Explore the vast range of titles available.

The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met. We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions. By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0–15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000–670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8–16·1) new infections and 1·5 million (1·4–1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78–82) reduction in incidence and a 61% (60–62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan. Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic. Wellcome Trust.

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. The complexity and uncertainty related to the geographic distribution of HCV infection and chronic hepatitis C, determination of its associated risk factors, and evaluation of cofactors that accelerate its progression, underscore the difficulties in global prevention and control of HCV. Because there is no vaccine and no post-exposure prophylaxis for HCV, the focus of primary prevention efforts should be safer blood supply in the developing world, safe injection practices in health care and other settings, and decreasing the number of people who initiate injection drug use.

Hepatitis C (HCV) is a curable chronic infection, but lack of treatment uptake contributes to ongoing morbidity and mortality. State and national strategies for HCV elimination emphasize the pressing need for people with HCV to receive treatment. To identify provider-perceived barriers that hinder the initiation of curative HCV treatment and elimination of HCV in the USA. Qualitative semi-structured interviews with 36 healthcare providers who have evaluated patients with HCV in New York City, Western/Central New York, and Alabama. Interviews, conducted between 9/2021 and 9/2022, explored providers' experiences, perceptions, and approaches to HCV treatment initiation. Transcripts were analyzed using hybrid inductive and deductive thematic analysis informed by established health services and implementation frameworks. We revealed four major themes: (1) Providers encounter professional challenges with treatment provision, including limited experience with treatment and perceptions that it is beyond their scope, but are also motivated to learn to provide treatment; (2) providers work toward building streamlined and inclusive practice settings-leveraging partnerships with experts, optimizing efficiency through increased access, adopting inclusive cultures, and advocating for integrated care; (3) although at times overwhelmed by patients facing socioeconomic adversity, increases in public awareness and improvements in treatment policies create a favorable context for providers to treat; and (4) providers are familiar with the relative advantages of improved HCV treatments, but the reputation of past treatments continues to deter elimination. To address the remaining barriers and facilitators providers experience in initiating HCV treatment, strategies will need to expand educational initiatives for primary care providers, further support local infrastructures and integrated care systems, promote public awareness campaigns, remove prior authorization requirements and treatment limitations, and address the negative reputation of outdated HCV treatments. Addressing these issues should be considered priorities for HCV elimination approaches at the state and national levels.

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.

Hepatitis B and C cause most cases of hepatitis in the United States and the world. The two diseases account for about a million deaths a year and 78 percent of world's hepatocellular carcinoma and more than half of all fatal cirrhosis. In 2013 viral hepatitis, of which hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common types, surpassed HIV and AIDS to become the seventh leading cause of death worldwide. The world now has the tools to prevent hepatitis B and cure hepatitis C. Perfect vaccination could eradicate HBV, but it would take two generations at least. In the meantime, there is no cure for the millions of people already infected. Conversely, there is no vaccine for HCV, but new direct-acting antivirals can cure 95 percent of chronic infections, though these drugs are unlikely to reach all chronically-infected people anytime soon. This report, the first of two, examines the feasibility of hepatitis B and C elimination in the United States and identifies critical success factors. The phase two report will outline a strategy for meeting the elimination goals discussed in this report.

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.

Background Chronic hepatitis C is a major public health burden. With new interferon-free direct-acting agents (showing sustained viral response rates of more than 98%), elimination of HCV seems feasible for the first time. However, as HCV infection often remains undiagnosed, screening is crucial for improving health outcomes of HCV-patients. Our aim was to assess the long-term cost-effectiveness of a nationwide screening strategy in Germany. Methods We used a Markov cohort model to simulate disease progression and examine long-term population outcomes, HCV associated costs and cost-effectiveness of HCV screening. The model divides the total population into three subpopulations: general population (GEP), people who inject drugs (PWID) and HIV-infected men who have sex with men (MSM), with total infection numbers being highest in GEP, but new infections occurring only in PWIDs and MSM. The model compares four alternative screening strategies (no/basic/advanced/total screening) differing in participation and treatment rates. Results Total number of HCV-infected patients declined from 275,000 in 2015 to between 125,000 (no screening) and 14,000 (total screening) in 2040. Similarly, lost quality adjusted life years (QALYs) were 320,000 QALYs lower, while costs were 2.4 billion EUR higher in total screening compared to no screening. While incremental cost-effectiveness ratio (ICER) increased sharply in GEP and MSM with more comprehensive strategies (30,000 EUR per QALY for total vs. advanced screening), ICER decreased in PWIDs (30 EUR per QALY for total vs. advanced screening). Conclusions Screening is key to have an efficient decline of the HCV-infected population in Germany. Recommendation for an overall population screening is to screen the total PWID subpopulation, and to apply less comprehensive advanced screening for MSM and GEP.

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.

The prison setting presents not only challenges, but also opportunities, for the prevention and treatment of HIV, viral hepatitis, and tuberculosis. We did a comprehensive literature search of data published between 2005 and 2015 to understand the global epidemiology of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and tuberculosis in prisoners. We further modelled the contribution of imprisonment and the potential impact of prevention interventions on HIV transmission in this population. Of the estimated 10·2 million people incarcerated worldwide on any given day in 2014, we estimated that 3·8% have HIV (389 000 living with HIV), 15·1% have HCV (1 546 500), 4·8% have chronic HBV (491 500), and 2·8% have active tuberculosis (286 000). The few studies on incidence suggest that intraprison transmission is generally low, except for large-scale outbreaks. Our model indicates that decreasing the incarceration rate in people who inject drugs and providing opioid agonist therapy could reduce the burden of HIV in this population. The prevalence of HIV, HCV, HBV, and tuberculosis is higher in prison populations than in the general population, mainly because of the criminalisation of drug use and the detention of people who use drugs. The most effective way of controlling these infections in prisoners and the broader community is to reduce the incarceration of people who inject drugs.

IntroductionIn Vietnam, people who inject drugs (PWID), who are the major population infected by hepatitis C virus (HCV), remain largely undiagnosed and unlinked to HCV prevention and care despite recommended universal hepatitis C treatment. The data on the outcomes of HCV treatment among PWID also remain limited in resource-limited settings. The DRug use & Infections in ViEtnam–hepatitis C (DRIVE-C) study examines the effectiveness of a model of hepatitis C screening and integrated care targeting PWID that largely uses community-based organisations (CBO) in Hai Phong, Vietnam. In a wider perspective, this model may have the potential to eliminate HCV among PWID in this city.Methods and analysisThe model of care comprises large community-based mass screening, simplified treatment with direct-acting antivirals (DAAs) and major involvement of CBO for PWID reaching out, linkage to care, treatment adherence and prevention of reinfection. The effectiveness of DAA care strategy among PWID, the potential obstacles to widespread implementation and its impact at population level will be assessed. A cost-effectiveness analysis is planned to further inform policy-makers. The enrolment target is 1050 PWID, recruited from the DRIVE study in Hai Phong. After initiation of pan-genotypic treatment consisting of sofosbuvir and daclatasvir administrated for 12 weeks, with ribavirin added in cases of cirrhosis, participants are followed-up for 48 weeks. The primary outcome is the proportion of patients with sustained virological response at week 48, that will be compared with a theoretical expected rate of 70%.Ethics and disseminationThe study was approved by Haiphong University of Medicine and Pharmacy's Ethics Review Board and the Vietnamese Ministry of Health. The sponsor and the investigators are committed to conducting this study in accordance with ethics principles contained in the World Medical Association's Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects). Informed consent is obtained before study enrolment. The data are anonymised and stored in a secure database. The study is ongoing. Results will be presented at international conferences and submitted to international peer-review journals.Trial registration numberNCT03537196.