Hepatitis B Research Network Adult Cohort Study (HBRN Cohort A)

General Description

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. While progress has been made in the prevention, diagnosis, and treatment of chronic hepatitis B, challenges remain in identifying persons affected by the virus and in determining recommendations for management and treatment. 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 Adult Cohort Study (HBRN Cohort A) was designed to describe participants with hepatitis B virus (HBV) infection and identify predictors of disease activation and progression. The relationship of HBV genotype to clinical, biochemical, and histological characteristics and to pregnancy was also explored.

Individuals of at least 18 years of age that were hepatitis B surface antigen (HBsAg) positive were enrolled in the HBRN Adult Cohort study. Baseline data were collected on demographics, medical history, family history of liver disease, and health behaviors. Participants were categorized into various phases of HBeAg-positive and HBeAg-negative HBV infection and stages of HBV disease for monitoring of changes in HBV infection status and quantitative HBsAg levels. 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 (HCC), death, and liver transplantation—and the factors associated with these outcomes were assessed as primary outcome measures, evaluated at up to 288 weeks. Analyses were performed to determine whether a baseline HBsAg below 1,000 IU/mL and HBV DNA below 1,000 IU/mL were accurate predictors of people who were inactive carriers (defined as people who were HBsAg positive, HBeAg negative, had normal ALT and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months with HBV DNA under 1,000 IU/mL). Additionally, biospecimens were collected from participants to create a repository of resources for future studies.

Objectives

The primary aims of the HBRN Adult Cohort Study were to describe participants with hepatitis B virus (HBV) infection and identify predictors of disease activation and progression. The relationship of HBV genotype to clinical, biochemical, and histological characteristics and to pregnancy was also explored.

Outcome Measure

The rate of various clinical outcomes—including hepatitis exacerbation marked by ALT flare, antigen loss of HBsAg or HBeAg, cirrhosis, development of hepative decompensation, hepatocellular carcinoma, death, and liver transplantation—and the factors associated with these outcomes were assessed as primary outcome measures.

Criteria

Inclusion criteria:

• Written informed consent
• At least 18 years of age
• Hepatitis B surface antigen (HBsAg) positive and either:
• Pregnant
• Anti-Hepatitis D positive
• Diagnosed with acute Hepatitis B infection or experiencing a hepatitis flare
• Immune tolerant or immune active phenotype
• Potentially eligible for the Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B ancillary study (NCT01298037)

Exclusion criteria:

• Hepatic decompensation
• Hepatocellular carcinoma (HCC)
• Liver transplantation
• Current hepatitis B antiviral treatment (except pregnant women and patients who were anti-HDV positive)
• Known human immunodeficiency virus (HIV) co-infection (patients with Hepatitis D (HDV) or Hepatitis C (HCV) co-infection were not excluded)
• Medical or social condition which in the opinion of the investigator would interfere with or prevent follow-up per protocol
• Unable or unwilling to return for follow-up visits

Outcome

The study found that over the course of follow-up, the rate of adverse outcomes was low (2% at 7 years) among this large cohort of mostly untreated patients with inactive chronic HBV infection. Additionally, the study highlights the benefits of HBsAg loss and further indicates the importance of early diagnosis and subsequent treatment to prevent adverse outcomes.