels of HBV DNA ("immune tolerant" HBeAg-positive chronic hepatitis B) compared to no treatment. A similar study will be conducted in children. Participants in this adult study will be stratified according to age (18-30, >30-40) and center. All participants will be followed until week 96 (48 weeks after discontinuation of therapy in the treatment group) at which time the primary outcome will be measured.