The impact of hepatitis B vaccination in the United States, 1999-2018

Background and Aims Hepatitis B vaccine has been included in the infant immunization schedule since 1991 in the United States. We aimed to assess its effectiveness against HBV infection and its impact on mortality. Approach and Results The study population was participants aged 6+ years with an HBV vaccination history and an HBV serologic test from the 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 by age. Cox regression was used to estimate HRs for all-cause, cancer-related, and cardiovascular disease-related mortality. A total of 64,107 participants were included in the main analysis, with 29,600 (40.7%) having completed HBV vaccination (three or more doses, 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 the 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 disease-related mortality. Conclusion In the universal infant vaccination era, the HBV vaccine has shown 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.