Age, Race and Viral Genotype are Associated With the Prevalence of Hepatitis B E Antigen in Children and Adults With Chronic Hepatitis B

Adrian M. Di Bisceglie; Wendy C. King; Mauricio Lisker-Melman; Mandana Khalili; Steven H. Belle; Jordan J. Feld; Marc G. Ghany; Harry L. A. Janssen; Daryl Lau; William M. Lee; Simon C. Ling; Stewart Cooper; Philip Rosenthal; Kathleen B. Schwarz; Richard K. Sterling; Jeffrey H. Teckman; Norah Terrault; for the Hepatitis B Research Network (HBRN)


J Viral Hepat. 2019;26(7):856-865. 

In This Article

Abstract and Introduction


Hepatitis B e antigen (HBeAg) is an important serological marker of hepatitis B virus (HBV) infection and is associated with higher levels of viraemia, increased risk of infectivity to others and increased risk of hepatocellular carcinoma. We analysed HBeAg status in a large cohort of adults and children enrolled in Cohort Studies of the Hepatitis B Research Network, long-term natural history studies of chronic HBV infection. A cross-sectional analysis examined factors associated with HBeAg positivity, including demographic and virologic data, across the age spectrum. Among 2241 enrolled participants who met criteria for this analysis, 825 (37%) were seropositive for HBeAg. The prevalence of HBeAg was lower in those with older age, ranging from 85% among those up to 10 years of age to only 12% among those older than 50 years. In addition to age, both race and HBV genotype were independently associated with HBeAg positivity. There was a significant interaction between age and race; the prevalence of HBeAg was significantly higher among Asians > 10-30 years old vs Whites or Blacks who were >10 to 30 years old and those infected with HBV genotype C. Conversely, the presence of the basal core promoter and precore variants was associated with significantly lower prevalence of HBeAg, even when adjusted for age, race and genotype. These data will provide a better understanding of factors associated with seropositivity for HBeAg and may lead to better strategies for preventing HBV infection and broader indications for antiviral therapy.


Approximately 257 million individuals around the world are chronically infected with the hepatitis B virus (HBV) putting them at risk of progressive liver disease and hepatocellular carcinoma (HCC).[1] Despite the availability of an effective vaccine, the worldwide prevalence of HBV has remained unchanged because of the incomplete uptake of vaccine leaving a large reservoir of infected persons. Antiviral therapies are effective in controlling HBV, but rarely eliminate the infection. Not all infected persons are eligible for, or have access to, antiviral therapies, and hence, it remains important to have the best possible understanding of the natural history of chronic HBV infection. Although HBV is endemic in East Asia and sub-Saharan Africa, migration patterns over the last several decades have led to a large number of HBV-infected immigrants and refugees living in North America, and the nature of their infection and its natural history has been incompletely studied.[2,3]

Hepatitis B e antigen (HBeAg) is a key serological marker of HBV infection and has been associated with higher levels of HBV viraemia, infectivity and increased risk of HCC.[4–9] Furthermore, clearance of HBeAg is thought to be associated with improved outcomes. The primary aim of this study was to identify viral and host factors related to HBeAg seropositivity in a cross-sectional analysis of a large cohort of adults and children with chronic HBV infection living in the United States or Canada. In addition, the association of age with serum levels of HBeAg, HBV DNA and HBsAg among those with HBeAg seropositivity was examined.