Revaccination for Hepatitis B in Previous Nonresponders Following Hepatitis C Eradication.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) do not respond to hepatitis B virus (HBV) vaccination as efficiently as the general population. We assessed if revaccination after HCV treatment resulted in improved response. METHODS: Previous HBV vaccine nonresponders were prospectively recruited for revaccination after HCV eradication. Hepatitis B surface antibody (HBsAb) testing was performed 1 month after series completion. RESULTS: Follow-up HBsAb testing was performed in 31 of 34 enrolled patients with 21 (67.7%) reactive results. There were no significant differences in HBsAb reactivity based on age, sex, race, or advanced fibrosis presence. CONCLUSIONS: HBV vaccine nonresponders should be considered for revaccination following HCV cure.

Hepatocellular Carcinoma Prevention in the Era of Hepatitis C Elimination.

The hepatitis C virus (HCV), a single-stranded RNA virus belonging to the Flaviviridae family, is a major cause of hepatocellular carcinoma (HCC) worldwide. Tumors caused by HCC have an increased mortality rate globally, which is more accentuated in Western countries. The carcinogenic potential of this virus is mediated through a wide range of mechanisms, spanning from the induction of chronic inflammation to oxidative stress and deregulation of cellular pathways by viral proteins. As the number of new infections continues unabated, HCC-related mortality should be prioritized through early detection, continued prevention of HCV transmission, and treatment of HCV with safe and efficacious direct antiviral agents (DAAs). People who inject drugs (PWID) are a significant reservoir of new HCV infections globally, and in order to eliminate hepatitis C as a global health threat, as set out by the World Health Organization, an integrated approach based on the optimization of care delivery and increased access to harm reduction and treatment for PWID is needed. Thanks to the development of safe and effective antiviral agents, eradication of the infection is now possible in almost all treated patients, leading to a significant reduction but not the elimination of the risk for HCC in cured patients. This is particularly relevant among aged populations who have cofactors of morbidity known to accelerate HCC progression, such as diabetes, obesity, and excessive alcohol consumption. Given the restless accumulation of individuals with cured HCV infection, the implementation of risk-stratified surveillance programs becomes impellent from a cost-effectiveness perspective, whereas the availability of a performant biomarker to predict HCC in cured patients remains an unmet clinical need.

Controlled Human Infection Model for Hepatitis C Virus Vaccine Development: Trial Design Considerations.

The design of a clinical trial for a controlled human infection model (CHIM) to accelerate hepatitis C virus (HCV) vaccine development requires careful consideration. The design of a potential approach to HCV CHIM is outlined, involving initial sentinel cohorts to establish the safety and curability of the viral inoculum followed by larger cohorts to establish the spontaneous clearance rate for each inoculum. The primary endpoint would be HCV clearance by 24 weeks post-inoculation, recognizing that the prevention of chronic infection would be the primary goal of HCV vaccine candidates. Additional considerations are discussed, including the populations to be enrolled, the required monitoring approach, indications for antiviral therapy, and the required sample size for different CHIM approaches. Finally, safety considerations for CHIM participants are discussed.

Chronic hepatitis C virus infections in Switzerland in 2020: Lower than expected and suggesting achievement of WHO elimination targets.

In this multi-method study, we investigated the prevalence of chronic infections with the hepatitis C virus (HCV) in Switzerland in 2020, and assessed Switzerland's progress in eliminating HCV as a public health problem by 2030 with regard to the World Health Organization (WHO) criteria targeting infections acquired during the preceding year ('new transmissions') and HCV-associated mortality. Based on a systematic literature review, the reappraisal of a 2015 prevalence analysis assuming 0.5% prevalence among the Swiss population and data from many additional sources, we estimated the prevalence among subpopulations at increased risk and the general population. For new transmissions, we evaluated mandatory HCV notification data and estimated unreported new transmissions based on subpopulation characteristics. For the mortality estimate, we re-evaluated a previous mortality estimate 1995-2014 based on new data on comorbidities and age. We found a prevalence of ≤0.1% among the Swiss population. Discrepancies to the 2015 estimate were explained by previous (i) underestimation of sustained virologic response numbers, (ii) overestimation of HCV prevalence among PWID following bias towards subgroups at highest risk, (iii) overestimation of HCV prevalence among the general population from inclusion of high-risk persons and (iv) underestimation of spontaneous clearance and mortality. Our results suggest that the WHO elimination targets have been met 10 years earlier than previously foreseen. These advancements were made possible by Switzerland's outstanding role in harm-reduction programmes, the longstanding micro-elimination efforts concerning HIV-infected MSM and nosocomial transmissions, little immigration from high-prevalence countries except Italian-born persons born before 1953, and wealth of data and funding.

Current Hepatitis C Vaccine Candidates Based on the Induction of Neutralizing Antibodies.

The introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C treatment. Short courses of treatment with these drugs are highly beneficial to patients, eliminating hepatitis C virus (HCV) without adverse effects. However, this outstanding success is tempered by the continuing difficulty of eradicating the virus worldwide. Thus, access to an effective vaccine against HCV is strongly needed to reduce the burden of the disease and contribute to the elimination of viral hepatitis. The recent failure of a T-cell vaccine based on the use of viral vectors expressing the HCV non-structural protein sequences to prevent chronic hepatitis C in drug users has pointed out that the induction of neutralizing antibodies (NAbs) will be essential in future vaccine candidates. To induce NAbs, vaccines must contain the main target of this type of antibody, the HCV envelope glycoproteins (E1 and E2). In this review, we summarize the structural regions in E1 and E2 proteins that are targeted by NAbs and how these proteins are presented in the vaccine candidates currently under development.

Editorial: Effective Direct-Acting Antiviral Treatments Support Global and National Programs to Eliminate Hepatitis C.

Eliminating an infectious disease aims to result in no residual disease in a specific geographic area due to deliberate efforts, which may require ongoing control measures to prevent the re-establishment of infection transmission. Currently, no effective vaccines prevent hepatitis C virus (HCV) infection. However, during the past decade, oral direct-acting antivirals (DAAs) have been developed and approved for the treatment of HCV that result in a 'cure' in more than 95% of people infected. Morbidity and mortality from untreated hepatitis C result from liver failure, cirrhosis, and HCC and can be prevented by curative treatment with DAAs, which also prevents HCV transmission. Morbidity and mortality from untreated hepatitis C result from liver failure, cirrhosis, and HCC and can be prevented by curative treatment with DAAs, which also prevents HCV transmission. In May 2016, the World Health Assembly of the World Health Organization (WHO) proposed the first global health initiative on viral hepatitis, which proposed the elimination of hepatitis B and C by 2030. In March 2023, the US President announced that in the 2024 fiscal year budget proposal, a 5-year program was approved to eliminate hepatitis C in the US, using a screening and treatment approach. This Editorial aims to present the development of effective and curative DAA treatments for hepatitis C that support the WHO and US Federal programs for disease elimination.

Toward a vaccine against hepatitis C virus.

Recent advances aid the development of vaccines to prevent chronic liver diseases.

Cost-effectiveness and economic investment to eliminate chronic hepatitis C in Mexico.

In July 2020, the Mexican Government initiated the National Program for Elimination of Hepatitis C (HCV) under a procurement agreement, securing universal, free access to HCV screening, diagnosis and treatment for 2020-2022. This analysis quantifies the clinical and economic burden of HCV (MXN) under a continuation (or end) to the agreement. A modelling and Delphi approach was used to evaluate the disease burden (2020-2030) and economic impact (2020-2035) of the Historical Base compared to Elimination, assuming the agreement continues (Elimination-Agreement to 2035) or terminates (Elimination-Agreement to 2022). We estimated cumulative costs and the per-patient treatment expenditure needed to achieve net-zero cost (the difference in cumulative costs between the scenario and the base). Elimination is defined as a 90% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage and 65% reduction in mortality by 2030. A viraemic prevalence of 0.55% (0.50-0.60) was estimated on 1st January 2021, corresponding to 745,000 (95% CI 677,000-812,000) viraemic infections in Mexico. The Elimination-Agreement to 2035 would achieve net-zero cost by 2023 and accrue 31.2 billion in cumulative costs. Cumulative costs under the Elimination-Agreement to 2022 are estimated at 74.2 billion. Under Elimination-Agreement to 2022, the per-patient treatment price must decrease to 11,000 to achieve net-zero cost by 2035. The Mexican Government could extend the agreement through 2035 or reduce the cost of HCV treatment to 11,000 to achieve HCV elimination at net-zero cost.

A National Hepatitis C Elimination Program in the United States: A Historic Opportunity.

This Viewpoint introduces a proposed 5-year program from the Biden-Harris administration that would use direct-acting antivirals to eliminate hepatitis C in the United States.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Defer no more: advances in the treatment and prevention of chronic hepatitis C virus infection in children.

PURPOSE OF REVIEW: Direct-acting antiviral (DAA) regimens targeting hepatitis C virus (HCV) are now approved for young children. This review examines recent DAA experience in children, current treatment recommendations and challenges, and potential treatment-as-prevention strategies. RECENT FINDINGS: In 2021, the US FDA extended approval of two pan-genotypic DAA regimens, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, to children as young as age 3 years based on high success rates and reassuring safety profiles in registry trials. Similar performance has been replicated with real-world DAA use in thousands of adolescents and in limited reports of children with high-risk conditions, including cirrhosis, cancer, thalassemia and HIV-coinfection. Treatment without delay is now recommended in the USA for viremic children aged 3 years and up to prevent disease progression and future spread. To date, treatment expansion is limited by high rates of undiagnosed paediatric infection. Universal prenatal screening will aid identification of perinatally exposed newborns, but new strategies are needed to boost testing of exposed infants and at-risk adolescents. Postpartum treatment programmes can prevent subsequent vertical transmission but are hampered by low rates of linkage to care and treatment completion. These challenges may be avoided by DAA use in pregnancy, and this warrants continued study. SUMMARY: Paediatric HCV is now readily curable. Substantial clinical and public health effort is required to ensure widespread uptake of this therapeutic breakthrough.

Elimination of HCV in Russia: Barriers and Perspective.

Hepatitis C virus (HCV) is highly prevalent in Russia, representing the largest pool of hepatitis C patients in Europe. Effective treatment regimens with direct-acting antivirals can achieve HCV cure in all patients; therefore, in 2016 the World Health Organization proposed eliminating hepatitis C as a public health threat by 2030. However, only a small number of countries are on track to meet the WHO's hepatitis C elimination targets by 2030 due to many barriers in healthcare systems. This review focuses on a discussion about the epidemiology of HCV in Russia, the economic burden of HCV-related diseases, and treatment access with particular reference to the barriers for the elimination of HCV.

Educating Primary Care Providers and Associate Care Providers About Hepatitis C Screening of Baby Boomers: a Multi-practice Study.

Chronic hepatitis C virus (HCV) increases the risk for hepatocellular carcinoma. Despite higher prevalence of HCV in persons born 1945-1965 (baby boomer), screening has not been widely adopted. Both primary care providers (PCPs) and associate care providers (ACPs) need to be educated about the rationale and methods to screen for HCV. In five Federally Qualified Health Centers serving low-income Hispanic communities, PCPs and ACPs attended a 50-min training lecture about HCV epidemiology, screening methods, and evaluation. Using a 12-item questionnaire, knowledge and attitudes were compared for PCPs and ACPs at baseline (pre-test) and following training (post-test). A higher proportion of PCPs correctly answered 3 of 6 knowledge questions on both pre-test and post-test but ACPs' showed more improvement in knowledge (all P < 0.05). ACPs had more favorable attitudes about linking patients to care on pre- and post-tests than PCPs, and ACPs' attitudes improved on all 6 items versus 4 for PCPs. Both PCPs and ACPs improved knowledge and attitudes after training about HCV screening but ACPs had more favorable attitudes than PCPs. Engaging the entire primary care practice team in learning about HCV screening promotes knowledge and attitudes necessary for successful implementation.

Viral hepatitis amidst COVID-19 in Africa: Implications and recommendations.

Hepatitis, a significant cause of mortality worldwide, results in around 1.34 million deaths each year globally. Africa is not exempt from the plague of Hepatitis. Around 100 million estimated individuals are infected with Hepatitis B or C. Egypt has the highest prevalence of cases of Hepatitis followed by Cameroon and Burundi. The continent is severely affected by the onset of the COVID-19 pandemic, as the virus has added an additional burden on the already fragile continent. With the pandemic, it is presumable that Hepatitis like other viral diseases will pose a threat to collapsing healthcare system. Therefore, for Africa to become more resilient in the face of such menaces, including Hepatitis, further prevention policies are required to be implemented.

MICRO-ELIMINATION OF HEPATITIS C IN THE INCARCERATED POPULATION: IS IT REALLY POSSIBLE?

According to the World Health Organization, 71 million people live with chronic hepatitis C. The treatment of this disease requires assistance from specialized physicians and a highly complex health care system. The prison population has been recognized as being at a high risk of acquiring confinement-related infections, including viral hepatitis. Hepatitis C virus (HCV) infection is a primary cause of death owing to liver disease among liberty-deprived individuals. Generally, prisons do not have adequate isolation wards for persons with communicable diseases, and overcrowding is a risk factor for this population. Besides prison overcrowding, violence, poor sanitary conditions, low socioeconomic status, social isolation, and emotional instability are factors that can lead detainees to adopt unhealthy habits that make them more susceptible to infections, including HCV, and complicate effective treatment. The Criminal Execution Law 7, 210 of July 11, 1984, in Article 14, grants preventive and curative medical, dental, and pharmacological healthcare to detainees. However, adequate hepatitis C treatment is rarely provided at prisons owing to social stigma and lack of knowledge on the severity of this condition or because most detainees are unaware of their condition. Given the multiple limitations imposed by the prison system model, implementing measures to treat diseases effectively is challenging. However, it is possible to eliminate hepatitis C in prisons in the long term through the coordinated action of public health institutions and the prison system.

Australia could miss the WHO hepatitis C virus elimination targets due to declining treatment uptake and ongoing burden of advanced liver disease complications.

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia's progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.

Microeliminação da hepatite C na população carcerária: realmente possível? / Micro-elimination of hepatitis c in the incarcerated population: is it really possible?

ABSTRACT According to the World Health Organization, 71 million people live with chronic hepatitis C. The treatment of this disease requires assistance from specialized physicians and a highly complex health care system. The prison population has been recognized as being at a high risk of acquiring confinement-related infections, including viral hepatitis. Hepatitis C virus (HCV) infection is a primary cause of death owing to liver disease among liberty-deprived individuals. Generally, prisons do not have adequate isolation wards for persons with communicable diseases, and overcrowding is a risk factor for this population. Besides prison overcrowding, violence, poor sanitary conditions, low socioeconomic status, social isolation, and emotional instability are factors that can lead detainees to adopt unhealthy habits that make them more susceptible to infections, including HCV, and complicate effective treatment. The Criminal Execution Law 7, 210 of July 11, 1984, in Article 14, grants preventive and curative medical, dental, and pharmacological healthcare to detainees. However, adequate hepatitis C treatment is rarely provided at prisons owing to social stigma and lack of knowledge on the severity of this condition or because most detainees are unaware of their condition. Given the multiple limitations imposed by the prison system model, implementing measures to treat diseases effectively is challenging. However, it is possible to eliminate hepatitis C in prisons in the long term through the coordinated action of public health institutions and the prison system.

RESUMO De acordo com a Organização Mundial da Saúde, 71 milhões de pessoas vivem com hepatite C crônica. O tratamento dessa doença requer assistência de médicos especializados e um sistema de saúde de alta complexidade. A população carcerária tem sido reconhecida como sendo de alto risco de adquirir infecções relacionadas às condições de confinamento, incluindo hepatites virais. O vírus da hepatite C (VHC) é uma causa primária de morte por doença hepática em pessoas privadas de liberdade. Geralmente, as prisões não possuem locais adequados para isolamento de pessoas com doenças transmissíveis e a superlotação é um fator de risco para essa população. Além da superlotação das prisões, violência, más condições sanitárias, baixo nível socioeconômico, isolamento social e instabilidade emocional são motivos adicionais que induzem os detidos a praticar hábitos não saudáveis, que os tornam mais suscetíveis a certas infecções (incluindo VHC) e complicam o tratamento específico. A Lei de Execução Penal n. 7.210, de 11 de julho de 1984, em seu artigo 14, garante assistência preventiva e curativa à saúde, incluindo assistência médica, farmacêutica e odontológica aos detidos. No entanto, o tratamento adequado da hepatite C é raramente fornecido nas prisões devido estigma social ou falta de conhecimento de sua condição ou porque a maioria dos detidos não tem conhecimento de sua condição. Devido a múltiplas limitações impostas pelo modelo prisional, a implementação de medidas para o tratamento eficaz de doenças é desafiadora. No entanto, é possível eliminar a hepatite C em um ambiente prisional de longa permanência através de ações coordenadas de instituições de saúde pública e o sistema prisional.

Protocol: Prospective observational study aiming for micro-elimination of hepatitis C virus in Nagawa town: The Nagawa Project.

BACKGROUND: The World Health Organization has set a goal of hepatitis C virus (HCV) elimination by the year 2030. However, no regions in Japan have succeeded in eradicating HCV. Micro-elimination is an approach to attain hepatitis C eradication in which national eradication goals are applied to specific populations so that viral treatment and control efforts can move forward quickly and efficiently. In order to eradicate HCV from Japan, this study aims to achieve HCV micro-elimination in the town of Nagawa. METHODS AND DESIGN: The Nagawa Project is an ongoing, prospective, multiple-institution, observational study running from April 1, 2021, to March 31, 2024. All residents of Nagawa town, excluding those under 20 years of age, not consenting to the study, or unable to undergo health check-ups due to nursing care needs, will be included. If found to be HCV antibody-positive, the participant will be recommended to see a doctor in consideration of MAC-2 binding protein glycosylation isomer values. Then, the participant will undergo serum HCV RNA measurement with the real-time polymerase chain reaction by an attending physician. If the participant is HCV RNA-positive, he or she will be referred to a hepatologist for further evaluation. In the case of a definitive diagnosis of chronic hepatitis C, direct acting antiviral treatment will be initiated. Through this process, HCV will be systematically micro-eliminated from the region. DISCUSSION: The Nagawa Project will reveal the prevalence of chronic HCV in addition to the HCV eradication rate in Nagawa town towards achieving HCV micro-elimination. TRIAL REGISTRATION: This study is performed by Shinshu University School of Medicine and was registered as UMIN 000044114 on May 6, 2021.

Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up.

Unless urgently needed to prevent a pandemic, the development of a viral vaccine should follow a rigorous scientific approach. Each vaccine candidate should be designed considering the in-depth knowledge of protective immunity, followed by preclinical studies to assess immunogenicity and safety, and lastly, the evaluation of selected vaccines in human clinical trials. The recently concluded first phase II clinical trial of a human hepatitis C virus (HCV) vaccine followed this approach. Still, despite promising preclinical results, it failed to protect against chronic infection, raising grave concerns about our understanding of protective immunity. This setback, combined with the lack of HCV animal models and availability of new highly effective antivirals, has fueled ongoing discussions of using a controlled human infection model (CHIM) to test new HCV vaccine candidates. Before taking on such an approach, however, we must carefully weigh all the ethical and health consequences of human infection in the absence of a complete understanding of HCV immunity and pathogenesis. We know that there are significant gaps in our knowledge of adaptive immunity necessary to prevent chronic HCV infection. This review discusses our current understanding of HCV immunity and the critical gaps that should be filled before embarking upon new HCV vaccine trials. We discuss the importance of T cells, neutralizing antibodies, and HCV genetic diversity. We address if and how the animal HCV-like viruses can be used for conceptualizing effective HCV vaccines and what we have learned so far from these HCV surrogates. Finally, we propose a logical but narrow path forward for HCV vaccine development.