Hepatitis B e antigen loss in adults and children with chronic hepatitis B living in North America: A prospective cohort study

for the Hepatitis B Research Network (HBRN)

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB). Among children and adults with CHB and without HIV, HCV or HDV co-infection enrolled in the Hepatitis B Research Network prospective cohort studies, 819 were HBeAg positive at their first assessment (treatment naïve or >24 weeks since treatment). Of these, 577 (200 children, 377 adults) were followed every 24–48 weeks. HBeAg loss was defined as first HBeAg-negative value; sustained HBeAg loss was defined as ≥2 consecutive HBeAg-negative values ≥24 weeks apart. During a median follow-up of 1.8 years, 164 participants experienced HBeAg loss, a rate of 11.4 (95% CI, 9.8–13.3) per 100 person-years. After adjustment for confounders, HBeAg loss rate was significantly higher in males than females, in older than younger individuals, in Whites or Blacks than Asians, in those with genotype A2 or B versus C, and in those with basal core promoter/pre-core mutations versus wild type. Additionally, during follow-up, an ALT flare and a lower quantitative HBsAg, quantitative HBeAg or HBV DNA level predicted higher rates of HBeAg loss. The majority (88%) with HBeAg loss had sustained HBeAg loss. In conclusion, a number of specific demographic, clinical and viral characteristics impacted rate of HBeAg loss and may prove useful in design and interpretation of future therapeutic studies.

Original languageEnglish (US)
Pages (from-to)1526-1538
Number of pages13
JournalJournal of Viral Hepatitis
Issue number11
Early online dateAug 6 2021
StatePublished - Nov 2021

Bibliographical note

Funding Information:
The HBRN was funded as a Cooperative Agreement between the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the following investigators: Lewis R. Roberts, MB, ChB, PhD (U01‐DK082843), Anna Suk‐Fong Lok, MD (U01‐DK082863), Steven H. Belle, PhD, MScHyg (U01‐DK082864), Kyong‐Mi Chang, MD (U01‐DK082866), Michael W. Fried, MD (U01‐DK082867), Adrian M. Di Bisceglie, MD (U01‐DK082871), William M. Lee, MD (U01‐DK082872), Harry L. A. Janssen, MD, PhD (U01‐DK082874), Daryl T‐Y Lau, MD, MPH (U01‐DK082919), Richard K. Sterling, MD, MSc (U01‐DK082923), Steven‐Huy B. Han, MD (U01‐DK082927), Robert C. Carithers, MD (U01‐DK082943), Mandana Khalili, MD (U01‐DK082944), Kathleen B. Schwarz, MD (U01‐DK082916), an interagency agreement with NIDDK: Lilia M. Ganova‐Raeva, PhD (A‐DK‐3002‐001) and support from the intramural program, NIDDK, NIH: Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong‐Mi Chang, MD, the Immunology Center, (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01‐RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Norah A. Terrault, MD, MPH (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), Anna Suk‐Fong Lok (CTSA Grant Number UL1RR024986, U54TR001959), and Kathleen B. Schwarz, MD (CTSA Grant Number UL1TR000423). Additional support was provided by Gilead Sciences, Inc. and Roche Molecular Systems via a CRADA through the NIDDK. The investigators recognize and appreciate the contributions of the HBRN participants without whom this research would not be possible

Funding Information:
Dr. Lee receives research support from Merck, Conatus, Intercept, Bristol‐Myers Squibb, Novo Nordisk, Synlogic, Eiger, Cumberland, Exalenz, Instrumentation Laboratory and Ocera Therapeutics, now Mallinckrodt Pharmaceuticals. He has consulted for Novartis, Sanofi and Genentech and Seattle Genetics. Dr. King receives grant support from Abbott. Dr. Feld receives research support from Abbvie, Enanta, Gilead, Janssen and consults for Abbvie, Gilead, GSK, Roche. Dr. Fontana has received research support from Gilead, Abbvie and Bristol Myers Squibb (BMS). Dr. Janssen reports receiving consultant fees and/or grant support from BMS, AbbVie, Gilead Sciences, Novartis, Roche, Janssen, Arbutus, VIR and Merck. Dr. Sterling receives grant support from Roche, Abbott, Abbvie and Gilead. Dr. Di Bisceglie consults for Gilead and BMS. Dr. Ghany, Dr. Mogul and Ms. Wang have no conflicts to disclose.

Publisher Copyright:
© 2021 John Wiley & Sons Ltd.


  • e antigen
  • hepatitis B
  • prospective cohort


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