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Achieving hepatitis C elimination in Europe -
To treatment scale-up and beyond - Editorial
  Download the PDF here
Download the PDF here
[Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe]
Dec 7 2017 - Jnl of Hepatology - M. Hellard1,2,3,, N. Scott1,2, R. Sacks-Davis1,4, A. Pedrana1,2
1Burnet Institute, Melbourne, VIC 3004, Australia; 2Department of Epidemiology and Preventive Medicine, Monash University, Clayton, VIC
3008, Australia; 3Department of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, VIC 3004,
Australia; 4Department of Medicine, University of Melbourne, Parkville, VIC 3010
Fraser and colleagues1 have used a mathematical model to show that for many European countries, using direct-acting antiviral (DAA) therapy to treat hepatitis C infection is unlikely to have a substantive impact on hepatitis C incidence and prevalence among people who inject drugs (PWID) unless treatment rates are increased substantively beyond current levels. Their model explicitly accounts for the opioid substitution therapy (OST) and needle and syringe program (NSP) coverage of each setting, which is important not only because of the proven effectiveness of the programs in reducing hepatitis C transmission,2 but because it allows the authors to quantify the benefits of prevention interventions in isolation and when combined with treatment scale-up. Their findings reiterate the importance of high prevention coverage (OST and NSP) as a primary method of reducing incidence and prevalence and also as a method of enhancing the epidemiological impact of treatment, through treatment-as-prevention.
The implication of this work is that for many countries the elimination of hepatitis C as a public health threat is not going to happen by chance. A number of barriers need to be overcome, requiring a focused effort from governments and health services. The first barrier is that widespread treatment scale-up is currently precluded by restricted and inconsistent access policies in many European countries.[3], [4] Fraser and colleagues' model predicts that without scaling up universal treatment access, OST and NSP alone can produce notable decreases in hepatitis C prevalence, from approximately 20% to more than 75%, depending on current coverage. However, the greatest and most rapid benefits require a combination of both prevention and treatment scale-up in unison.
Despite the current barriers to treatment access in some countries, continued falling prices and growing evidence for the cost-benefit of elimination efforts means that treatment access is constantly changing. It is difficult to imagine that universal treatment access will not become a reality for these countries eventually. Therefore, while the continued advocacy for unrestricted treatment access continues to be of immediate importance, it should not be allowed to distract from the many other aspects of a comprehensive programmatic response that are required to achieve hepatitis C elimination - activities which represent equally critical pieces of the elimination puzzle.
A second and potentially more complex barrier to treatment scale-up is countries' capacities and health infrastructures to deliver treatment and prevention programs at scale. If Fraser and colleagues' model predictions are correct - that elimination is theoretically achievable by scaling up prevention and treatment -broader questions must now be asked of these settings. How will countries scale up access to treatment, and what additional health system strengthening activities would be required if unrestricted access were granted tomorrow? These activities include training and education for providers, increasing laboratory capacity to ensure appropriate testing and increasing awareness of DAAs among key risk populations. In addition, could these changes to the health system be started now in anticipation of drug prices that will inevitably decrease? Mathematical models suggest that the extent and speed at which treatments are scaled-up are important determinants of reinfection and cumulative treatment costs. Lessons learnt from implementation science must therefore be incorporated into broader hepatitis C strategies. In settings with unrestricted access, such as Australia, evidence is emerging that the additional activities required to achieve and sustain high treatment rates require substantial time and effort to coordinate. This includes addressing staffing capacity constraints, diversifying and decentralising services, addressing stigmatization and discrimination and ensuring geographically and culturally appropriate services are available.[5], [6]
Health system limitations form an upper bound on the possible treatment scale-up, since existing services may not have the resources or workforce capacities to support substantive increases in patient numbers. A third barrier to scale-up is effectively engaging key risk populations and their specific needs.7 Implicit in Fraser and colleagues' study is the well-established message that to achieve hepatitis C elimination in most European countries treatment scale-up needs to happen among PWID, the group at greatest risk of transmission, otherwise treatment-as-prevention will not be effective. However, decades of conservative drug policy in most European countries, leading to stigmatization and discrimination, among other factors, have resulted in low engagement of PWID in care in many communities.[8], [9], [10] This must be addressed, since improvements in all aspects of the care cascade,11 including increased testing frequency well beyond current practice,12 are required to achieve and sustain high treatment uptake among PWID. The establishment of flexible and culturally acceptable models of care for patients, in particular PWID, has been shown to improve both capacity and engagement. The simplicity of treatments means they can be administered in primary healthcare settings, rather than confined, as in the era of pegylated interferon and ribavirin, to hospital settings. There is increasing evidence that community-based treatment approaches are highly effective in engaging PWID in care and treatment.[13], [14] In Australia, a policy enabling non-specialist prescribing of hepatitis C treatments has been in place since DAAs became available in 2016. As a result, over the first 14 months 46% of treatments were prescribed by non-specialists,13 with particularly high rates of non-specialist prescribing among indigenous, immigrant and regional communities. This policy also facilitates the use of peer-led15 and nurse-led models of care,16 which are able to use community-based services[17], [18] as primary contact points for diagnosis and treatment.
Fraser and colleagues also touch on the importance of robust surveillance systems for monitoring and evaluating any hepatitis response. In addition to the capacity to monitor chronic HCV prevalence and treatment rates among PWID, these systems will need to monitor newly acquired infection, including reinfection after treatment.19 These systems are also critical to ensure services are appropriately located. For example, transmission occurring through injecting drug use is geographically heterogeneous and related to drug market characteristics, yet while health services are also often geographically heterogeneous, they are often distributed according to different coverage objectives. Therefore, it is important that effective resource planning is undertaken to ensure appropriate hepatitis C-related services are located in areas of greatest demand and where unmet need is greatest. This should be guided by evidence and appropriate data, and again, it requires time and planning to put suitable systems in place.20
In summary, Fraser et al. demonstrate that substantive gains can be made towards hepatitis C elimination in Europe if increases in treatment rates and harm reduction coverage are achieved. Universal access to DAAs is required to achieve the WHO 2030 elimination targets and ultimately this will happen in the region. However, while waiting for this to occur, countries should act now to improve their health services infrastructure and ensure the platforms required are in place to successfully deliver scaled-up DAA treatment in a timely manner when universal access does arrive. A comprehensive elimination program requires more than just DAAs, and depending on the starting point it can take many years to set up sufficient service diversity, infrastructure capacity and surveillance systems to facilitate the increases in testing and retention in care that are required. Lessons should be learnt from other settings on the most effective models of care to maximize treatment uptake.
Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

⋅Chronic HCV prevalence and treatment rates among PWID vary widely across Europe.
⋅HCV treatment scale-up is required in most sites to reduce HCV transmission.
⋅Increasing OST/NSP coverage enhances HCV treatment prevention benefit.
Background & 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.
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.
At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <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%.
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).
Main findings

Treatment scale-up is needed to achieve observable reductions in chronic HCV prevalence among PWID in most sites in Europe, even with new DAAs. Doubling the DAA treatment rates may lead to observable reductions (12-24% decrease) in chronic prevalence by 2026 in Belgium, Denmark, Hamburg, Norway, and Scotland; but not in Finland or Sweden. Exceptions include Czech Republic, Slovenia, and Amsterdam, which, at current HCV treatment rates, are projected to reduce chronic HCV prevalence from a third to a half by 2026. This is because of the low or decreasing prevalence of infection in these settings. Alternatively, increasing OST and NSP coverage to 80% with the current HCV treatment rates would reduce chronic HCV prevalence by 17-20% in Finland and Hamburg, and 30-79% in all other sites. Reducing HCV incidence to <2% by 2026 requires little action in Amsterdam, Czech Republic, and Slovenia, whereas in Belgium, Denmark, Hamburg, Norway, and Scotland it will require at least a fivefold increase in the current HCV treatment rates, or 1.8- to 4.7-fold if OST and NSP are scaled-up to 80% coverage.

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