Hepatitis B Virus Infection Status in Japanese Children Prior to Universal Vaccination: Sustained Effectiveness of Mother‐to‐Child Transmission Prevention and Residual Infection Burden

AIM: To evaluate the effectiveness of prevention of mother-to-child transmission (PMTCT) over 25 years, we conducted a nationwide epidemiological survey through a comprehensive assessment of hepatitis B virus (HBV) markers. METHODS: Two cohorts were recruited before universal vaccination: children aged 9-10 years undergoing school health checkups (Group 1) and hospital patients 0-15 years of age from 11 hospitals across Japan to assess age and regional differences (Group 2). Hepatitis B surface antigen (HBsAg) and core antibody (anti-HBc) were measured in both cohorts. HBV-DNA was tested to evaluate occult HBV infection and viral genotypes in Group 2. Anti-HBs antibody was measured to estimate HBV vaccine coverage. RESULTS: In Group 1 and Group 2, 8125 and 8453 samples were collected, respectively. HBsAg prevalence was 0% in Group 1 and 0.047% in Group 2 using a conventional assay (Lumipulse II HBsAg). Most HBsAg-positive samples were from children < 4 years. HBsAg-negative and anti-HBc-positive samples were detected in 0.42% of Group 1 and 0.95% of Group 2. Among these samples in Group 2, 10.3% were HBV-DNA-positive, indicating occult HBV infection. Genotype C predominated; however, four genotype D cases were identified in Hokkaido. Anti-HBs positivity among HBV-uninfected samples at ages 1, 2, 5, 10, and 15 years was 53.4%, 27.5%, 7.5%, 5.6%, and 1.9%, respectively. CONCLUSIONS: Following the implementation of PMTCT measures in Japan, the prevalence of HBsAg-positive children was extremely low. However, the prevalence of occult infection and anti-HBc positivity indicated that some children remained exposed to HBV. To further eradicate HBV infection, universal vaccination was introduced nationwide in 2016.