Incorrect Expansion of a Term and Other Clarifications
Authors: Lydia Tang, Shyam Kottilil
Journal: JAMA (2018)

In Reply The e in HBeAg has been referred to as an abbreviation for "envelope" in several recent studies.Magnius and Espmark 1 first described a new antigenic specificity in individuals positive for Australia antigen (now known as HBsAg) and proposed the designation of e for this new specificity.Although they did not state what the e stood for, others have reported that Magnius and Espmark meant for it to be a standalone e. 2 Because the earliest publications do not refer to the e antigen as standing for envelope, we conclude that it does not.The review article has been corrected online and a correction notice appears in this issue.It is known that the e antigen is secreted and is a nonstructural protein that is not required for viral replication.After its discovery, experiments have demonstrated the release of e antigen from intact virions treated with detergent, suggesting that it exists within intact virions. 3The e antigen has been both included (usually in the space between the nucleocapsid core and the outer envelope) and excluded from illustrations of the HBV virion, and there is no evidence that definitively supports either model.The interpretation of isolated anti-HBc included in Table 3 in the article 4 defines the 2 possible serological windows in acute HBV infection.Dr Zhou is correct in pointing out that anti-HBc would not be detected prior to the appearance of HBsAg.This was included in error and has been corrected in the review article and we apologize for any confusion that this may have caused.Discussion as to the role of vaccination in preventing chronic HBV infection was beyond the scope of the review. 4 An anti-HBs titer greater than 10 IU/L after HBV vaccination is considered a protective response.Anti-HBs titers decrease over time, and we agree that current observational data indicate that the anamnestic response (immune memory) remains even if the titer has decreased to less than 10 IU/L.Therefore, in immunocompetent individuals with confirmed protective response after vaccination, rechecking anti-HBs titers is not indicated.However, anti-HBs titers are not routinely checked after vaccination; therefore, a protective response is not always confirmed.Furthermore, HBV infections were reported in large observational cohorts of individuals despite vaccination as infants (0.44% in 20 634 individuals up to 23 years after vaccination). 5Therefore, there still appears to be a role for screening high-risk patient groups for both chronic HBV infection and evidence of immunity with anti-HBs.The role of revaccination among high-risk individuals with anti-HBs less than 10 IU/L still needs to be addressed.Our review summarized evidence from randomized clinical trials; therefore, we reported the primary outcomes and intention-to-treat analyses of these trials.A recent trial reported no significant difference in transmission with perinatal tenofovir disoproxil compared with placebo (0 of 147 compared with 3 of 147 infants; P = .12). 6 Therefore, the role of antiviral therapy in pregnancy in reducing mother-to-infant transmission of HBV remains controversial.