Outcome of Infants Born to Women with Chronic Hepatitis B: A Local Risk-Based Strategy in a Low Prevalence Country.

BACKGROUND: Chronic hepatitis-B virus (HBV) infection due to mother-to-child transmission (MTCT) during the perinatal period is an important global health concern. Chile is a low-prevalence country with an increasing migratory inflow from Latin- American countries, with intermediate to high endemic rates of HBV infection, and until 2021, there is no universal maternal screening. This study aimed to evaluate infant outcomes using a risk-based strategy of maternal screening to prevent MTCT of hepatitis B virus (HBV) in a low-prevalence country. METHODS: This prospective study included infants born to HBsAg-positive women detected using a local risk-based strategy. The exposed infants received immunoprophylaxis (IP) and follow-up to evaluate their clinical outcomes and immune responses through post-serological vaccine testing (PSVT) after completing the three- dose schedule of the HBV vaccine. RESULTS: A total of 99 HBsAg-positive mothers were detected. Seventy-six (82%) infants completed the follow-up and had PSVT between 9 and 12 months of age. 55.2% female, the median gestational age was 39 weeks (25-41) and the median birth weight was 3,130g (816-4,400 g). All patients received IP with recombinant HBV vaccine plus hepatitis-B virus immunoglobulin (HBIG) and three doses of the HBV vaccine. There were no cases of HBV infection, and 96% (72) responded to immunization with HBsAg antibodies (anti-HBsAg) >10 UI/ml, with a median level of 799 IU/ml. CONCLUSIONS: A high-risk strategy can be implemented in countries with non-universal screening for VHB. Timely IP plus high-uptake VHB vaccination in infants born to HBsAg-positive mothers was associated with a high immunogenic response and absence of MTCT.

Impact of hepatitis B birth dose on immune response in Pakistani children: an open-label, non-inferiority randomized controlled trial, implications for achieving SDG target.

BACKGROUND: Despite presence of hyperendemic areas, the national immunisation schedule in Pakistan does not include a hepatitis B birth dose, placing newborns at an additional risk of acquiring hepatitis B. This study aimed to assess the impact of adding hepatitis B birth dose in existing national vaccination schedule. METHODS: An open label, randomised controlled non-inferiority trial enrolled 296 healthy near-term mothers to intervention and control groups. Newborns in the intervention group received a hepatitis B birth dose along with routine immunisation vaccines, while control group newborns received vaccinations under the national schedule. Seroprotection was measured and compared at birth and 8 weeks after administering the third dose of pentavalent vaccine. The risk ratio of seroprotection was computed and compared with the delta value set at 5%. RESULTS: The study found that 95.8% of infants in the intervention group achieved seroprotection, which was significantly higher than the control group's 58.7%. The difference in risk ratio of seroprotection was 1.62 (CI95: 1.37-1.93), with the upper limit of the CI below the delta margin, confirming non-inferiority. The time interval between birth and the first hepatitis B immunisation shot was a predictor of seroprotection, with an odds ratio of 1.79 (CI95: 1.01-2.9). CONCLUSION: Our study indicates that adding a hepatitis B birth dose to the immunisation schedule in Pakistan is non-inferior to the existing one. This can also contribute towards Pakistan's achievement of the SDG target of reducing hepatitis B surface antigen seroprevalence in children under 5 years of age. TRIAL REGISTRATION NUMBER: NCT04870021.

Fractional optimal control strategies for hepatitis B virus infection with cost-effectiveness analysis.

Hepatitis B disease is a communicable disease that is caused by the hepatitis B virus and has become a significant health problem in the world. It is a contagious disease that is transmittable from person to person either horizontally or vertically. This current study is aimed at sensitivity analysis and optimal control strategies for a fractional hepatitis B epidemic model with a saturated incidence rate in the sense of the Caputo order fractional derivative approach. Fundamental properties of the proposed fractional order model are obtained and discussed. A detailed analysis of disease-free equilibrium and endemic equilibrium points is given by applying fractional calculus theory, which is a generalized version of classical calculus. Sensitivity indexes are calculated for the classical order model. Illustrative graphics that show the dependence of the sensitivity index on fractional order derivative for [Formula: see text] are provided. Based on the results of the sensitivity analysis and using Pontryagin's Maximum Principle, optimal control strategies for preventing hepatitis B infection with vaccination and treatment are considered. Fractional Euler's method is used to carry out the numerical simulation for the proposed fractional optimal control system and the obtained results are analyzed. The results of the analysis reveal that hepatitis B disease can be prevented if necessary precautionary is taken or effective vaccination and treatment control measures are applied. The analysis of cost-effectiveness is also conducted and discussed.

Changes and gaps of global and regional disease burden of hepatitis B infection in children younger than 5 years old between 2015 and 2019: A real-world data review.

Hepatitis B virus (HBV) infection has been declared an ongoing health threat, especially infections among children. We compared and updated the disease burden of HBV infection and the effectiveness of vaccination among children younger than 5 years to offer indications for hepatitis B prevention across the world. The country-level data on the prevalence of hepatitis B surface antigen (HBsAg), the coverages of hepatitis B vaccine birth-dose (HepB-BD), three-dose series (HepB3), income level, population density/size, and human development index were collected from open access databases including WHO, UNICEF, and World Bank. Comparison of the prevalence of HBsAg under 5 years old between 2015 and 2019 based on vaccination coverages was conducted by the gamma generalized linear mixed model. Globally, more than 6.3 million HBV infections were estimated in children under 5 years in 2019, compared to 10.1 million in 2015 within the 179 countries involved. The pooled average prevalence of HBsAg among children younger than 5 years decreased from 1.4% (95% confidence interval [CI]: 1.1-1.8) to 0.9% (95% CI: 0.7-1.2). The rate difference or rate ratio was -0.5% (95% CI: -0.6% to -0.3%) or 0.51(95% CI: 0.44-0.58), respectively. Countries from the African region or with lower income/population density/human development indexes bore the most significant disease burden of hepatitis B. Higher coverages of hepatitis B vaccine birth-dose or primary series correlated with significant HBsAg prevalence decreases and much-decreased ratio, independently. Hepatitis B prevention among children under 5 years has significantly been achieved while remaining the most life-threatening disease burden, unequally distributed worldwide. The hepatitis B vaccination should be prioritized for all newborns, especially in those resource-constrained countries or regions.

Training the healthcare workforce to support task-shifting and viral hepatitis elimination: a global review of English language online trainings and in-person workshops for management of hepatitis B and C infection.

BACKGROUND: Achieving World Health Organization (WHO) targets for viral hepatitis elimination will require simplification and decentralisation of care, supported through task-shifting and training of non-specialist frontline healthcare workers. To inform development of national health worker trainings in viral hepatitis, we review and summarise available online and workshop trainings for management of hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: We performed a systematic search of PubMed, Embase, Web of Science, conference abstracts, and grey literature using Google to identify online and in-person workshop trainings for health workers focused on HBV and/or HCV. Additional trainings were identified through a WHO regional network. We included online trainings written in English and in-person workshops developed for low-and-middle-income countries (LMICs). Available curricula are summarised together with key operational features (e.g. training length, year developed/updated, developing institution) and programmatic features (e.g. content, mechanism for self-assessment, use of clinical case studies). RESULTS: A total of 30 trainings met our inclusion criteria (10 online trainings; 20 in-person workshops). 50% covered both HBV and HCV, 13% HBV alone and 37% HCV alone. Among online trainings, only 2 (20%) were specifically developed or adapted for LMICs; 70% covered all aspects of hepatitis care, including prevention, assessment, and treatment; 9 (90%) included guidance on when to refer to specialists, and 6 (60%) included modules on management in specific populations (e.g., people who inject drugs [PWID], prisoners, and children). Online trainings used different formats including text-based modules, narrated slide-sets, and interactive web-based modules. Most workshops (95%) were targeted towards non-specialty providers, and 50% were an integral part of a national strategy for viral hepatitis elimination. Workshop length ranged from several hours to multiple sessions over the course of months, and many were part of a blended educational model, which included other opportunities for ongoing learning (e.g., telementorship). CONCLUSION: This compendium of online and in-person workshop trainings for HBV and HCV is a useful resource for national hepatitis programmes developing training curricula for non-specialists. Additional online training curricula are needed for use in LMICs, and additional materials are needed to address management challenges in key populations, such as PWID.

A global investment case for hepatitis B elimination: a modelling study.

Hepatitis B is estimated to cause 500 000-900 000 deaths globally each year. WHO has targets for elimination by 2030; however, progress has stalled due to multiple barriers, notably a paucity of global funding and insufficient evidence on the economic burden of disease. Using a dynamic mathematical model of hepatitis B transmission, disease progression, and mortality in the six WHO regions, we estimate the costs and benefits of reaching 90% vaccination, 90% diagnosis, and 80% treatment coverage by either 2030 (as targeted), 2040, or 2050. Without increased intervention coverage, hepatitis B mortality was estimated to cost US$784·35 billion (95% Crl 731·63-798·33 billion) globally in lost productivity over 2022-50. Achieving targets by 2030 averted 25·64 million infections (95% Crl 17·39-34·55 million) and 8·63 million hepatitis B-attributable deaths (95% Crl 7·12-9·74 million) over 2022-50. This achievement incurred an incremental cost of $2934·55 (95% Crl 2778·55-3173·52) per disability-adjusted life year averted by 2050 under a health systems perspective, and was cost-saving with a net economic benefit of $99·03 billion (95% Crl 78·66-108·96 billion) by 2050 from a societal perspective. Delayed achievement of intervention coverage targets had reduced health and economic benefits. These findings highlight that hepatitis B is an underappreciated cause of economic burden and show investment toward elimination will probably yield substantial returns.

Impact and Cost-Effectiveness of Biomedical Interventions on Adult Hepatitis B Elimination in China: A Mathematical Modelling Study.

BACKGROUND: China has one of the highest hepatitis B virus (HBV) disease burdens worldwide and tracking progress toward the 2030 HBV elimination targets is essential. This study aimed to assess the impact of biomedical interventions (i.e., adult vaccination, screening and treatment) on the adult HBV epidemic, estimate the time for HBV elimination, and evaluate the cost-effectiveness of the interventions in China. METHODS: A deterministic compartmental model was developed to project the HBV epidemic from 2022 to 2050 and estimate the time to meet elimination targets under four intervention scenarios. Cost-effectiveness was calculated using incremental cost per quality-adjusted life year (QALY) gained, i.e., average cost-effectiveness ratio (CER). RESULTS: Under the status quo, there will be 42.09-45.42 million adults living with HBV in 2050 and 11.04-14.36 million HBV-related deaths cumulatively from 2022 to 2050. Universal vaccination would cumulatively avert 3.44-3.95 million new cases at a cost of US$1027-1261/QALY gained. The comprehensive strategy would cumulatively avert 4.67-5.24 million new chronic cases and 1.39-1.85 million deaths, expediting the realization of the elimination targets forward to 2049. This strategy was also cost-effective with an average CER of US$20,796-26,685/QALY and a saved healthcare cost of US$16.10-26.84 per person. CONCLUSION: China is not on track to meet the elimination targets but comprehensive biomedical interventions can accelerate the realization of the targets. A comprehensive strategy is cost-effective and cost-saving, which should be promoted in primary care infrastructures. Universal adult vaccination may be appropriate in the near future considering practical feasibility.

Impact and cost-effectiveness of hepatitis B virus prophylaxis in pregnancy: a dynamic simulation modelling study.

BACKGROUND: In 2020, WHO recommended the addition of peripartum antiviral prophylaxis (PAP) to hepatitis B birth dose vaccination (HepB-BD) and hepatitis B infant vaccination (HepB3) to reduce mother-to-child transmission of hepatitis B virus (HBV) infection in pregnant women who have a marker of high infectivity (ie, HBV DNA ≥200 000 international units per mL or HBeAg-positive). We aimed to evaluate the impact and cost-effectiveness of this recommendation and of a theoretical simplified strategy whereby PAP is given to all pregnant women who are HBsAg-positive without risk stratification. METHODS: This modelling study used a dynamic simulation model of the HBV epidemic in 110 countries in all WHO regions, structured by age, sex, and country. We assessed three strategies of scaling up PAP for pregnant women: PAP for those with high viral load (PAP-VL); PAP for those who are HBeAg-positive (PAP-HBeAg); and PAP for all pregnant women who are HBsAg-positive (PAP-universal), in comparison with neonatal vaccination alone (HepB-BD). We investigated how different diagnostic and antiviral drug costs affected the cost-effectiveness of the strategies evaluated. Using a health-care provider perspective, we calculated incremental cost-effectiveness ratios in cost (US$) per disability-adjusted life-year (DALY) averted in each country's population and compared these with country-specific cost-effectiveness thresholds. We also calculated new neonatal infections averted for each of the strategies. FINDINGS: Adding PAP-VL to HepB-BD could avert around 1·1 million (95% uncertainty interval 1·0 million-1·2 million) new neonatal infections by 2030 and around 3·2 million (95% uncertainty interval 3·0 million-3·4 million) new neonatal infections and approximately 8·8 million (7·8 million-9·7 million) DALYs by 2100 across all the countries modelled. This strategy would probably be cost-effective up to 2100 in 28 (26%) of 106 countries analysed (which included some of the countries that have the greatest HBV burden) if costs are as currently expected to be, and in 74 (70%) countries if diagnostic and monitoring costs were lowered (by about 60-75%). The relative cost-effectiveness of PAP-VL and PAP-HBeAg was finely balanced and depended on the respective diagnostic and monitoring costs. The PAP-universal strategy could be more cost-effective than either of these strategies in most countries, but the use of antiviral treatment could be five times as high than with PAP-VL. INTERPRETATION: PAP can provide substantial health benefits, and, although the current approach might already be cost-effective in some high-burden settings, decreased diagnostic costs would probably be needed for PAP to be cost-effective in most countries. Therefore, careful consideration needs to be given about how such a strategy is implemented, and securing reduced costs for diagnostics should be a priority. The theoretical strategy of offering PAP to all women who are HBsAg-positive (eg, if diagnostic tests to identify mothers at risk of transmission are not available) could be a cost-effective alternative, depending on prevailing costs of diagnostics and antiviral therapy. FUNDING: UK Medical Research Council, UK National Institute for Health and Care Research, and the Vaccine Impact Modelling Consortium.

Knowledge, attitudes and practices of undergraduate health sciences students on hepatitis B vaccination at a South African university highlight the need for improvement of policies, implementation and co-ordination.

BACKGROUND: Hepatitis B virus (HBV) infection causes nearly 300 million chronic infections globally. Healthcare workers face up to four times the risk of HBV infection through occupational exposure to contaminated blood and bodily fluids. Health sciences students (HSSs) are regarded as at an even greater risk as they embark on their clinical training journey. While chronic hepatitis B is incurable, it can be prevented by the safe and effective hepatitis B vaccine (HepB). The South African National Department of Health recommends at least three doses of vaccine (HepB3) for HSSs before patient contact. However, data on policy implementation at training institutions, vaccine coverage and HBV immunity in HSSs are lacking or limited. OBJECTIVES: To investigate knowledge, attitudes and practices of HSSs at the University of the Witwatersrand (Wits) in relation to international guidelines and institutional HepB programmes included in the Wits vaccination policy. Sociodemographic factors predicting HepB uptake were also investigated. METHODS: A cross-sectional study was conducted between February and June 2021. An electronic, self-administered survey was emailed to all current HSSs (N=3 785). The survey included questions on sociodemographic characteristics, knowledge of and attitudes towards HepB- related international guidelines and Wits policies, and HepB uptake and vaccine practices at Wits. Descriptive statistical analyses, followed by multivariable regression modelling, were used to identify factors associated with HepB uptake. RESULTS: A response rate of only 7.1% yielded 269 returned surveys, of which 221 were adequate for analysis. Most respondents were female (69.2%), with a mean (standard deviation) age of 22.5 (3.5) years, and were studying a Bachelor of Medicine and Surgery (MB BCh) degree (76.9%). Only 78% of those students who reported a history of vaccination (89.1% of study sample) reported a completed vaccine series. The only significant predictor, when adjusted for interactions, was being enrolled in MB BCh compared with other courses (odds ratio 4.69; p=0.026). Students displayed higher levels of knowledge around institutional (Wits) vaccine recommendations (94.1%) compared with international recommendations (75.6%). Most students were in favour of mandatory vaccination (91.4%), but not of serological testing following vaccination (42.5%). Half of our students received vaccinations in private facilities, but no follow-up or record was made of this by the designated Wits Campus Health and Wellness Centre. CONCLUSION: Institutional HepB policies are suboptimal, with no centralised co-ordination or implementation strategy. Urgent efforts are required to create awareness around policy and management, ensure vaccination coverage in this high-risk group, and foster positive practices with adequate monitoring.

Cost-effectiveness of a 3-antigen versus single-antigen vaccine for the prevention of hepatitis B in adults in the United States.

OBJECTIVES: The first 3-antigen hepatitis B vaccine was approved by the United States (US) Food and Drug Administration in November 2021 and was recommended by the Centers for Disease Control and Prevention in 2022. We estimated the cost-effectiveness of this 3-antigen vaccine (PreHevbrio™) relative to the single-antigen vaccine, Engerix-BTM, to prevent hepatitis B virus (HBV) infection among US adults. METHODS: A cost-effectiveness model was developed using a combined decision-tree and Markov structure to follow 100,000 adults over their remaining lifetimes after vaccination with either the 3-antigen or single-antigen vaccine. Outcomes from societal and healthcare sector perspectives were calculated for adults aged 18-44, 45-64, and ≥65 years; adults with diabetes; and adults with obesity. Seroprotection rates were obtained from the phase3, head-to-head PROTECT trial (NCT03393754). Incidence, vaccine costs, vaccine adherence rates, direct and indirect costs, utilities, transition probabilities, and mortality were obtained from published sources. Health outcomes and costs (2020USD) were discounted 3% annually and reported by vaccine and population. One-way sensitivity and scenario analyses were conducted. RESULTS: In the model, the 3-antigen vaccine led to fewer HBV infections, complications, and deaths compared with the single-antigen vaccine in all modeled populations due to higher rates and faster onset of seroprotection. Compared with the single-antigen vaccine, the 3-antigen vaccine had better health outcomes, more quality-adjusted life-years (QALYs), and lower costs in adults aged 18-64 years, adults with diabetes, and adults with obesity (dominant strategy). For adults aged ≥65 years, the 3-antigen vaccine was cost-effective compared with the single-antigen vaccine ($26,237/QALY gained) below common willingness-to-pay thresholds ($50,000-$100,000/QALY gained). In sensitivity analyses, results were sensitive to vaccine cost per dose, incidence, and age at vaccination. CONCLUSION: The recently approved 3-antigen vaccine is a cost-saving or cost-effective intervention for preventing HBV infection and addressing the long-standing burden of hepatitis B among US adults.

An Intersectional Approach to Hepatitis B.

Hepatitis B is a chronic condition, primarily associated with hepatitis B viral infection in early life. The failure of prevention and appropriate management can lead to subsequent liver cirrhosis and cancer. Hepatitis B most commonly affects people born in Asia and Sub-Saharan Africa and their global diasporas. The physical, psychological, and social impacts of hepatitis B are strongly influenced by sex and gender. Inequities in access to timely, sensitive diagnosis and effective management arise from interactions between structural inequalities related to race, ethnicity, Indigenous/settler status, class, and geography. The biomedical response to hepatitis B has led to advances in prevention, diagnosis, and treatment, but many affected communities have explanatory health belief models that differ from that of biomedicine. We argue that an intersectional approach, led by affected people and communities, can integrate biomedicine with the lived experience and social context that give purpose to and shape all personal, communal, clinical, and public health responses to hepatitis B. This approach has the potential to enable a consciously equitable, effective response to the biopsychosocial complexities of hepatitis B, improve the health and wellbeing of people living with hepatitis B, and reduce hepatitis B-associated mortality.

Economic Impact of European Liver and Intestine Transplantation Association (ELITA) Recommendations for Hepatitis B Prophylaxis After Liver Transplantation.

The European Liver and Intestine Transplant Association, ELITA, promoted a Consensus Conference involving 20 experts across the world which generated updated guidelines on HBV prophylaxis in liver transplant candidates and recipients. This study explores the economic impact associated with the implementation of the new ELITA guidelines. To this aim, a condition-specific cohort simulation model has been developed to compare new and historical prophylaxis, including only pharmaceutical cost and using the European perspective. The target population simulated in the model included both prevalent and incident cases, and consisted of 6,133 patients after the first year, that increased to 7,442 and 8,743 patents after 5 and 10 years from its implementation. The ELITA protocols allowed a cost saving of around € 235.65 million after 5 years and € 540.73 million after 10 years; which was mainly due to early HIBG withdrawal either after the first 4 weeks or after the first year post Liver Transplantation (LT) depending on the virological risk at transplantation. Results were confirmed by sensitivity analyses. The money saved by the implementation of the ELITA guidelines would allow healthcare decision makers and budget holders to understand where costs could be reduced and resources re-allocated to different needs.

The cost-effectiveness of universal hepatitis B screening for reaching WHO diagnosis targets in Australia by 2030.

OBJECTIVES: To assess the impact on diagnosis targets, cost, and cost-effectiveness of universal hepatitis B screening in Australia. DESIGN: Markov model simulation of disease and care cascade progression for people with chronic hepatitis B in Australia. SETTING: Three scenarios were compared: 1. no change to current hepatitis B virus (HBV) testing practice; 2. universal screening strategy, with the aim of achieving the WHO diagnosis target by 2030 (90% of people with chronic hepatitis B diagnosed), based on opportunistic (general practitioner-initiated) screening for HBsAg; 3. universal screening strategy, and also ensuring that 50% of people with chronic hepatitis B are receiving appropriate clinical management by 2030. MAIN OUTCOME MEASURES: Projected care cascade for people with chronic hepatitis B, cumulative number of HBV-related deaths, intervention costs, and health utility (quality-adjusted life-years [QALYs] gained during 2020-2030). An incremental cost-effectiveness ratio (ICER) threshold (v scenario 1) of $50 000 per QALY gained was applied. RESULTS: Compared with scenario 1, 80 HBV-related deaths (interquartile range [IQR], 41-127 deaths) were averted during 2020-2030 in scenario 2, 315 HBV-related deaths (IQR, 211-454 deaths) in scenario 3. Scenario 2 cost $84 million (IQR, $41-106 million) more than scenario 1 during 2020-2030 (+8%), yielding an ICER of $104 921 (IQR, $49 587-107 952) per QALY gained. Scenario 3 cost $263 million (IQR, $214-316 million) more than scenario 1 during 2020-2030 (+24%), yielding an ICER of $47 341 (IQR, $32 643-58 200) per QALY gained. Scenario 3 remained cost-effective if the test positivity rate was higher than 0.35% or the additional costs per person tested did not exceed $4.02. CONCLUSIONS: Universal screening for hepatitis B will be cost-effective only if the cost of testing is kept low and people receive appropriate clinical management.

Cost-effectiveness modelling of birth and infant dose vaccination against hepatitis B virus in Ontario from 2020 to 2050.

BACKGROUND: The World Health Organization recommends universal birth dose vaccination for hepatitis B virus (HBV), yet only 3 provinces and territories in Canada provide birth dose vaccination, and Canadian-born children in Ontario are acquiring HBV before adolescent vaccination. We sought to determine whether birth and/or infant HBV vaccination is cost-effective. METHODS: We used a dynamic HBV model that incorporates population by year, disease stage, sex and the influence of immigration to quantify the disease and economic burden of chronic HBV infection in Ontario from 2020 to 2050. We compared 4 vaccination scenarios, which included a birth dose vaccine and variations of the 2 subsequent doses (either alone or as a part of the hexavalent vaccine) and a hexavalent-only strategy in infancy with the current adolescent vaccination strategy. Our costing estimates were based on values from 2020. RESULTS: All 4 infant vaccination approaches prevented an additional 550-560 acute and 160 chronic pediatric HBV infections from 2020 to 2050 compared with adolescent vaccination. Whereas birth dose could be cost-effective, incorporating vaccination into a hexavalent vaccine was cost saving. By 2050, the hexavalent approach led to $428 000 in cost savings per disability-adjusted life years averted. INTERPRETATION: At the current prevalence in Ontario, a switch to birth dose or infant dose will be cost-effective or even cost saving. Introducing any form of infant HBV immunization in Ontario will prevent acute and chronic pediatric HBV infections.

Cost Effectiveness of Implementing a Universal Birth Hepatitis B Vaccination Program in Ontario.

BACKGROUND AND OBJECTIVE: The World Health Organization recommends a universal hepatitis B vaccination within the first 24 h of birth. However, hepatitis B vaccines are given during adolescence in many jurisdictions including in Ontario, Canada. The objective of this study was to assess the cost effectiveness of shifting the hepatitis B vaccination timing from adolescence to birth. METHODS: A state-transition model of 18 health states representing the natural history of acute and chronic hepatitis B was developed to conduct a cost-utility analysis. Most input parameters were obtained from the Canadian literature or publicly available provincial data. The model followed a lifetime model time horizon with health outcomes and costs being discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model. Analyses were conducted from a public-payer perspective with all costs adjusted to 2021 Canadian dollars. RESULTS: Hepatitis B vaccination in newborns dominated the current strategy of adolescent vaccination. The probabilistic analysis showed that the newborn strategy was cost effective in 100% of the iterations at a willingness-to-pay threshold of $50,000/quality-adjusted life-year and cost saving in 79.39% of the iterations. A microsimulation projected that a newborn vaccination may lead to reductions in cases by 16.1% in acute hepatitis B, 43.2% in chronic hepatitis B, 48.2% in hepatocellular carcinoma, and 51.9% in hepatitis B liver-related death. CONCLUSIONS: Our analysis suggests that changing the age of the hepatitis B vaccination recommendation from adolescent to newborn is cost effective and mostly a cost-saving strategy. Newborn vaccination may lead to cost and health benefits while aligning with best available evidence and guidance from the World Health Organization.

The First 30 Years of the Universal Hepatitis-B Vaccination-Program in Italy: A Health Strategy with a Relevant and Favorable Economic-Profile.

In 1991, Italy was one of the first countries worldwide to introduce a universal hepatitis-B vaccination for children. Since then, epidemiological data have clearly demonstrated the huge clinical benefits of the vaccination. The aim of this study was to update the favorable economic impact of the hepatitis B virus (HBV) vaccination, 30 years after its implementation. A mathematical model was developed to simulate the clinical/economic impact of the universal HBV-vaccination program versus a hypothetical no-vaccination scenario as a posteriori analysis. We assessed the vaccination benefits over a 30-year-immunization-period (1991−2020), and the following period, 2021−2070. Our data showed a big drop in HBV-related diseases (−82% in infections, chronic disease, and hepatocellular-carcinoma cases), and related costs (−67% in the immunization period and −85% in 2021−2070), attributable to vaccination. The return on investment (ROI) and the benefit-to-cost (BCR) ratios are >1 for the first thirty-year-immunization-period, and are predicted to almost triplicate the economic savings in the period 2021−2070, both for the National Health Service (NHS) and from societal perspectives. Our model confirmed that the implementation of universal HBV-vaccination in Italy during the first 30 years continues to be a cost-saving strategy, and more advantageous effects will be further achieved in the future. The HBV-vaccination strategy greatly expresses a huge impact in both the short- and long-term, and from the clinical and economic point-of-views.

Evaluation of the health promotion effect of hepatitis B prevention and treatment in the Zhejiang demonstration area, China.

BACKGROUND: To investigate the health literacy level and health promotion effect of hepatitis B prevention and treatment in the demonstration area of Zhejiang Province. METHODS: The National Science and Technology Major Health Education Group took 6 demonstration areas in Zhejiang Province as the whole research site. After the sample size (N=2160 people) was determined, a multistage stratified cluster sampling method was used to conduct a questionnaire survey in 2018 (before health education) and 2019 (after health education). Stata 12 statistical software was used to analyse the status and improvement rate of hepatitis B health literacy of residents in the demonstration area before and after health education and compare the health promotion effects of different health intervention methods. RESULTS: Before and after health education, there was no significant difference in the basic information of the subjects (P>0.05). After the health education intervention, the level of hepatitis B health literacy of residents in the demonstration area increased by 11.8%, and the difference was statistically significant (P < 0.001). The awareness rate of hepatitis B transmission was low before health education but increased after health education. The form of "Internet +" health education may better improve the residents' health literacy level about hepatitis B prevention and treatment. CONCLUSION: After health education, the level of health literacy of residents in the Zhejiang demonstration area about hepatitis B prevention and control significantly improved, but there is room for further improvement. In the future, targeted health education intervention should be carried out, and the health education mode of "Internet +" can achieve better results to effectively prevent and control hepatitis B.

Impact of the national hepatitis B immunization program in China: a modeling study.

BACKGROUND: Elimination of hepatitis B virus (HBV) is a striking challenge for countries with high or moderate disease burden. Therefore, using China as a practical case to share experiences for similar countries may accelerate the achievement of the WHO 2030 target of 90% reduction in HBV-related incidence. We aim to evaluate the impact of national HBV immunization strategies in China; and the feasibility to achieve WHO 2030 targets under different scenarios. METHODS: We constructed an expanded Susceptible-Exposed-Infectious-Recovered (SEIR) model and decision tree-Markov model to estimate the epidemic of HBV in China, assess the feasibility of 2030 Elimination Goals through the projections and conduct the economic analysis. Least square method was used to calibrate the expanded SEIR model by yearly data of laboratory-confirmed HBV cases from 1990 to 2018. Two models were separately used to evaluate the impact and cost-effectiveness of HBV vaccine by comparing prevalence of chronic HBV infections, quality-adjusted life-years (QALYs), incremental cost effectiveness ratio and benefit-cost ratio (BCR) under various intervention options, providing a basis for exploring new containment strategies. RESULTS: Between 1990 and 2020, the number of chronic HBV infections decreased by 33.9%. The current status quo would lead to 55.73 million infections (3.95% prevalence) in 2030, compared to 90.63 million (6.42% prevalence) of the "Without the NIP" scenario (NIP: National Immunization Program), 114.78 million (8.13% prevalence) without any interventions. The prevention of mother to child transmission (PMTCT) strategy showed a net benefit as 12,283.50 dollars per person, with BCR as 12.66, which is higher than that of universal vaccination at 9.49. Compared with no screening and no vaccination, the PMTCT strategy could save 7726.03 dollars for each QALY increase. CONCLUSIONS: Our findings proved the HBV vaccination has demonstrated a substantial positive impact on controlling the epidemic of HBV in terms of effectiveness and economy after about 30 years of implementation of the national hepatitis B immunization program which also provided containment experience for high or medium burden countries. As for China, the next step should focus on exploring strategies to improve diagnosis and treatment coverage to reduce the burden of HBV-related deaths and ultimately eliminate HBV.