Cost-Effectiveness of Adult Hepatitis A Vaccination Strategies in Korea Under an Aging Susceptibility Profile

Introduction to the show: ident: Genomics Radio. Generated commentary on the latest computational biology and genomics papers.

Ines: We're looking at the paper: "Cost-Effectiveness of Adult Hepatitis A Vaccination Strategies in Korea Under an Aging Susceptibility Profile".

Marcus: Here's the gist of the paper. The gist: Prioritizing adults aged 40–59 years offers the most balanced and robustly cost-effective strategy in Korea, capturing substantial mortality reduction while limiting additional program costs.

Ines: Hepatitis A severity increases sharply with age, while Korea is experiencing a cohort shift in which low-seroprevalence adult cohorts are aging into older, higher-fatality age groups This demographic and immunological transition creates an urgent policy question regarding how adult vaccination should be prioritized under resource constraints.

Marcus: In Korea, hepatitis A seroprevalence exhibits marked heterogeneity by age As of 2019, seroprevalence was lowest among individuals in their teens through their 40s, and a cohort shift is underway, whereby low-immunity cohorts are progressively aging into older groups This cohort-driven shift implies that future hepatitis A burden will increasingly concentrate in age groups with substantially higher fatality risk The study developed an age-structured transmission model calibrated to Korean agespecific epidemiological data and conducted a long-term, simulation-based cost-effectiveness analysis of adult hepatitis A vaccination strategies from both the healthcare system and societal perspectives The model stratifies the population into eight 10-year age groups It incorporates Korea’s National Immunization Program (NIP) to reflect real-world vaccination dynamics, including first-dose and second-dose vaccinations, as well as military recruits Three adult vaccination scenarios were evaluated: (S1) 20–39 years, (S2) 40–59 years with pre-vaccination antibody testing, and (S3) 20–59 years with antibody testing applied to those aged ≥40 years Optimal control theory was employed to derive monthly vaccination allocation trajectories for the period 2025-2054, minimizing a defined objective functional that includes disease burden and socioeconomic costs Disability-adjusted life years (DALYs) were computed using age-specific contributions to YLD and YLL over an evaluation horizon of 83 years, discounted at a continuous annual rate of 4.5% Key Findings on Vaccination Scenarios The analysis consistently showed that vaccination targeting adults aged 40–59 years (S2) yields the most favorable and robust cost-effectiveness profile under both perspectives, with the lowest ICER In terms of DALYs averted, vaccination of adults aged 20–59 years (S3) achieved the largest reduction but required substantially higher incremental costs compared to S2 Scenario S1 produced the smallest DALY reduction and was the least efficient strategy The optimal control strategies illustrated how vaccination effort would be preferentially allocated across age groups under each strategy to maximize health and socioeconomic benefits Specifically, in scenario S3, the optimal control strategy distributes doses almost evenly across adults in their 20s–50s from 2025 through the early 2040s Cost-Effectiveness and Uncertainty Analysis The incremental cost effectiveness ratio (ICER) was defined as Cost i - Cost base / DALY base - DALY i The results were consistent across both the healthcare system and societal perspectives, with S2 consistently emerging as the most efficient strategy In the healthcare system perspective, S2 yielded the lowest ICER (USD 52,166 per DALY averted), achieving a sizable reduction in DALYs (7,458 DALYs averted) with a moderate increase in costs The probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEACs) confirmed that S2 remains the preferred option across most willingness-to-pay ranges In the societal perspective, incremental costs for S2 and S3 are generally higher than those in the healthcare system perspective, reflecting the inclusion of additional cost components such as productivity losses and non-medical expenses Prioritizing adults aged 40–59 years offers the most balanced and robustly cost-effective strategy in Korea, capturing substantial mortality reduction while limiting additional program costs The relative advantage of S2 can be interpreted in terms of model dynamics, as allocating doses to adults closer to higher-fatality ages can avert substantially more deaths per dose than scenario focusing primarily on younger adults While broader vaccination of adults aged 20–59 years produced the largest absolute reductions in DALYs, these gains required substantially higher investment and were favored primarily at higher willingness-to-pay levels Therefore, under realistic capacity and budget constraints, prioritizing middle-aged adults provides the clearest value for money in Korea’s evolving epidemiological context Limitations Several limitations should be noted.

Ines: First, long-term projections depend on assumptions about future transmission intensity captured through the force of infection Second, vaccination implementation in reality may differ from model assumptions, as the study represented routine (non-outbreak) feasibility via a fixed monthly uptake constraint Third, we did not explicitly stratify high-risk subgroups with markedly elevated fatality These results underscore the importance of dynamic, context-specific economic evaluations for adult immunization policy in aging populations References 1.

Paper summary: Ines: So we're looking at this paper titled "Cost-Effectiveness of Adult Hepatitis A Vaccination Strategies in Korea Under an Aging Susceptibility Profile." Basically, the big question they're tackling is how we should prioritize adult vaccination when resources are limited.

Marcus: Yeah, and it focuses on the fact that hepatitis A gets much more severe as you get older. The paper claims there's a cohort shift happening in Korea where younger groups with low immunity are aging into older groups who have a much higher chance of death from the disease.

Yuki: That shift is key because it means future cases are going to hit those higher fatality age groups harder, so the policy question is really about where to put those limited preventive resources.

Ines: Exactly. The core thesis is that this demographic and immunological transition makes it urgent to figure out how adult vaccination should be prioritized under resource constraints. It sets up a real dilemma for public health planning.

Marcus: And they test three different scenarios: scenario one, targeting twenty to thirty-nine years old, scenario two, focusing on forty to fifty-nine years old with pre-vaccination antibody testing, and scenario three, which is the broadest at twenty to fifty-nine years old with antibody testing for those aged forty and older.

Yuki: The study uses an age structured dynamic transmission model that's calibrated specifically to Korean data. That means they are building a simulation that mirrors how the disease spreads in Korea right now based on what they know about the population.

Ines: They then use an optimal control framework within this model to figure out the best vaccination allocation trajectories, which is essentially deciding exactly when and where to give those doses to get the most benefit.

Marcus: The results are pretty telling because they link these vaccination strategies directly to long term transmission model simulations. This lets them see what happens over a long time horizon, not just right now.

Yuki: And they don't stop there; they conduct DALY based cost-effectiveness analyses from both the healthcare system and societal perspectives, which is important because it looks at the whole picture, not just medical costs.

Ines: They also characterized uncertainty using probabilistic sensitivity analysis and cost effectiveness acceptability curves, so we know how reliable those findings are across different willingness to pay levels.

Marcus: So what they found in the base case—which is scenario two—is that it consistently yields the most favorable and robust cost effectiveness profile under both perspectives, specifically with the lowest ICER.

Yuki: That means when you look at things like DALYs averted, scenario two gets a big chunk of those benefits while keeping the additional program costs relatively low compared to other options.

Ines: Scenario three did achieve the largest reduction in DALYs overall, but it required substantially higher incremental costs than scenario two, which ended up resulting in a higher ICER.

Paper summary: Marcus: Scenario one produced the smallest reduction in DALYs and was considered the least efficient strategy among the three options they tested.

Yuki: The probabilistic sensitivity analysis and cost effectiveness acceptability curves confirm that scenario two remains the preferred option across most willingness to pay ranges, which is a strong indicator of its real-world applicability.

Ines: It seems like scenario two offers the most balanced and robustly cost effective strategy in Korea right now, capturing substantial mortality reduction while keeping the additional program costs manageable.

Marcus: Scenario three might only be justified if you have higher budgets or if the willingness to pay thresholds you're willing to accept are significantly higher than what scenario two requires.

Yuki: It’s clear that under realistic capacity and budget constraints, scenario two provides the clearest value for money in Korea's current epidemiological context.

Ines: This whole paper on "Cost-Effectiveness of Adult Hepatitis A Vaccination Strategies in Korea Under an Aging Susceptibility Profile" really shows how important it is to look at age-specific risk when planning preventative medicine.

Marcus: It highlights that focusing resources on the middle-aged adults, specifically the forty to fifty-nine group, provides a strong return on investment in terms of both health outcomes and economic cost.

Yuki: It reinforces the idea that the shift in susceptibility profile isn't just a statistical detail; it’s driving a very real need for targeted intervention strategies.

Ines: So, what does this mean for us when we think about adult immunization policy globally? It suggests that we can't use one-size-fits-all approaches when dealing with diseases that have such strong age gradients in severity.

Marcus: It means the modeling approach used here, linking dynamic transmission to cost analysis, is a really useful way to test these kinds of complex allocation problems under real constraints.

Yuki: It supports the idea that understanding cohort shifts in immunity can fundamentally alter how we need to structure public health campaigns for things like hepatitis A.

Ines: And it shows that even when absolute reductions in DALYs are bigger, if the cost is too high, the strategy might not be practical for widespread implementation.

Marcus: So, when you think about these results from this paper, what's one thing you see as a major implication for how health systems should approach adult immunization programs?

Yuki: I see it as a call to action to move away from blanket recommendations and toward highly targeted strategies based on age-specific risk profiles.

Ines: It means we need better tools, like the dynamic models they built, so we can simulate these kinds of allocation decisions before we commit resources.

Marcus: And it emphasizes that the economic analysis needs to be done from multiple viewpoints—healthcare system versus societal costs—to get a truly balanced picture.

Yuki: It really underscores how crucial it is to keep track of cohort shifts, because ignoring them means you're planning for a disease profile that might not even exist in the future.

Conclusion: Ines: So this paper is looking at how to best vaccinate adults in Korea for Hepatitis A as people get older, focusing on cost versus benefit.

Marcus: Yeah, it's about finding the right strategy when you have limited resources because the disease gets more dangerous with age.

Yuki: From a population genetics standpoint, this cohort shift is really interesting because it tells us exactly which age groups are going to bear the brunt of the future burden.

Ines: The authors are testing three different vaccination scenarios—one for younger adults, one for middle-aged adults, and one that covers both—using a dynamic transmission model calibrated to Korean data.

Marcus: They use an optimal control framework within that model to figure out the best way to allocate doses over time, which is pretty technical.

Yuki: And they look at this through two lenses: the healthcare system's cost and the society's overall impact on life expectancy.

Ines: The main conclusion is that targeting adults aged forty to fifty-nine years presents the most balanced and robust strategy across both those views, with a lower cost-effectiveness ratio.

Marcus: That means scenario two wins because it cuts down on DALYs—disability-adjusted life years—while keeping the extra program costs reasonable.

Yuki: It suggests that for this specific disease in this specific country, focusing prevention efforts on that middle age group is the most sensible path forward right now.

Ines: They also use sensitivity analysis to check how reliable those results are across different willingness to pay levels, which gives you a sense of how practical the advice is.

Marcus: It’s a good check because it shows that scenario two stays the best choice even when you consider different economic viewpoints on what society is willing to spend.

Yuki: So, while broader vaccination might save more total life years, the cost gets so high that it’s not practical for widespread use.

Ines: Exactly. The paper suggests we need to be strategic about where we put those limited vaccination dollars in this evolving risk landscape.