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In 2016, Asia and Pacific countries endorsed action plans for reaching viral hepatitis elimination targets set in the Global Health Sector Strategy (GHSS) for Viral Hepatitis 2016-2021. We examine the region's progress by modelling disease burden and constructing the cascade of care. Between 2015 and 2020, chronic HBV prevalence declined from 4.69% to 4.30%, and HCV prevalence declined from 0.64% to 0.58%. The region achieved the 2020 target of 30% incidence reduction for HBV, whereas HCV incidence declined by 6%. Hepatocellular carcinoma incidence for HBV and HCV increased by 9% and 7%, respectively. Liver-related deaths from HBV rose by 8%, and mortality attributable to HCV plateaued. Large testing and treatment gaps remained in 2019: only 13% of chronic HBV infections were diagnosed and 25% treated; 21% of chronic HCV infection were diagnosed and 11% treated. Viral hepatitis must become national priority with adequate funding to reach elimination goals by 2030.

As of 2019, the United States (US) was not on track to achieve targets for elimination, due to increasing incidence and treatment barriers. In 2020, the COVID-19 pandemic disrupted HCV services globally and in the US. As healthcare services normalize, there is an urgent need to reassess progress and evaluate scenarios that restore a pathway toward HCV elimination.We updated a validated Markov model to estimate HCV-related morbidity and mortality in the US. Five scenarios were developed to bookend possible HCV outcomes in the wake of the pandemic. These included 1) return to pre-COVID-19 treatment forecasts; 2) achieve elimination targets through treatment and harm reduction; 3) long-term treatment disruptions; 4/5) achieve elimination targets through increased treatment without increased harm reduction, starting in either 2022 or 2025.From 2014-2019, more than 1.2 million patients were treated for HCV in the US. Elimination targets in 2030 could be achieved in the US by treating an additional 3.2-3.3 million patients from 2020 to 2030, or by preventing new infections through expanded harm reduction programs and treating up to 2.7 million patients. Intervention scenarios could prevent over 30,000 HCC cases and over 29,000 liver-related deaths.The US has made strides toward HCV elimination, but gains could be lost in the wake of the pandemic. However, it is still possible to avert nearly 30,000 deaths through increased harm reduction and increased treatment rates. This requires a coordinated effort from the entire HCV community.

Summary 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.

Hepatitis C virus (HCV) prevalence estimates for adults and high-risk groups have been widely published, but the disease burden in children is poorly understood. Direct-acting antiviral drugs, which are considered to be highly effective curative therapies for HCV, are now approved for paediatric patients as young as 3 years. Reliable prevalence estimates for this population are needed to inform scale-up of treatment and national strategies. This analysis combines past modelling and epidemiological work in 104 countries and territories to estimate global HCV prevalence in children in 2018.In this modelling study, a comprehensive literature review for articles published between Jan 1, 2000, and March 31, 2019, was used to determine historical HCV prevalence estimates in children in all 249 countries and territories of the world. We identified published HCV prevalence estimates for children aged 0-18 years who are not at high risk of HCV infection in 39 countries and territories and inputted them into dynamic Markov disease-burden models to estimate viraemic HCV prevalence in 2018. For 25 of them, which had complete data, available information on HCV prevalence in children was used to build regression models to predict paediatric prevalence in an additional 65 countries and territories that had country-specific or territory-specific data about predictors only. Regression models were created for each 5-year paediatric age cohort from 0 to 19 years, considering several predictor variables. The data and forecasts from the 104 countries and territories for which data were available were used to calculate HCV prevalence by Global Burden of Disease region, which was then applied to the remaining 145 countries and territories to generate a global estimate.The global estimate for viraemic prevalence in the paediatric population aged 0-18 years was 0·13% (95% uncertainty interval 0·08-0·16), corresponding to 3·26 million (2·07-3·90) children with HCV in 2018. HCV prevalence increased with age in all countries and territories. HCV prevalence in women of childbearing age was the strongest predictor of HCV prevalence in children aged 0-4 years (p0·0001). Prevalence of HCV in adults was significantly associated with HCV prevalence in children aged 5-19 years (p0·0001), and the proportion of HCV infections in people who inject drugs was significantly associated with HCV prevalence in children aged 15-19 years (p=0·036).Most studies on HCV prevalence in children focus on high-risk groups and highly endemic geographic areas. Our analysis provides global prevalence estimates of HCV in the paediatric population. Treatment in paediatric patients requires different clinical and population health management optimisation than in adults. Because of this heterogeneity, country-specific or territory-specific and age-specific HCV prevalence estimates can help countries and territories to improve national HCV elimination strategies.Gilead Sciences, John C Martin Foundation, and private donors.

BACKGROUND Switzerland has made strides towards hepatitis C virus elimination, but as of 2019, elimination was not guaranteed. However, political interest in viral hepatitis has been increasing. We sought to develop a better understanding of Switzerland's progress towards HCV elimination and the profile of remaining HCV-RNA-positive patients. METHODS A previously described Markov model was updated with recent diagnosis and treatment data and run to generate new forecasts for HCV disease burden. Two scenarios were developed to evaluate HCV morbidity and mortality under the status quo and a scenario that achieves the Swiss Hepatitis Strategy Elimination targets. Next, an analysis was conducted to identify population segments bearing a high burden of disease, where future elimination efforts could be directed. RESULTS At the beginning of 2020, an estimated 32��100 viremic infections remained in Switzerland (0.37% viremic prevalence). Adult (���18��years of age) permanent residents born abroad represented the largest subpopulation, accounting for 56% of HCV infections. Thirteen countries accounted for ���60% of viremic infections amongst permanent residents born abroad, with most people currently residing in Zurich, Vaud, Geneva, Bern, Aargau and Ticino. Amongst Swiss-born HCV-RNA-positive persons, two-thirds had a history of IDU, corresponding to 33% of total infections. CONCLUSIONS In Switzerland, extra efforts for diagnosis and linkage to care are warranted in foreign-born populations and people with a history of drug use. Population-level measures (eg increasing the number of providers, increase screening) can identify patients who may have otherwise fallen through the gaps or avoided care because of stigma.

Background & Aims: In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID-19 pandemic, this analysis seeks to evaluate Sweden's progress towards the World Health Organization (WHO) elimination targets and identify remaining barriers. Methods: The data used for modelling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios (‘2019 Base’ and ‘WHO Targets’) were developed to evaluate Sweden's progress towards HCV elimination. Results: At the beginning of 2019, there were 29 700 (95% uncertainty interval: 19 300-33 700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment and liver-related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require (i) expanding harm reduction programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025. Conclusions: It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times. (Less)

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

Background: Since a 2016 analysis on the epidemiology and disease burden of HCV in Croatia, the HCV treatment paradigm has shifted substantially. Fibrosis restrictions were removed, and the number of patients treated tripled. With these encouraging changes to policy and practice, an updated analysis was completed to guide resource allocation and a national strategic plan for HCV elimination in Croatia. ----- Methods: A comprehensive literature review and discussions with in-country experts were used to identify epidemiological factors defining HCV disease burden in Croatia. An HCV disease burden model, seeded with this data, was used to assess the impact of increasing screening rates and delineate the steps needed to reach the World Health Organization’s (WHO) Global Health and Sector Strategy hepatitis C elimination targets. ----- Results: Achieving WHO elimination targets would reduce the number of viremic cases of HCV from 21,000 in 2015 to 4,000 by 2030 while averting 500 liver-related deaths, and 680 cases of hepatocellular carcinoma and decompensated cirrhosis from 2015 to 2030, relative to the projections under the current standard of care. Screening practices will need to ramp up to testing about 250,000 Croatians annually so that about 1,500 patients can be diagnosed and treated each year. ----- Conclusions: Elimination requires a coordinated effort between country and industry leaders including government authorities, policymakers and healthcare and insurance providers. Improved screening mechanisms will be needed for the scale-up required to achieve goals., Uvod: Nakon posljednje analize epidemioloških i kliničkih podataka o HCV infekciji iz 2016. godine došlo je do velikih promjena u paradigmi liječenja. Uklonjene su restrikcije vezane uz uznapredovali stadij fibroze jetre, a broj liječenih se utrostručio. S obzirom na ohrabrujuće činjenice u mogućnostima liječenja napravljena je nova analiza, koja će peciznije usmjeriti prioritete i alokaciju resursa za provedbu nacionalnog akcijskog plana za eliminaciju hepatitisa C.----- Metode: Opsežan pregled literature i razgovori s hrvatskim stručnjacima korišteni su za identificiranje epidemioloških čimbenika koji definiraju opterećenje bolešću uzrokovanom virusom hepatitisa C u Hrvatskoj. Dobiveni podatci korišteni su u postojećem matematičkom modelu za procjenu opterećenja bolešću uzrokovanom HCV-om (engl. HCV disease burden model), kako bi se procijenio učinak povećanih stopa probira (engl. screening) i zacrtao putokaz potrebnih koraka za dostizanje globalnih ciljeva Strategije Svjetske zdravstvene organizacije (SZO) za eliminaciju hepatitisa C. ----- Rezultati: Postizanje ciljeva SZO-a značilo bi redukciju HCV viremičnih slučajeva na 4.000 u 2030. uz sprječavanje 500 smrtnih ishoda uzrokovanih bolestima jetre i 680 slučajeva hepatocelularnog karcinoma i dekompenzirane ciroze u razdoblju od 2015. do 2030., za koje se procjenjuje da bi nastali uz sadašnju razinu probira i kliničku praksu. Prema upotrijebljenom matematičkom modelu to bi zahtijevalo povećanje broja testiranja na 250.000 osoba godišnje, kako bi se godišnje dijagnosticiralo i liječilo 1.500 pacijenata. ----- Zaključak: Eliminacija virusnih hepatitisa kompleksan je proces koji zahtijeva koordinirane aktivnosti i suradnju između medicinskih stručnjaka, državne politike, donositelja odluka i pružatelja zdravstvenog osiguranja. Povećanje opsega probirnog testiranja bit će ključno za postizanje ciljeva SZO-a u Hrvatskoj.

Background & Aims COVID-19 has placed significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in hepatitis C liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination program progress. Methods Previously developed models were adapted for 110 countries to include a status quo or “no delay” scenario and a “1-year delay” scenario assuming significant disruption in interventions (screening, diagnosis and treatment) in the year 2020. Annual, country-level, model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the “no-delay” estimates from the “1-year delay” estimates. Results The “1-year delay” scenario resulted in 44,800 (95% UI: 43,800 – 49,300) excess hepatocellular carcinoma (HCC) cases and 72,300 (95% UI: 70,600 – 79,400) excess liver-related deaths (LRDs), relative to the “no delay” scenario globally, from 2020-2030. Most missed treatments would be in lower-middle income countries, while most excess HCC and LRDs would be among high-income countries. Conclusions The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. In order to mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so., Graphical abstract, Highlights • With only 10 years left for hepatitis elimination, COVID-19 is impacting progress • A 1-year delay in HCV programs could cause excess HCV morbidity and mortality • A 1-year delay could cause 72,000 excess deaths from HCV • Most excess deaths would be in the lower middle income and high-income groups, COVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate.

Background and aims. Hepatitis C virus (HCV) elimination for Italy is an ambitious, but achievable goal. In Italy, there is political will, which aims to achieve the World Health Organization (WHO) elimination goals recognizing the need to identify undiagnosed individuals in key high-risk groups and in the general population, however there is concern regarding HCV treatment implementation in Italian Regions. Methods. A modelling analysis was conducted, using the “Italy Polaris” model, to forecast the impact of different HCV treatment rates in achieving the HCV elimination goals in Italy. The model assessed two treatment scenarios: 2018 Scenario and 2019 Scenario, using the annually HCV treatment rate in Italy. Results. Considering a high treatment rate, as assumed by the 2018 Scenario, all HCV elimination targets would be achieved. Considering the 2019 Scenario, in which a decreasing number of newly diagnosed individuals and as consequence, a decline in the number of treated patients, were assumed, only the 65% HCV mortality reduction would be an achievable goal in Italy. The other elimination targets could be achievable over 7 years later than the year 2030. Conclusions. Establishing an ad hoc fund for DAAs for each Italian Region, binding resources both for case finding, through active screening and activities for rapid linkage to care and treatment, is of paramount importance, in order to keep Italy on track to achieve the WHO elimination targets by 2030.

Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000–3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0·64% (95% UI 0·41–0·74). We estimated that 1 180 000 (95% UI 1 003 000–1 357 000) people were diagnosed with viraemia (36·4%), 150 000 (12 000–180 000) were treated (4·6% of the total infected population or 12·7% of the diagnosed population), 133 000 (106 000–160 000) were cured (4·1%), and 57 900 (43 900–67 300) were newly infected (1·8%) in 2015. Additionally, 30 400 (26 600–42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary. Funding Gilead Sciences.

BACKGROUND AND AIMS: A previous analysis of hepatitis C virus (HCV)-related healthcare costs in Switzerland found that the annual healthcare costs of untreated HCV infection (excluding antiviral treatment) could increase by more than 25 million Swiss francs (CHF) between 2013 and 2030. Since that publication, highly efficacious directacting antiviral therapies (DAAs) have become available, making HCV elimination a possibility. This analysis quantifies the clinical and economic burden of HCV intervention strategies over the next 15 years. METHODS: A model was developed to estimate the future clinical and economic burden of HCV infection if patients are diagnosed and treated according to a historical paradigm (historical base case), or at higher levels without treatment reimbursement restrictions (Scenario 1). The infected population was tracked by age- and sex-defined cohorts, and associated direct medical costs (healthcare, screening, diagnostics and treatment) and quality-adjusted life years (QALYs) were calculated. Direct cost savings and the incremental cost-effectiveness ratio (ICER) were calculated to assess the economic impact of each scenario. Additionally, we generated a net-zero cost scenario (Scenario 2), assuming the same treatment paradigm as Scenario 1 but at the treatment price that would break even by 2031. RESULTS: In the historical base case, annual direct costs are projected to decrease from 150 million (95% UI: 132–170 million) CHF in 2016 to 90 million (95% UI: 65–111 million) CHF in 2031. Cumulative direct costs are projected to reach 1.7 billion (95% UI: 1.2–2.0 billion) CHF by 2031. In Scenario 1, annual direct costs first increased to 175 million CHF by 2018, before declining to 44 million CHF by 2031. Cumulative direct costs in this scenario are projected to reach 1.8 billion CHF by 2031. For Scenario 2, the treatment price needed to achieve break-even by 2031 considering only direct costs would be 27,900 CHF per patient. By 2031, Scenarios 1 and 2 would gain 58,300 QALYs. In both scenarios, the ICER drops below the costeffectiveness threshold of 78,000 CHF in 2018. Over the 15-year span, the ICER was determined to be 2,200 CHF for Scenario 1. CONCLUSIONS: Increasing the number of patients treated and treating all fibrosis stages is cost-effective compared to the historical base case and could achieve breakeven by 2031 at a price of 27,900 CHF. Key words: hepatitis C virus, liver cirrhosis, hepatocellular carcinoma, Switzerland, cost-effectiveness, quality-adjusted life years, direct-acting antivirals

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate in simple terms the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of HCV-infected individuals to diagnosis, treatment and cure. The value of reporting would be enhanced if reporting entities utilized a standardized approach for generating their CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and ensuring the accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets

People who have recently injected drugs are a priority population in efforts to achieve hepatitis C virus (HCV) elimination. This study estimated the prevalence and number of people with recent injecting drug use living with HCV, and the proportion of people with recent injecting drug use among all people living with HCV infection at global, regional, and country-levels. Data from a global systematic review of injecting drug use and HCV antibody prevalence among people with recent (previous year) injecting drug use were used to estimate the prevalence and number of people with recent injecting drug use living with HCV. These data were combined with a systematic review of global HCV prevalence to estimate the proportion of people with recent injecting drug use among all people living with HCV. There are an estimated 6.1 million [95% uncertainty interval (UI) 3.4-9.2] people with recent injecting drug use aged 15-64 years living with HCV globally (39.2% viraemic prevalence; UI 31.6-47.0), with the greatest numbers in East and Southeast Asia (1.5 million, UI 1.0-2.1), Eastern Europe (1.5 million, UI 0.7-2.4), and North America (1.0 million, UI 0.4-1.7). People with recent injecting drug use comprise an estimated 8.5% (UI 4.6-13.1) of all HCV infections globally, with the greatest proportions in North America (30.5%, UI 11.7-56.7), Latin America (22.0%, UI 15.3-30.4), and Eastern Europe (17.9%, UI 8.2-30.9). Although globally about forty percent of people with recent injecting drug use are living with hepatitis C virus (HCV) and almost nine percent of all HCV infections globally occur among people with recent injecting drug use, there is wide variation among countries and regions. National Drug and Alcohol Research Centre, UNSW Sydney; Australian National Health and Medical Research Council; John C Martin Foundation.

PubMed: 29599078, 2-s2.0-85044540918, Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Methods: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Findings: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4–4·6), corresponding to 291 992 000 (251 513 000–341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6–2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2–1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. Funding: John C Martin Foundation. © 2018 Elsevier Ltd, H28-kansei-ippan-001 National Academy of Sciences, NAS Novartis Roche World Health Organization, WHO Gilead Sciences Alnylam Pharmaceuticals AbbVie Meso Scale Diagnostics, MSD British Microcirculation Society, BMS Japan Society for the Promotion of Science, JSPS: 17H03589 Ministry of Health, Labour and Welfare, MHLW Vetenskapsrådet, VR Siemens Universiteit Antwerpen OLL-683801, DR-S, IGa, SB, SMB, CE, KM, HMN, KP, KR-S, SR, JDS, and HR report grants from John C Martin Foundation, during the conduct of the study, and grants from Gilead Sciences, AbbVie, WHO, National Academy of Sciences, Intercept Pharmaceuticals, and Boehringer Ingelheim, outside the submitted work. MHN reports grants and personal fees from Bristol-Myers Squibb (BMS), Gilead Sciences, and Janssen, and personal fees from Novartis, Anylam, and Dynavax, outside the submitted work. PVD acts as chief and principal investigator for vaccine trials done on behalf of the University of Antwerp, Belgium, for which the University obtains research grants from vaccine manufacturers; speaker's fees for presentations on vaccines are paid directly to an educational fund held by the University of Antwerp, and PVD receives no personal remuneration for this work. ACA reports personal fees from Mylan Pharmaceuticals, outside the submitted work. JEA reports fees paid to his hospital for participation on the advisory boards of Gilead Sciences, ViiV Healthcare, BMS, Janssen, and AbbVie, and grants from BMS, Merck Sharp & Dohme (MSD), AbbVie, and ViiV Healthcare, outside the submitted work. TB reports grants, personal fees, and non-financial support from AbbVie and Gilead Sciences; grants and personal fees from BMS, Janssen, Roche, MSD, and Sequana Medical; and personal fees from Bayer, Vertex, Tibotec, Intercept, Sirtex, and Alexion, outside the submitted work. PB reports grants and personal fees from AbbVie, Gilead Sciences, and MSD, outside the submitted work. MBr reports personal fees from BMS, Gilead Sciences, and Janssen, and grants from BMS, outside the submitted work. HLYC reports personal fees from Gilead Sciences, BMS, AbbVie, Roche, MedImmune, and Intellia, outside the submitted work. PBC reports grants from AbbVie, Gilead Sciences, and MSD, outside the submitted work. VC reports personal fees from AbbVie, BMS, Gilead Sciences, and MSD, and grants from BMS, outside the submitted work. MCor reports personal fees from AbbVie, BMS, Boehringer Ingelheim, Biogen Idec, Falk Foundation, Gilead Sciences, Janssen, MSD, Roche Diagnostics, Roche Pharma, and Siemens, outside the submitted work. SD and PJ report personal fees and non-financial support from AbbVie and Gilead Sciences, and personal fees from MSD, outside the submitted work. MHE-S is an advisory board member for Perspectum Diagnostics, and reports grants and non-financial support from Gilead Sciences, and non-financial support from AbbVie and Quadri Pharma, outside the submitted work. RF reports grants, personal fees, and non-financial support from Roche and Gilead Sciences, and personal fees and non-financial support from BMS, outside the submitted work. GBG reports grants and personal fees from Gilead Sciences, outside the submitted work. JG-S reports grants and personal fees from Gilead Sciences, and personal fees from MSD, Abbvie, Janssen, and BMS, outside the submitted work. JGer reports grants and personal fees from AbbVie, Gilead Sciences, Janssen, MSD, BMS, and ViiV Healthcare, outside the submitted work. RG reports grants from New South Wales Ministry of Health and provided project advice regarding viral hepatitis treatment to Gilead Sciences, outside the submitted work. AHa reports unrestricted grants from AbbVie, MSD, Gilead Sciences, BMS, and Novartis, and non-financial support from Gilead Sciences, outside the submitted work; he was also on advisory boards for AbbVie, Gilead Sciences, and BMS. CH reports personal fees from AbbVie, BMS, Gilead Sciences, Janssen, and MSD, outside the submitted work. JJ reports personal fees and non-financial support from Gilead Sciences and AbbVie, and personal fees from Roche and BMS, outside the submitted work. MK reports grants from Roche, Siemens, Hologic, and Boerhinger Ingleheim, outside the submitted work. JVL reports grants and personal fees from Gilead Sciences and personal fees from Cepheid, outside the submitted work. MMan reports personal fees from Roche, BMS, GlaxoSmithKline, Aevi Genomic Medicine, ENYO Pharma, and CureVac, and grants and personal fees from Gilead Sciences and Novartis, outside the submitted work. SMau reports personal fees and non-financial support from Gilead Sciences and BMS, outside the submitted work. CM reports grants and personal fees from AbbVie, Gilead Sciences, and BMS; personal fees from MSD; and grants from Roche, outside the submitted work. BM reports grants and personal fees from Gilead Sciences and personal fees from AbbVie, MSD, BMS, Bayer, Intercept, and Sigma-Tau, during the conduct of the study. FN reports personal fees and non-financial support from Gilead Sciences, during the conduct of the study. AR reports grants and personal fees from AbbVie, Gilead, and MSD, and personal fees form BMS, Celgene, Janssen, Intercept, and Lupin, outside the submitted work. HWR reports grants and personal fees from AbbVie, BMS, Boehringer Ingelheim, ENYO Pharma, Gilead Sciences, Janssen, MSD, PRA Health Sciences, Regulus, and Roche; personal fees from Alnylam and R-Pharm; and grants from Replicor, outside the submitted work. LRR reports grants from the Center for Clinical and Translational Science and the Swedish Research Council (Ghana), during the conduct of the study. LRR also reports grants from Gilead Sciences, BTG, Ariad, and Wako, outside the submitted work, and was a consultant and advisory board member for Wako, Medscape, Axis, OncLive, Bayer, Tavec, and Grail. SDR has served as an advisory board member and speaker for Gilead Sciences, AbbVie, and MSD. OS has served as a consultant and on advisory boards for MSD; received research grants from AbbVie, BMS, MSD, Boehringer Ingelheim, R-Pharm, and Hepatera; and served as a speaker for Abbott, AbbVie, BMS, Gilead Sciences, Janssen, MSD, and R-Pharm. JFS-A reports personal fees from AbbVie and grants from Gilead Sciences and Janssen, outside the submitted work. CSa reports personal fees from Gilead Sciences and BMS, outside the submitted work. PS reports grants and personal fees from Gilead Sciences, AbbVie, and BMS, and personal fees from Intercept, outside the submitted work. CSt has consulted with and served on advisory boards for Gilead Sciences, AbbVie, and MSD. VSy reports grants and personal fees from Gilead Sciences, personal fees and non-financial support from AbbVie, and personal fees from Janssen, outside the submitted work. KT reports grants and personal fees from AbbVie, Gilead Sciences, and BMS; personal fees from MSD and Alfa Wasserman; and grants from Janssen, outside the submitted work. AJvdM reports grants and personal fees from Gilead Sciences and personal fees from AbbVie, outside the submitted work. IW reports personal fees from AbbVie, Gilead Sciences, Janssen, Marcyrl, Mylan, Onxio, and Pharco, outside the submitted work. NW reports personal fees paid to her department from AbbVie, BMS, Gilead Sciences, and MSD, outside the submitted work. VWW reports personal fees from Gilead Sciences, BMS, and MSD, outside the submitted work. M-FY was a speaker or advisory board member for AbbVie, BMS, Gilead Sciences, Roche, GlaxoSmithKline, Fujirebio, Biocartis, and MSD, outside the submitted work. SZ reports consultancy and lecture fees from AbbVie, Gilead Sciences, and MSD, and consultancy fees from Intercept, outside the submitted work. All other authors declare no competing interests., This study was funded by the John C Martin Foundation through the Polaris Observatory. We thank the Research on Hepatitis group (H28-kansei-ippan-001 and H25-kanen-ippan-010; led by JT), funded by the Ministry of Health, Labour and Welfare of Japan, for their provision of country-level data for Japan, and Örebro County Council for providing ALF grants (OLL-683801) to A-SD, which allowed collection of country-level data for Sweden.

Catalyzed by the concerns over the growing public health and economic burden of Hepatitis C virus (HCV) in Switzerland, a diverse group of experts and patient representatives came together in 2014 to develop the Swiss Hepatitis Strategy, setting targets for the elimination of viral hepatitis in Switzerland by 2030. Previous studies have reported the estimated number of chronic HCV infections and forecasted burden of disease given different intervention strategies. However, given new prevalence data by the Swiss Federal Office of Public Health, which decreased total infections by about half, an updated analysis is warranted. We aimed to provide an updated viremic prevalence estimate for Switzerland and evaluate the impact on forecasted liver related morbidity and mortality of an 'inaction' scenario and intervention scenarios to achieve the Global Health Sector Strategy for Viral Hepatitis and Swiss Hepatitis Strategy goals by 2030. A Markov disease-progression model was used to calculate the present and future burden of HCV infection by disease stage according to these different strategies. In 2017, there were an estimated 36,800 (95% UI: 26,900-39,200) viremic infections in Switzerland. Given the current standard of care, total viremic infections are expected to decline by 45%, while cases of decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths will decrease by 20%. If treatment and diagnosis efforts were to cease in 2018, late stage HCV-related morbidity and mortality would increase by 90-100% by 2030. Increasing treatment and diagnosis to achieve the Global Health Sector Strategy or Swiss Hepatitis Strategy goals by 2030, will reduce the number of chronic infections to less than 13,000 and 4,000, respectively. Although the HCV epidemic is declining in Switzerland, efforts to expand diagnosis and treatment are needed to achieve elimination by 2030.

Background Elimination of hepatitis C virus (HCV) among people who inject drugs (PWID) is a costly investment, so strategies should not only focus on eliminating the disease, but also on preventing disease resurgence. The aims of this study are to compute the minimum necessary antiviral therapies to achieve elimination with and without the additional expansion of harm reduction (HR) programs and to examine the sustainability of HCV elimination after 2030 if treatment is discontinued. Method We considered two types of epidemic (with low (30%) and high (50%) proportion of PWID who engage in sharing equipment (sharers)) within three baseline chronic HCV (CHC) prevalence settings (30%, 45% and 60%), assuming a baseline HR coverage of 40%. We define sustainable elimination strategies, those that could maintain eliminations results for a decade (2031–2040), in the absence of additional treatment. Results The model shows that the optimum elimination strategy is dependent on risk sharing behavior of the examined population. The necessary annual treatment coverage to achieve HCV elimination under 45% baseline CHC prevalence, without the simultaneous expansion of HR programs, ranges between 4.7–5.1%. Similarly, under 60% baseline CHC prevalence the needed treatment coverage varies from 9.0–10.5%. Increasing HR coverage from 40% to 75%, reduces the required treatment coverage by 6.5–9.8% and 11.0–15.0% under 45% or 60% CHC prevalence, respectively. In settings with ≤45% baseline CHC prevalence, expanding HR to 75% could prevent the disease from rebounding after elimination, irrespective of the type of the epidemic. In high chronic HCV prevalence, counseling interventions to reduce sharing are also needed to maintain the HCV incident cases in low levels. Conclusions Harm reduction strategies have a vital role in HCV elimination strategy, as they reduce the required number of treatments to eliminate HCV and they provide sustainability after the elimination. The above underlines that HCV elimination strategies should be built upon the existing HR services, and argue for HR expansion in countries without services.

OBJECTIVE. Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use. The objectives were to model the HCV epidemic in Sweden, the burden of disease, and the potential impact of different treatment strategies.HCV disease progression was modeled to 2030. Scenarios were simulated using new DAAs with sustained annual treatment rate (n = 1130), reduced treatment rate (n = 380) to maintain budget, and increased treatment rates (n = 1430 or 2260) to reduce HCV infections.With today's triple therapies, the estimated number of serious liver complications and death are expected to peak in 2021. Using new DAAs among F0-F4 patients, an unchanged annual treatment rate can reduce the number of HCV infections by 10% by 2030; however, hepatocellular carcinoma (HCC) and mortality will remain unchanged. By reducing to 380 treatments annually and focusing on patients with advanced fibrosis (F3-F4), serious complications will remain constant but the total number of HCV infections will increase. By doubling the number of DAA treatments, HCC-incidence and liver-related deaths would decrease by 65-70% by 2030.Mortality and HCC can be reduced with new DAAs and sustained treatment uptake when restricted to F2-F4 patients, or with increased uptake in F0-F4 patients. Treatment restrictions to limit cost may reduce the positive effects and increase the burden of HCV infection. These results may be important for the future strategies of HCV management.

WOS: 000426979400014, PubMed ID: 28404132, Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of-and expansion on-the 2014 analysis, which reported 80 million (95% CI 64-103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1.0% (95% uncertainty interval 0.8-1.1) in 2015, corresponding to 71.1 million (62.5-79.4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections., John C Martin Foundation, John C Martin Foundation.

Summary The treatment of chronic hepatitis C virus (HCV) infection has the potential to change significantly over the next few years as therapeutic regimens are rapidly evolving. However, the burden of chronic infection has not been quantified at the global level using the most recent data. Updated estimates of HCV prevalence, viremia and genotypes are critical for developing strategies to manage or eliminate HCV infection. To achieve this, a comprehensive literature search was conducted for anti-HCV prevalence, viraemic prevalence and genotypes for all countries. Studies were included based on how well they could be extrapolated to the general population, sample size and the age of the study. Available country estimates were used to develop regional and global estimates. Eighty-seven countries reported anti-HCV prevalence, while HCV viraemic rates were available for fifty-four countries. Total global viraemic HCV infections were estimated at 80 (64–103) million infections. Genotype distribution was available for ninety-eight countries. Globally, genotype 1 (G1) was the most common (46%), followed by G3 (22%), G2 (13%), and G4 (13%). In conclusion, the total number of HCV infections reported here are lower than previous estimates. The exclusion of data from earlier studies conducted at the peak of the HCV epidemic, along with adjustments for reduced prevalence among children, are likely contributors. The results highlight the need for more robust surveillance studies to quantify the HCV disease burden more accurately. 2014 European Association for the Study of the Liver. Published by Elsevier B.V.