LAUSR

BACKGROUND & AIMS Hepatitis B vaccine has been included in the infant immunization schedule since 1991 in the US. We aimed to assess its effectiveness against hepatitis B virus (HBV) infection and its impact on mortality. APPROACH & RESULTS The study population was participants aged 6+ years with HBV vaccination history and an HBV serologic testing from National Health and Nutrition Examination Survey, 1999-2018. Participants aged 18+ years with linked mortality records from 1999-2014 were followed for mortality analysis. Multivariable logistic regression was used to compute vaccine effectiveness (VE) overall, by year of birth, and age. Cox regression was used to estimate hazards ratios (HRs) for all-cause, cancer-related, and cardiovascular-related mortality. A total of 64107 participants were included in the main analysis with 29600 (40.7%) completed HBV vaccine (>=3 dose, vaccinated). The highest vaccination uptake was found among those born after 1991 at 86.5%. Vaccinated participants had higher prevalence of vaccine-induced immunity than unvaccinated (47.2% vs 7.4%). Among those born after 1991, VE was found at 58% (95% CI, 18%-79%) overall and 85% for those aged >=20 years (mean age, 22), whereas no effect was found among those born prior to 1990. HBV vaccination was associated with reduced risk of all-cause mortality (HR=0.78, 95% CI, 0.68-0.90) and cancer-related mortality (HR=0.76, 95% CI, 0.58-1.00) but not for cardiovascular-related mortality. CONCLUSION In universal infant vaccination era, HBV vaccine showed substantial effectiveness against HBV infection and maintained strong protection for 20 years. It was also associated with reduced risk of all-cause and cancer-related mortality.