WHO Hepatitis C Virus Elimination Research Articles

Quality Assurance for Hepatitis C Virus Point-of-Care Diagnostics in Sub-Saharan Africa

As part of a multinational study to evaluate the Bioline Hepatitis C virus (HCV) point-of-care (POC) testing in sub-Saharan Africa (SSA), this narrative review summarises regulatory standards and quality indicators for validating and approving HCV clinical diagnostics. In addition, this review also provides a summary of their diagnostic evaluations using the REASSURED criteria as the benchmark and its implications on the WHO HCV elimination goals 2030.

Confirmation of guideline-defined hepatitis C screening strategies within the 'Check-Up35+' examination in the primary care setting.

Screening strategies for undiagnosed infections are fundamental for hepatitis C virus (HCV) elimination. We previously investigated HCV prevalence and screening strategies in an urban primary care setting. IV drug abuse, blood transfusion before 1992, immigration, or elevated ALT were identified as risk factors in a post hoc analysis and diagnosed 83% of unknown HCV-RNA-positive cases by screening only 26% of the population. We aimed to validate prospectively the proposed screening algorithm in two independent urban and rural cohorts and to analyse for potential differences. Anti-HCV and ALT were included in a routine check-up together with a questionnaire covering risk factors. HCV-RNA was analysed in anti-HCV-positive individuals. In urban and rural areas, 4323 and 9321 individuals were recruited. The anti-HCV prevalence was 0.56% and 0.49%, and 0.1% of patients were HCV-RNA-positive in both regions. Fifty-two anti-HCV positive patients including eight HCV-RNA-positive cases were unaware of the infection (number needed to screen to detect one unknown anti-HCV-positive individual: 262). At least one of the three aforementioned risk factors or elevated serum ALT was present in 3000 patients (22%). Restricting HCV screening to only those with risk factors, 52% and 75% of all anti-HCV and HCV-RNA-positive undiagnosed patients were identified (number needed to screen: 111). We confirm prospectively the efficiency of a risk-based HCV screening. The risk-based algorithm should be evaluated in other countries with similarly low HCV prevalence as in Germany to achieve WHO HCV elimination goals.

Systematic Review of Hepatitis C Virus Prevalence in the WHO Western Pacific Region.

Background: This review aimed to identify hepatitis C virus (HCV) prevalence estimates among the general population and six key populations (people who inject drugs, men who have sex with men, sex workers, prisoners/detainees, Indigenous people, and migrants) in the World Health Organization Western Pacific Region (WHO WPR). Methods: Original research articles published between 2016 and 2020 were identified from bibliographic databases. Publications were retrieved, replicas removed, and abstracts screened. Retained full texts were assessed and excluded if inclusion criteria were not met. Methodological quality was assessed using the Johanna Briggs Institute critical appraisal checklist for prevalence data. Data on HCV exposure and active infection were extracted and aggregated and forest plots generated for each population by country. Results: There were no HCV prevalence estimates in any population for more than half of WPR countries and territories. Among the 76 estimates, 97% presented prevalence of exposure and 33% prevalence of active infection. General population viraemic prevalence was 1% or less, except in Mongolia. Results confirm the endemic nature of HCV among people who inject drugs, with estimates of exposure ranging from 30% in Cambodia to 76% in Hong Kong. Conclusions: Countries require detailed knowledge of HCV prevalence in diverse populations to evaluate the impact of efforts to support WHO HCV elimination goals. Results provide baseline estimates from which to monitor and evaluate progress and by which to benchmark future elimination efforts.

The Copenhagen test and treat hepatitis C in a mobile clinic study: a protocol for an intervention study to enhance the HCV cascade of care for people who inject drugs (T’N’T HepC)

IntroductionInjecting drug use is the primary driver of hepatitis C virus (HCV) infection in Europe. Despite the need for more engagement with care, people who inject drugs (PWID) are hard...

Technical Validation of a Hepatitis C Virus Whole Genome Sequencing Assay for Detection of Genotype and Antiviral Resistance in the Clinical Pathway.

Choice of direct acting antiviral (DAA) therapy for Hepatitis C Virus (HCV) in the United Kingdom and similar settings usually requires knowledge of the genotype and, in some cases, antiviral resistance (AVR) profile of the infecting virus. To determine these, most laboratories currently use Sanger technology, but next-generation sequencing (NGS) offers potential advantages in throughput and accuracy. However, NGS poses unique technical challenges, which require idiosyncratic development and technical validation approaches. This applies particularly to virology, where sequence diversity is high and the amount of starting genetic material is low, making it difficult to distinguish real data from artifacts. We describe the development and technical validation of a sequence capture-based HCV whole genome sequencing (WGS) assay to determine viral genotype and AVR profile. We use clinical samples of known subtypes and viral loads, and simulated FASTQ datasets to validate the analytical performances of both the wet laboratory and bioinformatic pipeline procedures. We show high concordance of the WGS assay compared to current “gold standard” Sanger assays. Specificity was 92.3 and 96.1% for AVR and genotyping, respectively. Discordances were due to the inability of Sanger assays to assign the correct subtype or accurately call mixed drug-resistant variants. We show high repeatability and reproducibility with >99.8% sequence similarity between sequence runs as well as high precision for variant frequency detection at >98.8% in the 95th percentile. Post-sequencing bioinformatics quality control workflows allow the accurate distinction between mixed infections, cross-contaminants and recombinant viruses at a threshold of >5% for the minority population. The sequence capture-based HCV WGS assay is more accurate than legacy AVR and genotyping assays. The assay has now been implemented in the clinical pathway of England’s National Health Service HCV treatment programs, representing the first validated HCV WGS pipeline in clinical service. The data generated will additionally provide granular national-level genomic information for public health policy making and support the WHO HCV elimination strategy.

Estimating the Consensus hepatitis C Cascade of Care among people who inject drugs in Australia: Pre and post availability of direct acting antiviral therapy

Background Monitoring the hepatitis C virus (HCV) cascade of care (CoC) among people who inject drugs (PWID) is an essential component of the response to World Health Organisation's (WHO) hepatitis elimination goals. This study aimed to estimate the Consensus hepatitis C CoC among PWID using data collected in Australia prior to and after the introduction of unrestricted direct-acting antiviral (DAA) therapy in March 2016.Methods The Australian Needle Syringe Program Survey is a cross-sectional bio-behavioural surveillance system that recruits >2000 PWID annually. Using data from 2015 and 2019, HCV antibody and ribonucleic acid (RNA) test results from dried blood spots were combined with self-reported data on HCV diagnostic testing and treatment to project HCV Consensus CoC indicators at a population-level among Australian PWID.Results Among an estimated 75,000 people who inject drugs on a regular basis in Australia, the number with active HCV infection declined from 32,619 (44%) in October 2015 to 12,679 (17%) in October 2019. The majority (78% in 2015 and 2019) of PWID reported HCV diagnosis, while the proportion of those diagnosed who were treated increased from 3% in 2015 to 47% in 2019. Among those treated, the proportion who were HCV RNA negative and assumed to have been successfully treated (cured), increased from 27% in 2015 to 88% in 2019.Conclusion This study demonstrates remarkable HCV CoC progress among PWID in Australia following availability of DAA therapy. There was a substantial increase in the proportion of HCV diagnosed PWID who initiated treatment and were cured, while the number of PWID with active HCV infection more than halved over a 3.5 year period. Estimates of the Consensus hepatitis C CoC among PWID is required to monitor progress toward WHO HCV elimination goals.

Interventions to reduce acute hepatitis C virus in HIV-positive MSM.

The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets. With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing. Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.

Can Australia Reach the World Health Organization Hepatitis C Elimination Goal by 2025 Among Human Immunodeficiency Virus-positive Gay and Bisexual Men?

Human immunodeficiency virus (HIV)-positive gay and bisexual men (GBM) in Australia are well engaged in care. The World Health Organization's (WHO) hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population. We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use. HCV incidence in our model increased from 0.7 per 100 person-years in 2000 to 2.5 per 100 person-years in 2016 and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65% per year between 2016 and 2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person-years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person-years (76% decline). If the proportion of eligible patients using DAAs dropped from 65% per year in 2016 to 20% per year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person-years (70% reduction). Reaching the WHO HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable.

Australia on track to achieve WHO HCV elimination targets following rapid initial DAA treatment uptake: A modelling study.

Subsidized direct-acting antiviral (DAA) treatment recently became available to all adults living with chronic hepatitis C virus (HCV) in Australia. Based on rapid uptake (32600 people initiated DAA in 2016), we estimated the impact on HCV epidemiology and mortality in Australia and determined if Australia can meet the WHO HCV elimination targets by 2030. Using a mathematical model, we simulated pessimistic, intermediate and optimistic DAA treatment scenarios in Australia over 2016-2030. We assumed treatment and testing rates were initially higher for advanced fibrosis and the same across HCV transmission risk level sub-populations. We also assumed constant testing rates after 2016. We compared the results to the 2015 level and a counterfactual (IFN-based) scenario. During 2016-2030, we estimated an intermediate DAA treatment scenario (2016, 32600 treated; 2017, 21370 treated; 201817100 treated; 2019 and beyond, 13680 treated each year) would avert 40420 new HCV infections, 13260 liver-related deaths (15320 in viraemic; -2060 in cured) and 10730 HCC cases, equating to a 53%, 63% and 75% reduction, respectively, compared to the IFN-based scenario. The model also estimated that Australia will meet the WHO targets of incidence and treatment by 2028. Time to a 65% reduction in liver-related mortality varied considerably between HCV viraemic only cases (2026) and all cases (2047). Based on a feasible DAA treatment scenario incorporating declining uptake, Australia should meet key WHO HCV elimination targets in 10 to15years. The pre-DAA escalation in those with advanced liver disease makes the achievement of the liver-related mortality target difficult.

Evaluating “treatment as prevention” on the road to hepatitis C virus elimination

Fraser and colleagues (1) have recently published the results of a study modelling the direct acting antiviral (DAA) scale-up requirements needed to reduce hepatitis C virus (HCV) infection in people who inject drugs (PWID) within selected European sites. Such “treatment as prevention” strategies have been previously proposed to address the ambitious WHO HCV elimination target for 2030 (2), established in response to the world-wide exponential growth in HCV-associated liver disease which has occurred in the past few decades and is a leading cause of increased liver-related mortality (3).

PRM131 - HEPATITIS C VIRUS ELIMINATION AND ERADICATION MODELS: A SYSTEMATIC LITERATURE REVIEW

Hepatitis C virus (HCV) elimination is an achievable goal due to highly effective direct-acting antiviral (DAA) therapies. Between 2015-2030, WHO targets globally 1) reduction in new HCV infections by 80%; 2) reduction in HCV deaths by 65%; 3) increase in HCV diagnoses from <5% to 90%; 4) increase in HCV treatment among eligible persons from <1% to 80%. The aim of this study was to systematically review the modeling approaches and results of full-economic evaluations targeting the elimination or eradication of HCV in any geographical setting. By using Scopus and OVID databases a systematic review of English-language articles published between January 2010 and October 2017 was performed, as the appearance of DAAs made the elimination or eradication of HCV a realistic goal after 2010. Data on country setting, modeling approach and results of the observed scenarios were extracted. A total of 504 articles were identified. After title/abstract and full text screening 4 studies were included into the review. These studies used dynamic economic models, compared at least four scenarios, and reported data on the treated patient numbers, total cost of the scenarios, prevalence and/or incidence reduction of HCV and mortality reduction in percentage or absolute numbers. Three of the included studies employed backward calculation to recommend strategies to reach at least one WHO HCV elimination target, the fourth study examined the impact of specific scenarios on HCV elimination and did not consider the WHO targets. Only a limited number of economic analyses were carried out to investigate the consequences of the elimination or eradication of HCV. Our findings suggest that high utilization rate of DAA therapies could help to eradicate HCV infection. However, even with unlimited number of treatment courses, interventions to improve the diagnostics and cascade of care are also required to achieve WHO HCV elimination targets.

Hepatitis C in Laos: A 7-Year Retrospective Study on 1765 Patients.

Hepatitis C virus (HCV) is a global health concern, notably in Southeast Asia, and in Laos the presentation of the HCV-induced liver disease is poorly known. Our objective was thus to describe a comprehensive HCV infection pattern in order to guide national health policies. A study on a group of 1765 patients formerly diagnosed by rapid test in health centres was conducted at the Centre of Infectiology Lao Christophe Merieux in Vientiane. The demographic information of patients, their infection status (viral load: VL), liver function (aminotransferases) and treatments were analysed. Results showed that gender distribution of infected people was balanced; with median ages of 53.8 for men and 51.6years for women (13-86years). The majority of patients (72%) were confirmed positive (VL > 50IU/mL) and 28% of them had high VL (> 6log10). About 23% of patients had level of aminotransferases indicative of liver damage (> 40IU/mL); but less than 20% of patients received treatment. Patients rarely received a second sampling or medical imaging. The survey also showed that cycloferon, pegylated interferon and ribavirin were the drugs prescribed preferentially by the medical staff, without following any international recommendations schemes. In conclusion, we recommend that a population screening policy and better management of patients should be urgently implemented in the country, respecting official guidelines. However, the cost of biological analysis and treatment are significant barriers that must be removed. Public health resolutions should be immediately enforced in the perspective of meeting the WHO HCV elimination deadline by 2030.

Is hepatitis C virus elimination possible among people living with HIV and what will it take to achieve it?

IntroductionThe World Health Organization targets for hepatitis C virus (HCV) elimination include a 90% reduction in new infections by 2030. Our objective is to review the modelling evidence and cost data surrounding feasibility of HCV elimination among people living with HIV (PLWH), and identify likely components for elimination. We also discuss the real‐world experience of HCV direct acting antiviral (DAA) scale‐up and elimination efforts in the Netherlands.MethodsWe review modelling evidence of what intervention scale‐up is required to achieve WHO HCV elimination targets among HIV‐infected (HIV+) people who inject drugs (PWID) and men who have sex with men (MSM), review cost‐effectiveness of HCV therapy among PLWH and discuss economic implications of elimination. We additionally use the real‐world experience of DAA scale‐up in the Netherlands to illustrate the promise and potential challenges of HCV elimination strategies in MSM. Finally, we summarize key components of the HCV elimination response among PWLH.Results and discussionModelling indicates HCV elimination among HIV+ MSM and PWID is potentially achievable but requires combination treatment and either harm reduction or behavioural risk reductions. Preliminary modelling indicates elimination among HIV+ PWID will require elimination efforts among PWID more broadly. Treatment for PLWH and high‐risk populations (PWID and MSM) is cost‐effective in high‐income countries, but costs of DAAs remain a barrier to scale‐up worldwide despite the potential low production price ($50 per 12 week course). In the Netherlands, universal DAA availability led to rapid uptake among HIV+ MSM in 2015/16, and a 50% reduction in acute HCV incidence among HIV+ MSM from 2014 to 2016 was observed. In addition to HCV treatment, elimination among PLWH globally also likely requires regular HCV testing, development of low‐cost accurate HCV diagnostics, reduced costs of DAA therapy, broad treatment access without restrictions, close monitoring for HCV reinfection and retreatment, and harm reduction and/or behavioural interventions.ConclusionsAchieving WHO HCV Elimination targets is potentially achievable among HIV‐infected populations. Among HIV+ PWID, it likely requires HCV treatment scale‐up combined with harm reduction for both HIV+ and HIV‐ populations. Among HIV+ MSM, elimination likely requires both HCV treatment and behaviour risk reduction among the HIV+ MSM population, the latter of which to date has not been observed. Lower HCV diagnostic and treatment costs will be key to ensuring scale‐up of HCV testing and treatment without restriction, enabling elimination.