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.

[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.

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.

[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.

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.

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.

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.

Testing for antibody to hepatitis A to decrease the cost of hepatitis A prophylaxis with immune globulin or hepatitis A vaccines.

BACKGROUND: The introduction of new vaccines to prevent hepatitis A infection raises the question of the cost of these vaccines relative to immune globulin when short-term protection against hepatitis A is required. Since the prevalence of hepatitis A antibodies (anti-HAV) in the US population increases rapidly with age, testing for anti-HAV may decrease the cost of vaccination programs. METHODS: A cost-analysis model was developed that incorporates the cost of immune globulin or hepatitis A vaccine, the number of doses of vaccine, the cost of testing for anti-HAV in either commercial or public-sector laboratories, and the prevalence of anti-HAV in the general population by age. RESULTS: In comparison with hepatitis A vaccines, with expected costs between $10 and $25 per dose, use of immune globulin for postexposure prophylaxis or preexposure short-term (< or = 6 months) prophylaxis is much less expensive for all age groups. Testing for anti-HAV does not significantly diminish the cost of immune globulin regimens. In contrast, if anti-HAV testing is performed in a public-sector laboratory at $10 per test, and hepatitis A vaccine costs $10 per dose, testing reduces vaccination costs in those 40 years of age or older for a two-dose vaccine regimen and in those 30 years of age or older for a three-dose regimen. At the other end of the spectrum, if vaccine costs $35 per dose, commercial testing for anti-HAV at $25 per person reduces the costs in those 30 years of age or older if either a two- or three-dose regimen is elected. However, vaccine savings are realized in those 10 years and older if public-sector testing is performed and three doses of vaccine at $35 per dose are utilized. In an intermediate scenario of public-sector testing and vaccines costing $25 per dose, the cost would also be reduced in those 30 years old or older. CONCLUSIONS: Testing for anti-HAV in frequent travelers, international government, business, and volunteer workers, military personnel, etc, may be an effective means of decreasing costs of hepatitis A prevention.

New hepatitis A vaccines and their role in prevention.

The hepatitis A virus (HAV) accounts for 20 to 25% of clinically apparent hepatitis cases worldwide. It generally causes mild to moderately severe acute illness. The serological prevalence of this virus is high in underdeveloped countries where poor sanitary conditions facilitate the spread of the virus. The Sentinel Counties studies of the Centers for Disease Control in the US have identified a number of factors associated with the acquisition of HAV, including household members, homosexual men, children and caretakers in day-care facilities who come into contact with individuals who are incubating or in the early phases of HAV infection. Poor sanitary conditions, international travel and intravenous drug use promote the transmission of the virus. However, in 40% of cases, no risk factor can be identified. Immune globulin (IG), once used exclusively for the prevention of HAV infection, acts by provoking passive-active immunity. It prevents clinical disease but permits subclinical disease to develop. Unfortunately, IG provides protection for only 3 to 6 months, necessitating repeat inoculation for exposure extending over 180 days. More recently, a number of live-attenuated and formalin-inactivated HAV vaccines have been developed and studied. The vaccines are well tolerated and highly immunogenic, with only mild local adverse reactions. The suggested dose and schedule is 720 ELISA units of inactivated vaccine injected intramuscularly at 0, 1 and 6 months. A single intramuscular dose of 1440 ELISA units followed 6 to 12 months later by a further injection has also been approved by the FDA and is available in several European countries. 90% of vaccines achieve protective levels of anti-HAV after the first injection. Routine use of the HAV vaccine for pre-exposure prophylaxis is expected to replace IG in healthy adults travelling to endemic areas, children in day-care centres, military personnel, homosexual men, healthcare workers and residents in institutions for the mentally disabled.

The prevalence of hepatitis A antibodies among Israeli travellers and the economic feasibility of screening before vaccination.

BACKGROUND: Hepatitis A (HA) is the most common vaccine-preventable disease among travellers. The probability of contracting the disease depends on the endemicity in both the destination and country of origin of the traveller. The introduction of the new highly effective but expensive inactivated HA vaccine necessitates a re-evaluation of HA prevention policy. In highly developed countries all travellers require vaccination. In highly endemic areas the entire population is immune. In Israel, HA seroprevalence declined from 94% in the early 1970s to < 60% in the mid 1980s. Living in a country in which the HA endemicity is changing, we studied the current situation of HA seroprevalence among travellers and the cost-benefit of screening for HA IgG before vaccination. METHODS: Israeli travellers of all ages, (range 22-74 years) expecting to spend a considerable time abroad presented to the travel clinic for pre travel advice and vaccination. A brief medical history was taken, including history of jaundice. Blood for HA IgG testing was drawn. RESULTS: In the present study, 389 Israeli travellers were screened for HA IgG. Overall, 46% were seropositive: 26% in the 21-30 group (n = 102); 37% in the 31-40 group (n = 145); 62% in the 41-50 group (n = 62); and 79% in the > 50 group (n = 80). CONCLUSIONS: In countries where hepatitis A endemicity is changing, an evaluation of seroprevalence and then a cost benefit calculation should be made. In Israel, assuming a current cost of $130 for vaccination and $30 for the IgG test, it is economically valid to screen Israeli travellers > 30 years old for HAV IgG before vaccination. A formula is presented for calculating the cost benefit ratio in any country, based on local endemicity according to age group.

Cost-effectiveness of hepatitis A vaccination in healthcare workers.

OBJECTIVE: To study the cost-effectiveness of vaccination for hepatitis A. SETTING: Hypothetical analysis of students currently enrolled in medical school in the United States. METHOD: A Markov-based model was developed using data from the literature, actual hospital costs, and an annual discount rate of 5%. The incidence rate was based on the lowest annual rate for the US population during the past decade. RESULTS: Over the lifetimes of students currently in medical school, the model estimated that there would be 286 hepatitis A cases with four deaths and 107 lost years of life. With routine vaccination, these numbers would decrease to 17, 0.3, and 6, respectively. The costs per life-year saved and quality adjusted life-year saved were $58,000 and $47,000, respectively. Serologic screening prior to vaccination was less cost-effective than universal vaccination. If the incidence of hepatitis A was underestimated by a factor of 5, the cost per life-year saved would decrease to $5,500. If the incidence of hepatitis was underestimated by a factor of 10, vaccination would result in a net cost savings. CONCLUSION: We conclude that the cost per life-year saved by routine hepatitis A vaccination was similar to many other standard medical modalities. For routine vaccination of medical students to be cost-saving, the incidence rate for hepatitis A must be at least 10 times higher than the rate presently reported for the general population. Serological screening prior to vaccination was not cost-effective.

Cost-effectiveness analysis of hepatitis B vaccination strategies in Catalonia, Spain.

Hepatitis B virus (HBV) infection is an important public health problem all over the world. Vaccination is one way to prevent it, and several strategies can be used depending on endemicity, the main pattern of HBV transmission and the demographic structure of the population. In this study, an economic comparison of 3 vaccination strategies (mass adolescent vaccination, mass infant vaccination and mass combined vaccination) was performed in Catalonia, Spain. Screening pregnant women for HBV infection in combination with these strategies was also evaluated. Epidemiological models to analyse patterns of HBV infection with and without vaccination and to calculate HBV-associated costs were designed. Comparison between strategies was done using cost-effectiveness analysis from the perspective of the healthcare system. Epidemiological model results indicate that implementation of HBV vaccination could prevent as many as 104,778 new acute infections, and avoid up to 5239 chronic infections, 2096 cases of cirrhosis and 419 cases of hepatocarcinoma over a 20-year period in Catalonia. Cost-effectiveness analysis shows that mass adolescent vaccination is the most efficient strategy, with lower costs per avoided case than the other 2 strategies. When any of these strategies is complemented by screening for HBV in pregnant women, the number of avoided cases is always higher and the cost per avoided case decreases or remains unchanged.