The Hepatitis B Research Network (HBRN) was a multicenter network to investigate the etiology and progression of the disease and to test the safety and efficacy of current treatment approaches. The HBRN Pediatric Cohort Study (HBRN Cohort P) was designed to describe participants 6 months to <18 years of age 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. Additionally, biospecimens are collected from participants to create a repository of resources for future studies.

The primary objectives of the study were to investigate the natural history of the disease and to identify predictors of disease activation and progression in children. Specifically, the study aimed to describe the clinical, virological, and immunological characteristics of participants with HBV; evaluate changes in HBV infection status and hepatitis B surface antigen (HBsAg) levels and factors associated with those changes; and assess the health-related quality of participants.

The rate of various clinical outcomes—including hepatitis exacerbation marked by alanine aminotransferase (ALT) flare, antigen loss of HBsAg or HBeAg, cirrhosis, development of hepative decompensation, heptaocellular carcinoma, death, and liver transplantation—and the factors associated with these outcomes are assessed as primary outcome measures, evaluated at 72 weeks.

Inclusion Criteria:

• Written informed consent/assent as appropriate
• At least 6 months to <18 years of age
• Hepatitis B surface antigen (HBsAg) positive

• Hepatic decompensation
• Hepatocellular carcinoma (HCC)
• Liver transplantationy
• Current Hepatitis B antiviral treatment (except pregnant females)
• Known coinfection with HIV (patients with hepatitis D or hepatitis C coinfection are not excluded)
• Medical or social condition which in the opinion of the principal investigator would interfere with or prevent regular follow up.
• Unable or unwilling to return for regular follow-up

Among children followed, elevated alanine aminotransferase (ALT) levels were present in 72% at last evaluation, including in 60% of children with loss of hepatitis B e antigen during follow-up and 70% of those who were hepatitis B e antigen negative at baseline. Significant ALT flares occurred in 13 children and of 129 children who fulfilled the American Association for the Study of Liver Diseases treatment criteria during follow-up, anti-HBV treatment was initiated in only 25.