Epidemiologic and economic models for accelerating momentum towards hepatitis B elimination in the United States

Progress towards elimination of hepatitis B in the United States has stalled in recent years. There are 880,000 prevalent cases of chronic hepatitis B in the United States based on data from 2013 to 2018, with a modeled estimate of 1.89 million. It is estimated that 20,700 acute infections occurred in 2019. Vaccination, screening, and linkage to care have been employed as tools to reduce the burden of hepatitis B. Hepatitis B vaccines have demonstrated safety, immunogenicity, and efficacy over the past 40 years. Vaccination is a valuable, yet underutilized tool, in the prevention of hepatitis B among adults in the United States.

The CDC Advisory Committee on Immunization Practices (ACIP) initially recommended the Hepatitis B vaccination in 1982 in the United States for high-risk groups (including, men who have sex with men (MSM), persons who inject drugs (PWID), and heterosexual persons with multiple partners). In 1984, the recommendation was expanded to recommend that all infants born to persons who are infected with the hepatitis B virus receive the hepatitis B vaccine and hepatitis B immune globulin at birth and complete the hepatitis B vaccine series. In 1991 all U.S. infants were recommended to receive hepatitis B vaccination; and in 1999 all unvaccinated children aged <19 years were recommended to receive hepatitis B vaccination. In 2005 universal birth dose vaccination was recommended. These recommendations comprise a comprehensive program of universal childhood vaccination. While coverage of the hepatitis B vaccine has remained high among children (greater than 90%), coverage among adults ≥19 years remains especially low. Self-reported coverage of 3 doses of hepatitis B vaccine was only 30% among adults in 2018. At the same time, there has been an increase in acute hepatitis B in the United States resulting from increases in injection use behaviors.

Chronic hepatitis B could be averted through early diagnosis, monitoring, and treatment. Yet, hepatitis B screening remains low in the United States. Current screening guidelines recommends universal hepatitis B surface antigen screening of all pregnant women and risk-based screening for non-pregnant asymptomatic adults (including non-US born adults from endemic countries with HBsAg ≥2%). According to data from the National Health and Nutrition Examination Survey during 2011-2016, only a third of individuals with chronic hepatitis B are aware of their infection. Between 15% and 25% of cases of undiagnosed and untreated hepatitis B will lead to premature death from liver cirrhosis, liver failure necessitating liver transplant, or liver cancer. Documented barriers to implementing testing include access to non-health information that is not routinely captured in medical records (i.e., place of birth from endemic countries) and triangulation of such information with existing patient medical records.

Several NEEMA studies have addressed key information gaps on the health and economic benefits of intervening along the hepatitis B prevention and care cascade. A recent NEEMA collaboration with the Coalition for Applied Modeling for Prevention (CAMP) addressed the cost of a single-dose hepatitis B revaccination among infants born to hepatitis B-infected mothers not responding to the initial vaccine series. Another NEEMA collaboration with CAMP addressed the cost-utility of universal hepatitis B vaccination among adults. Lastly, a NEEMA collaboration with the Prevention Policy Modeling Lab (PPML) evaluated the impact of universal hepatitis B screening of the adult population in the United States.

  1. Cost Analysis of Single-dose Hepatitis B Revaccination among Infants Born to Hepatitis B-infected Mothers Not Responding to the Initial Vaccine Series
    • The goal of the NEEMA project was to compare a single dose revaccination strategy to the previously recommended three dose revaccination strategy for infants not responding to the initial vaccine series. The primary output of interest is the cost per person calculated from the societal perspective and assuming similar cumulative risk of hepatitis B infection in both strategies. The analysis included three epidemiologic scenarios that varied levels of previous protection among infants indicated for revaccination.
    • Findings from this cost analysis provided options for optimizing the revaccination rates considering previously scheduled well-child physician visits and found that the incremental cost per infant was lowest when all 3 vaccination visits were assumed to occur during a scheduled well-child visit. Specifically, if all three vaccination visits occurred during a previously scheduled well-child visit, a single dose revaccination reduced the cost per individual by $28.29-$52.73 in 2016 USD depending on the scenario. Conversely, if all revaccination vaccine visits were previously unscheduled, the incremental decrease in cost per individual reached $119.81-$155.72 in 2016 USD. Informed by the results from this cost analysis and guided by evidence on the benefit of the additional 3 dose vaccination series among infants not responding to the original series, the ACIP recommended a single-dose revaccination for infants born to HBsAg-positive mothers not responding to the initial hepatitis B vaccine series in January 2018.
  2. Assessing the Cost-Utility of Universal Hepatitis B Vaccination Among Adults
    • This NEEMA study used a decision analytic model with Markov disease progression to explore the implications of prospective universal hepatitis B vaccination among adults with either a 3-dose or a 2-dose vaccine. The model simulated a cohort of one million adults distributed by age and risk groups and quantified the health benefits and costs for each vaccination strategy.
    • This NEEMA study found that universal adult vaccination against hepatitis B may be an appropriate strategy for reducing hepatitis B incidence and improving health outcomes. Compared to the current vaccination coverage, the study determined universal vaccination averted nearly 24.8% of cases of acute hepatitis B in the 3-dose strategy (24.6% in the 2-dose strategy) and 22.8% of hepatitis B related deaths in the 3-dose strategy (22.2% in 2-dose strategy). The cost per quality adjusted life year gained was similar if considering a 2-dose versus a 3-dose vaccination series ($152,722 for the 3-dose and $155,429 for the 2-dose vaccination series in 2019 USD). Findings from this study informed the ACIP conclusion in November 2021 affirming that universal adult vaccination against hepatitis B provides advantages over the previous risk-based approach to adult hepatitis B vaccination.
  3. Cost-Effectiveness of 1-Time Universal Screening for Chronic Hepatitis B Infection in Adults in the United States
    • This NEEMA project evaluated the impact of universal hepatitis B screening of the adult population in the United States. The study used a Markov model to calculate costs, population impact, and cost-effectiveness of a 1-time universal screening compared with current practice.
    • The study found universal hepatitis B screening to be cost saving (assuming 0.24% prevalence of undiagnosed infections) for adults aged 18-69 years. Compared to current practice, universal HBsAg screening would save $262,857 in 2020 USD and would result in a gain of 135 quality adjusted life years per 100,000 adults screened.

    These NEEMA studies address key information gaps on the value of vaccination and screening for hepatitis B. NEEMA recipients and collaborators from NCHHSTP’s Division of Viral Hepatitis continue to work actively to contribute new information to the evidence base to inform future guidelines and recommendations along the hepatitis B prevention and care cascade.

Project Highlights
  • There are 880,000 prevalent cases of chronic hepatitis B in the United States based on data from 2013 to 2018 (modeled estimate of 1.89 million).
  • In 2019, 20,700 acute infections were also estimated to have occurred.
  • Vaccination, screening, and linkage to care have been employed as tools to reduce the burden of hepatitis B.
  • Several NEEMA studies have supported key information gaps on the health and economic benefits of intervening along the hepatitis B prevention and care cascade. These NEEMA studies found:
    • Revaccination of infants not responding to the prior vaccination series offered lower incremental cost per infant vaccinated when all 3 vaccination visits were assumed to occur during a scheduled well-child visit. Specifically, if all three vaccination visits occurred during a previously scheduled well-child visit, a single dose revaccination reduced the cost per individual by $28.29-$52.73 in 2016 USD depending on the scenario. Conversely, if all revaccination vaccine visits were previously unscheduled, the incremental decrease in cost per individual reached $119.81-$155.72 in 2016 USD.
    • Universal vaccination of all adults could avert nearly 24.8% of incident hepatitis B with a 3-dose series (24.6% in the 2-dose series) and 22.8% of hepatitis B related deaths in the 3-dose series (22.2% in 2-dose series) compared to current vaccination coverage. The cost per quality adjusted life year gained was similar if considering a 2-dose versus a 3-dose vaccination series ($152,722 for the 3-dose and $155,429 for the 2-dose vaccination series in 2019 USD).
    • Universal hepatitis B screening could be cost saving (assuming 0.24% prevalence of undiagnosed infections) for adults aged 18-69 years. Compared to current practice, universal HBsAg screening would save $262,857 in 2020 USD and would result in a gain of 135 quality adjusted life years per 100,000 adults screened.
  • As of January 2018, the Advisory Committee on Immunization Practices (ACIP) recommends the single-dose revaccination strategy for infants who are born to HBsAg-positive mothers and who do not respond to the initial hepatitis B vaccine series.
  • In November 2021, the ACIP issued a recommendation for universal vaccination of all adults against hepatitis B.

References

  1. Wong RJ, Brosgart CL, Welch S, et al. An updated assessment of chronic hepatitis B prevalence among foreign-born persons living in the United States. Hepatology 2021;74:607–26.
  2. Mark K. Weng, MD1; Mona Doshani, MD1; Mohammed A. Khan eet al., Hepatitis B Vaccination in Adults Aged 19–59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices —United States, 2022]. MMWR Morb Mortal Wkly Rep 2022;71/No.13 477-483.
  3. Hall EW, Rosenberg ES, Trigg M, Nelson N, Schillie S. Cost Analysis of Single-Dose Hepatitis B Revaccination Among Infants Born to Hepatitis B Surface Antigen-Positive Mothers and Not Responding to the Initial Vaccine Series. Public Health Rep. 2018 May/Jun;133(3):338-346. doi: 10.1177/0033354918768224. Epub 2018 Apr 17. PMID: 29664691; PMCID: PMC5958396.
  4. Hall EW, Weng MK, Harris AM, Schillie S, Nelson NP, Ortega-Sanchez IR, Rosenthal E, Sullivan PS, Lopman B, Jones J, Bradley H, Rosenberg ES. Assessing the cost-utility of universal hepatitis B vaccination among adults. J Infect Dis. 2022 Mar 9:jiac088. doi: 10.1093/infdis/jiac088. Epub ahead of print. PMID: 35260904.
  5. Toy M, Hutton D, Harris AM, Nelson N, Salomon JA, So S. Cost-Effectiveness of 1-Time Universal Screening for Chronic Hepatitis B Infection in Adults in the United States. Clin Infect Dis. 2022 Jan 29;74(2):210-217. doi: 10.1093/cid/ciab405. PMID: 33956937.
  6. Advisory Committee on Immunization Practices. Summary report: Revaccination for Unprotected Infants Born to HBsAg‐Positive Mothers. 3/1/2017. https://www.cdc.gov/vaccines/acip/meetings/downloads/min-archive/min-2017-02.pdf.
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Page last reviewed: June 14, 2022