Recommendations for the Management of Hepatitis C Virus Infection Among People Who Inject Drugs

In the developed world, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). The burden of HCV-related liver disease in this group is increasing, but treatment uptake among PWID remains low. Among PWID, there are a number of barriers to care that should be considered and systematically addressed, but these barriers should not exclude PWID from HCV treatment. Furthermore, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provides a framework for HCV assessment, management, and treatment. Further research is needed to evaluate strategies to enhance assessment, adherence, and SVR among PWID, particularly as new treatments for HCV infection become availabl

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Harm reduction and viral hepatitis C in European prisons: a cross-sectional survey of 25 countries

BACKGROUND: Current estimates suggest that 15% of all prisoners worldwide are chronically infected with the hepatitis C virus (HCV), and this number is even higher in regions with high rates of injecting drug use. Although harm reduction services such as opioid substitution therapy (OST) and needle and syringe programs (NSPs) are effective in preventing the further spread of HCV and HIV, the extent to which these are available in prisons varies significantly across countries. METHODS: The Hep-CORE study surveyed liver patient groups from 25 European countries in 2016 and mid-2017 on national policies related to harm reduction, testing/screening, and treatment for HCV in prison settings. Results from the cross-sectional survey were compared to the data from available reports and the peer-reviewed literature to determine the overall degree to which European countries implement evidence-based HCV recommendations in prison settings. RESULTS: Patient groups in nine countries (36%) identified prisoners as a high-risk population target for HCV testing/screening. Twenty-one countries (84%) provide HCV treatment in prisons. However, the extent of coverage of these treatment programs varies widely. Two countries (8%) have NSPs officially available in prisons in all parts of the country. Eleven countries (44%) provide OST in prisons in all parts of the country without additional requirements. CONCLUSION: Despite the existence of evidence-based recommendations, infectious disease prevention measures such as harm reduction programs are inadequate in European prison settings. Harm reduction, HCV testing/screening, and treatment should be scaled up in prison settings in order to progress towards eliminating HCV as a public health threat

Eliminating viral hepatitis C in Belgium: the micro-elimination approach

Background: Hepatitis C virus is one of the leading causes of chronic liver disease and liver-related deaths worldwide. The estimated prevalence of chronic hepatitis C viral infection among the general Belgian population was 0.57% (n = 64,000) in 2015. Although Belgium has had a ‘Hepatitis C Plan’ since 2014, elimination efforts are unclear. This study employs the best available data and modelling estimates to define the burden of hepatitis C viral infection among key subgroups in Belgium, identify information gaps and propose potential approaches to screening, linkage to care and treatment, and cure. Methods: We examined the peer-reviewed and grey literature since 2012 for data on the prevalence of hepatitis C viral infection in Belgium in key subgroups identified by national experts and in the literature. Ultimately, this research is primarily based on data provided by the key stakeholders themselves due to a lack of reliable data in the literature. Based on this, we modelled the treatment rates required to reach elimination of hepatitis C in several subgroups. Results: Eleven potential subgroups were identified. There were no data available for two subgroups: generational cohorts and men who have sex with men. In six subgroups, fewer than 3000 people were reported or estimated to have hepatitis C infection. Migrants and people who inject drugs were the most affected subgroups, and children were the least affected subgroup. Only two subgroups are on target to achieve elimination by 2030: patients living with haemophilia and transplant recipients. Conclusions: Removing Belgian treatment reimbursement restrictions in January 2019 was a big step towards eliminating HCV. In addition, increasing surveillance, including with a national registry, treatment prescription by other health-care providers and availability of treatment in local pharmacies are central to improving the current situation and getting on track to reach the 2030 WHO hepatitis C elimination targets in Belgium

Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes

Funding Information: This research and Kasper Thorhauge Christensen was funded by grants from the Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO) (G069214, G0B2317N and 1S38819N). Lize Cuypers acknowledges FWO travel grant for a research visit at the University of Oxford (V431117N). Core funding to the Wellcome Centre for Human Genetics was provided by the Wellcome Trust (award 203141/Z/16/Z). The authors acknowledge the STOP-HCV consortium that was funded by a grant from the Medical Research Council, United Kingdom (MR/K01532X/1). Publisher Copyright: © 2023 by the authors.The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium.publishersversionpublishe

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe"

Background &amp; Aims: Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. Methods: We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. Results: At baseline, chronic HCV prevalence varied from &lt;25% (Slovenia/Czech Republic) to &gt;55% (Finland/Sweden), and &lt;2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38–63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12–24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18–79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5–17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20–80%. Conclusions: The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. Lay summary: Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).</p

Adherence to response-guided pegylated interferon and ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: the ACTIVATE study

Background: The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection. Methods: ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment). Results: Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed > 1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8). Conclusions: This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy

Study protocol of KLIMOP: a cohort study on the wellbeing of older cancer patients in Belgium and the Netherlands

<p>Abstract</p> <p>Background</p> <p>Cancer is mainly a disease of older patients. In older cancer patients, additional endpoints such as quality of survival and daily functioning might be considered equally relevant as overall or disease free survival. However, these factors have been understudied using prospective designs focussing on older cancer patients. Therefore, this study will focus on the impact of cancer, ageing, and their interaction on the long-term wellbeing of older cancer patients.</p> <p>Methods/Design</p> <p>This study is an observational cohort study. We aim to recruit 720 cancer patients above 70 years with a new diagnosis of breast, prostate, lung or gastrointestinal cancer and two control groups: one control group of 720 patients above 70 years without a previous diagnosis of cancer and one control group of 720 cancer patients between 50 - 69 years newly diagnosed with breast, prostate, lung or gastrointestinal cancer. Data collection will take place at inclusion, after six months, after one year and every subsequent year until death or end of the study. Data will be collected through personal interviews (consisting of socio-demographic information, general health information, a comprehensive geriatric assessment, quality of life, health locus of control and a loneliness scale), a handgrip test, assessment of medical records, two buccal swabs and a blood sample from cancer patients (at baseline). As an annex study, caregivers of the participants will be recruited as well. Data collection for caregivers will consist of a self-administered questionnaire examining depression, coping, and burden.</p> <p>Discussion</p> <p>This extensive data collection will increase insight on how wellbeing of older cancer patients is affected by cancer (diagnosis and treatment), ageing, and their interaction. Results may provide new insights, which might contribute to the improvement of care for older cancer patients.</p

Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs

Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates &gt;95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.</p