The case for a universal hepatitis C vaccine to achieve hepatitis C elimination.

BACKGROUND: The introduction of highly effective direct-acting antiviral (DAA) therapy for hepatitis C has led to calls to eliminate it as a public health threat through treatment-as-prevention. Recent studies suggest it is possible to develop a vaccine to prevent hepatitis C. Using a mathematical model, we examined the potential impact of a hepatitis C vaccine on the feasibility and cost of achieving the global WHO elimination target of an 80% reduction in incidence by 2030 in the era of DAA treatment. METHODS: The model was calibrated to 167 countries and included two population groups (people who inject drugs (PWID) and the general community), features of the care cascade, and the coverage of health systems to deliver services. Projections were made for 2018-2030. RESULTS: The optimal incidence reduction strategy was to implement test and treat programmes among PWID, and in settings with high levels of community transmission undertake screening and treatment of the general population. With a vaccine available, the optimal strategy was to include vaccination within test and treat programmes, in addition to vaccinating adolescents in settings with high levels of community transmission. Of the 167 countries modelled, between 0 and 48 could achieve an 80% reduction in incidence without a vaccine. This increased to 15-113 countries if a 75% efficacious vaccine with a 10-year duration of protection were available. If a vaccination course cost US$200, vaccine use reduced the cost of elimination for 66 countries (40%) by an aggregate of US$7.4 (US$6.6-8.2) billion. For a US$50 per course vaccine, this increased to a US$9.8 (US$8.7-10.8) billion cost reduction across 78 countries (47%). CONCLUSIONS: These findings strongly support the case for hepatitis C vaccine development as an urgent public health need, to ensure hepatitis C elimination is achievable and at substantially reduced costs for a majority of countries.

Cost-effective options for the prevention and management of gastrointestinal and liver disease in the Asia-Pacific region.

The Asia-Pacific region contains more than half of the world's population and is markedly heterogeneous in relation to income levels and the provision of public and private health services. For low-income countries, the major health priorities are child and maternal health. In contrast, priorities for high-income countries include vascular disease, cancer, diabetes, dementia, and mental health disorders as well as chronic inflammatory disorders such as hepatitis B and hepatitis C. Cost-effectiveness analyses are methods for assessing the gains in health relative to the costs of different health interventions. Methods for measuring health outcomes include years of life saved (or lost), quality-adjusted life years, and disability-adjusted life years. The incremental cost-effectiveness ratio measures the cost (usually in US dollars) per life year saved, quality-adjusted life year gained, or disability-adjusted life year averted of one intervention relative to another. In low-income countries, approximately 50% of infant deaths (< 5 years) are caused by gastroenteritis, the major pathogen being rotavirus infection. Rotavirus vaccines appear to be cost-effective but, thus far, have not been widely adopted. In contrast, infant vaccination for hepatitis B is promoted in most countries with a striking reduction in the prevalence of infection in vaccinated individuals. Cost-effectiveness analyses have also been applied to newer and more expensive drugs for hepatitis B and C and to government-sponsored programs for the early detection of hepatocellular, gastric, and colorectal cancer. Most of these studies reveal that newer drugs and surveillance programs for cancer are only marginally cost-effective in the setting of a high-income country.

Strategies for the prevention of perinatal hepatitis B transmission in a marginalized population on the Thailand-Myanmar border: a cost-effectiveness analysis.

BACKGROUND: Data on the cost effectiveness of hepatitis B virus (HBV) screening and vaccination strategies for prevention of vertical transmission of HBV in resource limited settings is sparse. METHODS: A decision tree model of HBV prevention strategies utilised data from a cohort of 7071 pregnant women on the Thailand-Myanmar border using a provider perspective. All options included universal HBV vaccination for newborns in three strategies: (1) universal vaccination alone; (2) universal vaccination with screening of women during antenatal visits with rapid diagnostic test (RDT) plus HBV immune globulin (HBIG) administration to newborns of HBV surface antigen positive women; and (3) universal vaccination with screening of women during antenatal visits plus HBIG administration to newborns of women testing HBV e antigen positive by confirmatory test. At the time of the study, the HBIG after confirmatory test strategy was used. The costs in United States Dollars (US$), infections averted and incremental cost effectiveness ratios (ICERs) were calculated and sensitivity analyses were conducted. A willingness to pay threshold of US$1200 was used. RESULTS: The universal HBV vaccination was the least costly option at US$4.33 per woman attending the clinic. The HBIG after (RDT) strategy had an ICER of US$716.78 per infection averted. The HBIG after confirmatory test strategy was not cost-effective due to extended dominance. The one-way sensitivity analysis showed that while the transmission parameters and cost of HBIG had the biggest impact on outcomes, the HBIG after confirmatory test only became a cost-effective option when a low test cost was used or a high HBIG cost was used. The probabilistic sensitivity analysis showed that HBIG after RDT had an 87% likelihood of being cost-effective as compared to vaccination only at a willingness to pay threshold of US$1200. CONCLUSIONS: HBIG following confirmatory test is not a cost-effective strategy for preventing vertical transmission of HBV in the Thailand-Myanmar border population. By switching to HBIG following rapid diagnostic test, perinatal infections will be reduced by nearly one third. This strategy may be applicable to similar settings for marginalized populations where the confirmatory test is not logistically possible.

Cost-effectiveness analysis of vaccinations and decision makings on vaccination programmes in Hong Kong: A systematic review.

OBJECTIVES: To describe and systematically review the modelling and reporting of cost-effectiveness analysis of vaccination in Hong Kong, and to identify areas for quality enhancement in future cost-effectiveness analyses. METHODS: We conducted a comprehensive and systematic review of cost-effectiveness studies related to vaccination and government immunisation programmes in Hong Kong published from 1990 to 2015, through database search of Pubmed, Web of Science, Embase, and OVID Medline. Methodological quality of selected studies was assessed using Consolidated Health Economic Evaluation Reporting Standards checklist (CHEERS). Decision making of vaccination was obtained from Scientific Committee on Vaccine Preventable Diseases (SCVPD) and Department of Health in Hong Kong. RESULTS: Nine eligible studies reporting twelve comparative cost-effectiveness comparisons of vaccination programme for influenza (n=2), pneumococcal disease (n=3), influenza plus pneumococcal disease (n=1), chickenpox (n=2), Haemophilus influenzae b (n=1), hepatitis A (n=1), cervical cancer (n=1) and rotavirus (n=1) were identified. Ten comparisons (83.3%) calculated the incremental cost-effectiveness ratio (ICER) of a vaccination strategy versus status quo as outcomes in terms of cost in USD per life-years, cost per quality-adjusted life-years, or cost per disability-adjusted life-years. Among those 10 comparisons in base-case scenario, 4 evaluated interventions were cost-saving relative to status quo while the ICER estimates in 3 of the 6 remaining comparisons were far below commonly accepted threshold and WHO willingness-to-pay threshold, suggestive of very cost-effective. Seven studies were of good quality based on the CHEERS checklist; one was of moderate quality; and one was of excellent quality. The common methodological problems were characterisation of heterogeneity and reporting of study parameters. CONCLUSIONS: There was a paucity of cost-effectiveness models evaluating vaccination targeted to the Hong Kong population. All evaluated vaccinations and immunisation interventions in Hong Kong, except for Haemophilus influenzae b, hepatitis A and HPV vaccinations, were considered either cost-saving or very cost-effective when compared to status quo.

Health economic evaluation of immunization strategies of hepatitis E vaccine for elderly population.

Objective This study was conducted to assess the cost-effectiveness of hepatitis E vaccination of elderly population in the sporadic regions in China. Methods We used a decision tree-Markov model to evaluate the cost-effectiveness of 3 kinds of hepatitis E virus vaccination strategies from societal perspectives. Parameter estimates were obtained from published researches and experts' opinion. The time horizon was 16 years, and the discounted rate was 3% annually. Costs are expressed in 2016 US dollars. Results The universal vaccination strategy had an incremental cost-effectiveness ratio (ICER) of US$ 8475.90 per QALY gained versus no vaccination. The implementation of screening and vaccination strategy would have an ICER of US$ 4044.28, compared with no vaccination. The vaccination was cost-effective (ICER< 3 times China's per capital gross domestic product/quality-adjusted life years). The QALY of asymptomatic infection, vaccine coverage and vaccine protection are the important parameters impacting the ICER in one-way sensitivity analysis and screening and vaccination being the dominant strategy in probabilistic sensitivity analysis. Conclusion This analysis indicates that screening and vaccination is the most cost-effective hepatitis E intervention strategy of elderly population in sporadic region in China.

[Use the Markov-decision tree model to optimize vaccination strategies of hepatitis E among women aged 15 to 49].

Objective: To evaluate the cost-utility of different hepatitis E vaccination strategies in women aged 15 to 49. Methods: The Markov-decision tree model was constructed to evaluate the cost-utility of three hepatitis E virus vaccination strategies. Parameters of the models were estimated on the basis of published studies and experience of experts. Both methods on sensitivity and threshold analysis were used to evaluate the uncertainties of the model. Results: Compared with non-vaccination group, strategy on post-screening vaccination with rate as 100%, could save 0.10 quality-adjusted life years per capital in the women from the societal perspectives. After implementation of screening program and with the vaccination rate reaching 100%, the incremental cost utility ratio (ICUR) of vaccination appeared as 5 651.89 and 6 385.33 Yuan/QALY, respectively. Vaccination post to the implementation of a screening program, the result showed better benefit than the vaccination rate of 100%. Results from the sensitivity analysis showed that both the cost of hepatitis E vaccine and the inoculation compliance rate presented significant effects. If the cost were lower than 191.56 Yuan (RMB) or the inoculation compliance rate lower than 0.23, the vaccination rate of 100% strategy was better than the post-screening vaccination strategy, otherwise the post-screening vaccination strategy appeared the optimal strategy. Conclusion: Post-screening vaccination for women aged 15 to 49 from social perspectives seemed the optimal one but it had to depend on the change of vaccine cost and the rate of inoculation compliance.

The Potential Impact of a Hepatitis C Vaccine for People Who Inject Drugs: Is a Vaccine Needed in the Age of Direct-Acting Antivirals?

BACKGROUND AND AIMS: The advent of highly effective hepatitis C (HCV) treatments has questioned the need for a vaccine to control HCV amongst people who inject drugs (PWID). However, high treatment costs and ongoing reinfection risk suggest it could still play a role. We compared the impact of HCV vaccination amongst PWID against providing HCV treatment. METHODS: Dynamic HCV vaccination and treatment models among PWID were used to determine the vaccination and treatment rates required to reduce chronic HCV prevalence or incidence in the UK over 20 or 40 years. Projections considered a low (50% protection for 5 years), moderate (70% protection for 10 years) or high (90% protection for 20 years) efficacy vaccine. Sensitivities to various parameters were examined. RESULTS: To halve chronic HCV prevalence over 40 years, the low, moderate and high efficacy vaccines required annual vaccination rates (coverage after 20 years) of 162 (72%), 77 (56%) and 44 (38%) per 1000 PWID, respectively. These vaccination rates were 16, 7.6 and 4.4 times greater than corresponding treatment rates. To halve prevalence over 20 years nearly doubled these vaccination rates (moderate and high efficacy vaccines only) and the vaccination-to-treatment ratio increased by 20%. For all scenarios considered, required annual vaccination rates and vaccination-to-treatment ratios were at least a third lower to reduce incidence than prevalence. Baseline HCV prevalence had little effect on the vaccine's impact on prevalence or incidence, but substantially affected the vaccination-to-treatment ratios. Behavioural risk heterogeneity only had an effect if we assumed no transitions between high and low risk states and vaccinations were targeted or if PWID were high risk for their first year. CONCLUSIONS: Achievable coverage levels of a low efficacy prophylactic HCV vaccine could greatly reduce HCV transmission amongst PWID. Current high treatment costs ensure vaccination could still be an important intervention option.

[Update chronic viral hepatitis]. / Update chronische Virushepatitis.

More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade.

The role of a hepatitis C virus vaccine: modelling the benefits alongside direct-acting antiviral treatments.

BACKGROUND: Hepatitis C virus (HCV) elimination is being seriously considered globally. Current elimination models require a combination of highly effective HCV treatment and harm reduction, but high treatment costs make such strategies prohibitively expensive. Vaccines should play a key role in elimination but their best use alongside treatments is unclear. For three vaccines with different efficacies we used a mathematical model to estimate the additional reduction in HCV prevalence when vaccinating after treatment; and to identify in which settings vaccines could most effectively reduce the number of treatments required to achieve fixed reductions in HCV prevalence among people who inject drugs (PWID). METHODS: A deterministic model of HCV transmission among PWID was calibrated for settings with 25, 50 and 75% chronic HCV prevalence among PWID, stratified by high-risk or low-risk PWID. For vaccines with 30, 60 or 90% efficacies, different rates of treatment and vaccination were introduced. We compared prevalence reductions achieved by vaccinating after treatment to prevent reinfection and vaccinating independently of treatment history in the community; and by allocating treatments and vaccinations to specific risk groups and proportionally across risk groups. RESULTS: Vaccinating after treatment was minimally different to vaccinating independently of treatment history, and allocating treatments and vaccinations to specific risk groups was minimally different to allocating them proportionally across risk groups. Vaccines with 30 or 60% efficacy provided greater additional prevalence reduction per vaccination in a setting with 75% chronic HCV prevalence among PWID than a 90% efficacious vaccine in settings with 25 or 50% chronic HCV prevalence among PWID. CONCLUSIONS: Vaccinating after treatment is an effective and practical method of administration. In settings with high chronic HCV prevalence among PWID, even modest coverage with a low-efficacy vaccine could provide significant additional prevalence reduction beyond treatment alone, and would likely reduce the cost of achieving prevalence reduction targets.

Forgotten, not neglected: viral hepatitis in resource-limited settings, recall for action.

In 2010, the World Health Assembly adopted a resolution calling for interventions for the prevention and control of chronic viral hepatitis. These infectious diseases mostly affect resource-limited countries accounting for 80% of the world's population and facing numerous obstacles to contain the epidemic. At a time when morbidity and mortality of chronic liver disease have been considerably improved in wealthy countries by new innovative strategies and new potent antiviral drugs, it is now urgent to recall for concrete actions from stakeholders of global health policy to reduce the burden in resource-limited countries.

Prevention of hepatocellular carcinoma: a concise review of contemporary issues.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer deaths in men. Due to differences in the prevalence of viral hepatitis, the incidence of HCC in low and middle income countries is much higher than that of high income countries. Strategies to limit the impact of HCC include primary prevention against new cases of viral hepatitis, secondary prevention of HCC in susceptible individuals, and early HCC detection. Universal hepatitis B vaccination has resulted in dramatic reduction in incident cases of chronic hepatitis B and HCC in children and adolescents, and the full effect is expected in the next 20 years. The key hurdle for universal vaccination is the cost and the accessibility in low and middle income countries. Randomized controlled trials and meta-analyses showed that successful treatment of chronic hepatitis B and C can reduce the risk of HCC and cirrhotic complications. HCC surveillance by regular ultrasound examination and alpha fetoprotein testing leads to early cancer detection and offers the opportunity for curative treatment. Since all these measures are costly and require manpower and infrastructure support, the implementation should rely on the liaison among healthcare providers and policymakers. The cost-effectiveness of various strategies should also be studied based on local situations.

Cost-effectiveness analysis of a hypothetical hepatitis C vaccine compared to antiviral therapy.

We propose a mathematical model to simulate the dynamics of hepatitis C virus (HCV) infection in the state of São Paulo, Brazil. We assumed that a hypothetical vaccine, which cost was taken to be the initial cost of the vaccine against hepatitis B exists and it is introduced in the model. We computed its cost-effectiveness compared with the anti-HCV therapy. The calculated basic reproduction number was 1.20. The model predicts that without intervention a steady state exists with an HCV prevalence of 3%, in agreement with the current epidemiological data. Starting from this steady state three interventions were simulated: indiscriminate vaccination, selective vaccination and anti-HCV therapy. Selective vaccination proved to be the strategy with the best cost-effectiveness ratio, followed by indiscriminate vaccination and anti-HCV therapy.

[The viral hepatitis and its economic significance and prevention].

The reference of only part of diseases having contagious nature to the infectious pathology is closely related to the tradition of considering the infections as highly contagious diseases inclined to epidemic propagation. The data is presented related to the morbidity of viral hepatitis among the population of the City of Krasnodar. The corresponding economic losses and the achievements of medical preventive activities considering the social economic and other characteristics of the specific socium are considered.

Recent advances in antiviral agents: established and innovative therapies for viral hepatitis.

The management of HBV or HCV has improved dramatically over the last decade with the development of new drugs. This paper provides a review of new available and developing treatment options for HBV and HCV associated liver diseases. In the closer future the most realistic therapeutical option for most of the patients with HBV and HCV infection will be combination and/or long-term usage of the new, stronger antiviral drugs, if they maintain good safety profiles, achieve low resistance rates and will be available at lower prices.

Projected cost-effectiveness of new vaccines for adolescents in the United States.

BACKGROUND: Economic assessments that guide policy making on immunizations are becoming increasingly important in light of new and anticipated vaccines for adolescents. However, important considerations that limit the utility of these assessments, such as the diversity of approaches used, are often overlooked and should be better understood. OBJECTIVE: Our goal was to examine economic studies of adolescent vaccines and compare cost-effectiveness outcomes among studies on a particular vaccine, across adolescent vaccines, and between new adolescent vaccines versus vaccines that are recommended for young children. METHODS: A systematic review of economic studies on immunizations for adolescents was conducted. Studies were identified by searching the Medline, Embase, and EconLit databases. Each study was reviewed for appropriateness of model design, baseline setup, sensitivity analyses, and input variables (ie, epidemiologic, clinical, cost, and quality-of-life impact). For comparison, the cost-effectiveness outcomes reported in key studies on vaccines for younger children were selected. RESULTS: Vaccines for healthy adolescents were consistently found to be more costly than the health care or societal cost savings they produced and, in general, were less cost-effective than vaccines for younger children. Among the new vaccines, pertussis and human papillomavirus vaccines were more cost-effective than meningococcal vaccines. Including herd-immunity benefits in studies significantly improved the cost-effectiveness estimates for new vaccines. Differences in measurements or assumptions limited further comparisons. CONCLUSION: Although using the new adolescent vaccines is unlikely to be cost-saving, vaccination programs will result in sizable health benefits.

Immunogenicity of a recombinant, yeast-derived, anti-hepatitis-B vaccine after alternative dosage and schedule vaccination in Pakistani children.

A controlled, randomized trial was conducted in urban areas of Karachi and Lahore with the aim to look for ways to improve the cost-effectiveness of hepatitis B vaccination. Children under 15 years old (including neonates) were selected and screened for immunization by three regimens according to the frequency and doses of the recombinant vaccine used (Heberbiovac HB, Heber Biotec, Havana). Group A received 10 microg at 0, 1 months; group B (control) received 10 microg at 0, 1 and 2 months (standard regime), and group C received 5 microg at 0, 1 and 2 months. Antibody levels were titrated 2 months after the last dose. Cut-off for seroprotection and hyperresponse were taken as 10 and 100 IU/L, respectively. Nine hundred and ninety children were included and evaluated after discarding those positive for serological hepatitis virus infection markers. Seroprotection rates were 100, 99.7 and 99.7%, and hyperresponse was achieved by 92.7, 99.4, and 97% of the vaccinees in groups A, B, and C, respectively. The same good result was obtained in extreme ages subgroups (< or =1 year and > or =10 years old). The 1-year follow up of the children from Karachi showed good persistence of seroprotection (98, 100, and 99.4%) and hyperresponse (79.7, 96.7, and 87.4%). It is concluded that it is feasible to improve the cost-benefit ratio and compliance of hepatitis B vaccination by means of a two-shots or reduced dose schedule of the vaccine employed in the trial.

Potential cost-effectiveness of a preventive hepatitis C vaccine in high risk and average risk populations in Canada.

Hepatitis C virus (HCV) vaccine development remains at an early stage. We explored the economic and health consequences of potential HCV vaccines by comparing universal vaccination with a hepatitis C vaccine to no vaccination in two groups: (1) injecting drug users (IDU); (2) all 12 year olds, using a Markov cohort simulation. Among IDUs, vaccination would avert 248 cases of HCV infection and 89 HCV-related deaths per 1000 individuals, and reduce costs. In average risk cohorts, vaccination did not reduce costs but was reasonably cost effective. These results provide encouragement to vaccine developers that a vaccine that is moderately effective and reasonably priced should not face economic barriers to implementation and will be attractive to third party payers.