Trial Information

Observational Study of Persons With Hepatitis B Virus Infection in North America (Cohort Study)

AIMS

Primary Aim:

- 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 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, HBeAg negative, have normal 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.

Type of Study:

Observational

Cohort Study

Patients with HBV infection will be identified by sites participating in the NIH-funded
Hepatitis B Research Network (HBRN). Consenting patients who meet entry criteria will
undergo a baseline evaluation. Those who are eligible for one of the treatment studies being
conducted by the network will be approached about participating. If they are not eligible,
unwilling to participate or have completed their participation in a treatment study, they
will be followed longitudinally to observe clinical outcomes and changes in their virologic
and immunologic status.

It is estimated that approximately 2,500 participants with HBV infection will be enrolled
over a period of approximately 24 months. They will be followed indefinitely until the
conclusion of the study, which is estimated presently to be up to 72 months.

Inclusion Criteria

- Written informed consent

- At least 18 years of age

- HBsAg-positive

Exclusion Criteria

- History of hepatic decompensation based on clinical or laboratory criteria

- Hepatocellular carcinoma (HCC)

- History of solid organ transplantation or bone marrow transplantation

- Current hepatitis B antiviral treatment (except pregnant women)

- Chronic immunosuppression therapy

- Known HIV co-infection (patients with HDV or HCV co-infection are not excluded)

- Medical or social condition which, in the opinion of the investigator, would make the
patient unsuitable for the study or interfere with or prevent follow up per protocol.

- Unable or unwilling to return for follow-up visits

Briefly, the standard visit schedule for participants will be at baseline, weeks 12, 24 and
48 in their first year of enrollment and every 24 weeks in subsequent years.

Variable follow up visits may be required if certain events are encountered. For example,
for participants experiencing an ALT flare, as defined in section 3.2.1 and Appendix A,
follow up will occur every 2-4 weeks until resolved and for HBeAg or HBsAg loss,
participants will be asked to return in 12 and 24 weeks, and then resume follow-up of every
24 weeks.

The following events will be noted:

- ALT flare

- HBsAg or HBeAg loss

- Cirrhosis

- Hepatic decompensation

- HCC

- Liver transplantation

- Death

For women who are, or become, pregnant while enrolled in the cohort study, one visit will
occur early in pregnancy (1st or 2nd trimester) and one later in pregnancy (at or after 28
weeks gestation). Such visits may coincide with a regularly scheduled visit or may be an
additional visit. Following delivery, extra data will be collected at 12, 24, and 72 weeks
post delivery (see Appendix E), either at a regularly scheduled visit or at a special visit.