Economic evaluation of delaying the infant hepatitis B vaccination schedule

Abstract Introduction Children who acquire hepatitis B virus (HBV) infection in early childhood through perinatal, household or community exposures are at highest risk of all age groups for experiencing chronic infection and premature death. Universal administration of hepatitis B (HepB) vaccine for all infants <24 hours of birth and completing the childhood series remains the cornerstone for HBV elimination efforts in the United States. We evaluated the health and economic impact of delaying HepB vaccination among U.S. infants. Methods We constructed a Markov model to simulate lifetime health outcomes and costs for the 3,628,934 infants born in the United States in 2024 for HBV infections acquired up to age 18 years. The model incorporated hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) prevalence among birthing parents, percentage of pregnant parents tested for HBsAg during pregnancy or at delivery, vertical/perinatal and household/community HBV infection risks among children, and resulting sequalae from chronic infection. Eight delayed vaccination scenarios were evaluated in which the first HepB dose was given at 2 months, 7 months, 4 years, or 12 years, applied either only to infants born to HBsAg-negative birth parent or to both HBsAg-negative and HBsAg-unknown birthing parents. Outcomes included acute and chronic HBV infections, cirrhosis, hepatocellular carcinoma, HBV-related deaths, quality-adjusted life-years (QALYs), life-years, and total healthcare costs from the healthcare system perspective. We modeled scenarios with perfect and imperfect adherence to the HepB vaccination schedule, and scenarios with or without additional HBV screening costs for those with delayed receipt of HepB vaccine. Results All delayed vaccination scenarios resulted in more infections, worse health outcomes, and higher costs than the current universal birth dose recommendation. Under perfect adherence, delaying HepB vaccination by 2 months for infants of HBsAg-negative parents led to an additional 90 acute infections, 75 chronic infections, 29 HBV-related deaths, with $16.4 million in added costs for infants born during one year. Delaying to 12 years resulted in an additional 190 acute infections, 50 deaths, and nearly $30 million in added costs. Delaying HepB vaccination to 12 years for infants of both HBsAg-negative and HBsAg-unknown parents resulted in an additional 2,351 acute infections, 744 deaths, and $368 million in excess costs. Imperfect adherence to the vaccination schedule amplified all negative outcomes substantially. Incorporating pre-vaccination serologic screening for delayed schedules markedly increased total costs. Conclusions Even brief delays in HepB vaccine initiation substantially increase HBV infections, adverse health outcomes, and health system costs. Our results quantify and demonstrate the importance of the universal HepB birth dose in preventing perinatal and early childhood HBV transmission in the United States. Summary We constructed a Markov model to evaluate health and economic outcomes for the 3.6 million infants born in 2024 under eight scenarios that delayed the first hepatitis B (HepB) vaccine dose to 2 months, 7 months, 4 years, or 12 years. All delayed schedules increased acute and chronic infections, HBV-related deaths, and healthcare costs compared with the current universal HepB birth-dose policy. For a single year of delaying the HepB birth dose to 2 months among infants whose birth parents are not known to be living with hepatitis B, we estimate 1,437 preventable hepatitis B infections among children, 304 cases of liver cancer, 482 HBV-related deaths, and over $222 million in excess healthcare costs. For a single year of delaying the HepB birth dose to 12 years among infants whose birth parents are not known to be living with hepatitis B, we estimate 2,726 preventable hepatitis B infections among children, 503 cases of liver cancer, 788 HBV-related deaths, and over $313 million in excess healthcare costs. Our results demonstrate and quantify the critical role of timely universal HepB birth dose vaccination in preventing childhood HBV transmission.