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.

Hepatitis E vaccine in China: Public health professional perspectives on vaccine promotion and strategies for control.

BACKGROUND: A hepatitis E (HepE) vaccine was developed and released in China in 2011. Uptake is currently very limited. The aims of this study were to characterize what public health professionals thought about promoting the HepE vaccine in Shanghai, China, and to develop realistic goals for the HepE vaccine based on this information. METHODS: Public health professionals from Shanghai and other jurisdictions of China were contacted to participate in in-depth qualitative interviews between October 2017 and August 2018. Participants were asked about their perception of the HepE vaccine roll-out. Codes were initially based on the structure of the questionnaire. Subsequently, similar ideas were further developed into themes based on what was present in the transcript data. RESULTS: Thirty-five individuals participated. Major topics of discussion included (1) clarifying the roles and responsibilities of private and public institutions in promoting and marketing the HepE vaccine, (2) identifying what methods of promotion were most efficient, and, (3) endeavoring to formulate a reasonable and realistic goal, if any, for HepE prevention and control in China. Participants emphasized that public sector sources can be trusted sources of information (although the private vaccination company can also be useful in disseminating information) and social media such as WeChat can be good ways to disseminate articles (although netizens may be worried about the spread of fake news). Vaccine promotion is restrained given limited levels of knowledge in the government, hospitals, and public health vaccination centers. CONCLUSION: Successful promotion and use of this vaccine in China, even in limited settings (for instance, certain workplaces, or certain groups) could provide additional information on long-term safety and could promote its adoption in other regions of the world where HepE has high morbidity among pregnant women and other populations.

Willingness to participate in hepatitis C vaccine trials among socially marginalized people who use drugs.

A major complicating factor for hepatitis C virus (HCV) vaccine clinical trial design and implementation is engagement and retention of people who use drugs (PWUD). Informed willingness to participate (WTP) in vaccine trials has emerged as a critical issue to describe, understand, and promote among populations at increased risk of communicable disease incidence. The present study addressed this topic by examining correlates of WTP among 320 socially marginalized PWUD as part of the Edmonton Drug Use and Health Survey (EDUHS). WTP was analyzed in relation to: gender, age, housing stability, ethnicity; self-reported hospital care in the past six months, self-reported injection drug use in the past 6 months, lifetime addiction treatment for alcohol or drugs, severity of drug use problems, and unmet healthcare needs. EDUHS participants reported high rates of current injection drug use (91%), and about two-thirds (67.3%) reported a lifetime HCV positive status. HCV positive respondents were older, had more severe substance use problems, and reported injecting drugs more frequently, compared to HCV negative respondents. Among the subsample of HCV negative respondents, 81% affirmed that they would be willing to enroll in a HCV vaccine prevention trial. Those reporting WTP were more likely to have had a recent hospital admission, to report more total unmet healthcare needs, and greater unmet needs for information, hospital care, and counseling, compared to HCV negative respondents not willing to enroll in a vaccine trial. No association was observed between WTP and other assessed variables. Results suggest that connecting PWUD not infected with HCV to local healthcare resources may be important in motivating vaccine trial participation.

Hepatitis B virus prevalence and risk factors in hard-to-reach Turkish population living in Belgium: A protocol for screening.

BACKGROUND: Hepatitis B virus (HBV) infection is an important public health problem in the Turkish population, that is, one of the largest migrant populations in Europe. With the introduction of cost-effective antiviral treatments in the past decade, there is a need to identify HBV-infected patients who may benefit from treatment. This study describes the design of a study to assess the HBV prevalence in the Turkish population living in Belgium. Additionally, we will determine the risk factors of HBV infection and the uptake of screening, vaccination, and antiviral treatment in this hard-to-reach Turkish population. METHODS: A longitudinal, epidemiological study will be conducted in the region Middle Limburg Belgium, where the Turkish adult population, 18 years of age and older, will be screened for hepatitis B surface antigen (HBsAg), antibodies against HBsAg (anti-HBs), and antibodies against hepatitis B core antigen (anti-HBc). Educational meetings concerning viral hepatitis B will be organized and there will be 3 ways to be screened for HBV: immediately after the educational meetings, at the Outpatient Hepatology Department of Ziekenhuis Oost-Limburg, and at home visits. Subsequently, participants will be asked to fill in a questionnaire regarding sociodemographic factors, migration history, risk factors for HBV infection (e.g., sharing toothbrushes, HBV-infected family member), and HBV vaccination status. Six months after screening, HBsAg-positive patients will be assessed whether they are under follow-up at the general practitioner or hepatologist. We will also gather information regarding the uptake of vaccination in nonimmunized subjects. DISCUSSION: This study will provide information about the HBV prevalence and distribution of the stages of liver disease in the Turkish population in Belgium. By determining the risk factors for HBV infection, subgroups with an increased prevalence of HBV infection can be identified. CLINICAL TRIAL NUMBER: This clinical trial is registered at clinicaltrials.gov (NCT03396458).

Modeling indicates efficient vaccine-based interventions for the elimination of hepatitis C virus among persons who inject drugs in metropolitan Chicago.

BACKGROUND AND AIMS: Persons who inject drugs (PWID) are at highest risk for acquiring and transmitting hepatitis C (HCV) infection. The recent availability of oral direct-acting antiviral (DAA) therapy with reported cure rates >90% can prevent HCV transmission, making HCV elimination an attainable goal among PWID. The World Health Organization (WHO) recently proposed a 90% reduction in HCV incidence as a key objective. However, given barriers to the use of DAAs in PWID, including cost, restricted access to DAAs, and risk of reinfection, combination strategies including the availability of effective vaccines are needed to eradicate HCV as a public health threat. This study aims to model the cost and efficacy of a dual modality approach using HCV vaccines combined with DAAs to reduce HCV incidence by 90% and prevalence by 50% in PWID populations. METHODS: We developed a mathematical model that represents the HCV epidemic among PWID and calibrated it to empirical data from metropolitan Chicago, Illinois. Four medical interventions were considered: vaccination of HCV naive PWID, DAA treatment, DAA treatment followed by vaccination, and, a combination of vaccination and DAA treatment. RESULTS: The combination of vaccination and DAAs is the lowest cost-expensive intervention for achieving the WHO target of 90% incidence reduction. The use of DAAs without a vaccine is much less cost-effective with the additional risk of reinfection after treatment. Vaccination of naïve PWID alone, even when scaled-up to all reachable PWID, cannot achieve 90% reduction of incidence in high-prevalence populations due to infections occurring before vaccination. Similarly, the lowest cost-expensive way to halve prevalence in 15 years is through the combination of vaccination and DAAs. CONCLUSIONS: The modeling results underscore the importance of developing an effective HCV vaccine and augmenting DAAs with vaccines in HCV intervention strategies in order to achieve efficient reductions in incidence and prevalence.

Molecular evolution and phylodynamics of hepatitis B virus infection circulating in Iran.

Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored. After sampling from the posterior distribution of the nucleotide substitution rate and other evolutionary parameters, the point estimations (median) of these parameters were obtained. All Iranian HBV isolates were of genotype D, sub-type ayw2. The origin of HBV is regarded as having evolved first on the eastern border, before moving westward, where Isfahan province then hosted the virus. Afterwards, the virus moved to the south and west of the country. The tMRCA of HBV in Iran was estimated to be around 1894, with a 95% credible interval between the years 1701 and 1957. The effective number of infections increased exponentially from around 1925 to 1960. Conversely, from around 1992 onwards, the effective number of HBV infections has decreased at a very high rate. Phylodynamic inference clearly demonstrates a unique homogenous pattern of HBV genotype D compatible with a steady configuration of the decreased effective number of infections in the population in recent years, possibly due to the implementation of blood donation screening and vaccination programs. Adequate molecular epidemiology databases for HBV are crucial for infection prevention and treatment programs.

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.

Why highly effective drugs are not enough: the need for an affordable solution to eliminating HCV.

INTRODUCTION: Because of the rapid pace of development of new direct-acting antiviral (DAA) drugs, chronic hepatitis C virus (HCV) infection is now increasingly considered curable. However, the emphasis on DAA therapies disregards key issues related to cost, availability, and antiviral resistance. Areas covered: This perspective provides an overview of current HCV therapies and the development of DAAs, followed by a discussion of the limitations of DAA therapy. A literature search was used to select relevant studies, and a web search for relevant news articles and press releases was conducted. Expert commentary: Despite cure rates exceeding 90%, now is not the time to declare victory against HCV but to reinforce recent progress by addressing the issues of cost and availability as well as by developing strategies to manage antiviral resistance. Future drug development efforts should place greater emphasis on targeting host factors required for HCV replication, for which the barrier to resistance is higher, and effort should continue to develop a vaccine against HCV. Finally, efforts should be made to facilitate large-scale screening in endemic areas to identify and treat patients as early as possible to reduce long-term risks of advanced liver disease and their attendant costs of management.

[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.