Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study.

BACKGROUND: Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15-49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global prevalence of viraemic HCV in 2019 among women of childbearing age. METHODS: In this modelling study, we used previously developed models for 110 countries inputted with country-specific demographic and HCV epidemiology data. We did a literature review, searching PubMed, Embase, and grey literature for studies published between Jan 1, 2000, and June 30, 2018, reporting HCV antibody or viraemic prevalence in women of childbearing age. Studies from the literature review and studies in models were compared by use of a data quality scoring system and models were updated, as appropriate, when a better study was identified. We used these HCV disease burden models to calculate the 2019 prevalence of viraemic HCV in women of childbearing age. In countries without a model, prevalence was extrapolated by Global Burden of Disease (GBD) region. FINDINGS: An estimated 14 860 000 (95% uncertainty interval [UI] 9 667 000-18 282 000) women aged 15-49 years had HCV infection worldwide in 2019, corresponding to a viraemic prevalence of 0·78% (95% UI 0·62-0·86). Globally, HCV prevalence increased with age, rising from 0·25% (95% UI 0·20-0·27) in women aged 15-19 years to 1·21% (0·97-1·34) in women aged 45-49 years. China (16% of total infections) and Pakistan (15%) had the greatest numbers of viraemic infections, but viraemic prevalence was highest in Mongolia (5·14%, 95% CI 3·46-6·28) and Burundi (4·91%, 3·80-18·75). Of the countries with 500 cases or more, viraemic prevalence was lowest in Chile (0·07%, 95% UI 0·04-0·12). Among the GBD regions, eastern Europe had the highest viraemic prevalence (3·39%, 95% UI 1·88-3·54). By WHO region, the Eastern Mediterranean region had the highest viraemic prevalence (1·75%, 95% UI 1·26- 1·90). INTERPRETATION: Most research on HCV disease burden among women aged 15-49 years focuses on pregnant women. Using modelling, this analysis provides global and national estimates of HCV prevalence in all women of childbearing age. These data can inform preconception test-and-treat strategies to reduce vertical transmission and total disease burden. FUNDING: Gilead Sciences, John C Martin Foundation, private donors.

Value in Hepatitis C Virus Treatment: A Patient-Centered Cost-Effectiveness Analysis.

BACKGROUND: Innovations in hepatitis C virus (HCV) therapy included in traditional comparative evaluations focus on sustained virologic response (SVR) without addressing challenges patients report beyond virologic cure. This study aims to evaluate the cost-effectiveness of HCV drug therapy with a patient-centered approach. METHODS: An individual-based Markov model was constructed using guidance from a stakeholder advisory board (SAB), a patient Delphi panel, and published literature to evaluate direct-acting antivirals (DAAs) compared to no treatment. The United States (US) health sector and societal perspectives were considered for 10- and 20-year time horizons. Inputs for treatment costs and effectiveness reflect a generic regimen. Indirect costs used for the societal model included estimates from self-reported productivity in a matched-control sample. Beyond the traditional quality-adjusted life-year (QALY) health outcome, this study included two novel measures developed from the Delphi panel and SAB: infected life-years and workdays missed. All costs were measured in 2018 US dollars. RESULTS: Health sector costs and QALYs were higher in the treatment group in both 10- and 20-year models. Total infected life-years and workdays missed were reduced in the treatment group for both models. When costs of absenteeism, presenteeism, and patient/caregiver time were included, the DAA intervention was cost-saving at both 10 and 20 years. Health sector results were sensitive to drug costs and utility estimates for post-SVR health states. Societal results were sensitive to presenteeism estimates and drug costs. CONCLUSION: Treatment was cost-effective from a health sector perspective and cost-saving when including non-health costs such as patient/caregiver time and productivity.

Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study.

BACKGROUND: More than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857. FINDINGS: Our search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18-1·39). Globally, 1·5 million (95% CI 0·9-2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs. INTERPRETATION: HCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries. FUNDING: British Heart Foundation and Wellcome Trust.

What Matters Most for Treatment Decisions in Hepatitis C: Effectiveness, Costs, and Altruism.

OBJECTIVE: Comparative evaluations of innovations in hepatitis C virus (HCV) drug therapy typically focus on sustained virologic response (SVR) without addressing psychological and socioeconomic challenges that extend beyond virologic cure. This study aims to identify and prioritize variables important to patients when making the decision to start HCV treatment. METHODS: A three-round Delphi process was conducted with the first round derived from a systematic literature review and advisory board input, including patients who have been affected by HCV, physicians, pharmacists, and a patient group representative. Delphi panelists were HCV patients who had received treatment or were considering treatment. Panelists were asked about factors influencing their HCV treatment decisions. Thematic analysis of open-ended responses based on grounded theory was used. Agreement with each category and rankings based on order of importance from the patient perspective was reported. RESULTS: Treatment effectiveness (100% agreement), longer life (88%), fear of complications (84%), financial issues (80%), quality of life (100%), and impact on society (80%) were considered important factors to patients in decisions to seek treatment. A fear of harming others (87%) was considered more important than physical symptoms (83%) in terms of patient-reported problems caused by HCV. Medication costs (91%) were identified as the most important costs of having HCV, followed by doctor costs (77%). CONCLUSIONS: In addition to treatment effectiveness, patient experiences with financial problems, quality of life, and altruistic desires impact HCV patients' decisions. The risk of infecting others may motivate patients to seek treatment as much as personally experienced physical symptoms.

Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis.

BACKGROUND: With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV. METHODS: We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV. RESULTS: In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8-83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68-2.77). Over the past 26 years, the global population-attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%-0.56%) to 0.92% (95% CI, 0.55%-1.41%), and DALYs increased from 0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43-1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23-0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho. CONCLUSIONS: People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions. CLINICAL TRIAL REGISTRATION: URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.

A pilot study to expand treatment of chronic hepatitis C in resource-limited settings.

The past five years have seen a revolution in the treatment of chronic hepatitis C, as short duration oral regimens of direct-acting antiviral drugs (DAAs), with nearly 100% cure rates for all genotypes, have replaced longer courses of ribavirin and injected interferon. Although initially very expensive, these DAAs are now becoming available in generic equivalents in countries with large numbers of chronically infected people, such as India. However, a number of obstacles may hinder the delivery of these drugs in resource-limited settings, including lack of access to diagnostic testing and the restriction of treatment to a small number of medical specialists. New approaches are therefore needed to make DAAs available to the estimated 71 million infected people, many of whom disproportionately live in low- or middle-income countries. A recent pilot study (ASCEND) of hepatitis C management in a low-income population in Washington, D.C., demonstrated that trained nurse practitioners, primary care physicians and hepatologists were equally successful in diagnosing and treating patients, indicating that such an approach might be successful in resource-limited regions of the world. Members of the Global Virus Network have received funding to carry out a similar training project in a region of India with a high prevalence of hepatitis C. This paper reviews the challenges of delivering DAA therapy in low- and middle-income countries, describes plans for performing and evaluating the effectiveness of a training program in India, and discusses future needs for the eventual elimination of hepatitis C.