The elimination of hepatitis C as a public health threat is now possible, with treatment that cures almost everyone. Micro-elimination is a new concept in hepatitis C that involves eliminating hepatitis C for defined segments of the population as a strategy to incrementally achieve national elimination. Micro-elimination is proposed as a pragmatic way to establish realistic elimination goals, allocate resources and support local expertise to tailor, deliver and scale up interventions. Segments of the population that can be targeted for micro-elimination can include people in certain settings, geographic areas, subpopulations and age cohorts, for example people in prisons, people in cities or people with co-infections.1,2 This article will explore the concept of micro-elimination of hepatitis C and share promising results from initiatives and modelling studies.
Eliminating hepatitis C as a public health threat
Canada signed on to the World Health Organization’s global health sector strategy on viral hepatitis, 2016–2021, to eliminate viral hepatitis as a public health threat by 2030.3 The strategy laid out national targets that include diagnosing 90% of people living with hepatitis C, treating 80% of people with hepatitis C who are eligible for treatment and reducing new infections by 90%.4 The strategy also included targets for needle and syringe coverage for people who use injection drugs and called for a package of harm reduction services that include needle and syringe programs, opioid agonist therapy and risk reduction education. When this article refers to the micro-elimination of hepatitis C, the focus is on eliminating hepatitis C as a public health threat by achieving these World Health Organization targets.
Given the high cost of hepatitis C treatment in many countries, including Canada, there can be high upfront costs in achieving national elimination targets, despite the long-term effectiveness and public health benefits of such efforts.5 Micro-elimination of hepatitis C is a strategy to incrementally achieve national elimination through initiatives that eliminate hepatitis C for defined segments of the population, such as within settings, geographic areas, subpopulations and age cohorts.1
This concept is proposed as a pragmatic way to support establishing realistic elimination goals, allocating resources efficiently and using local expertise to tailor, deliver and scale up interventions. Micro-elimination can also build support and generate momentum for national elimination by demonstrating early successes.1
The selection of settings, geographic areas, subpopulations or age cohorts for micro-elimination initiatives should be based on higher risk or burden of hepatitis C. The initiatives should be grounded in a health equity approach that ensures marginalized communities are included in the elimination of hepatitis C.6
A micro-elimination approach
Building on the concept of micro-elimination, key criteria for a micro-elimination approach have been proposed. The criteria encourages evidence-informed decision making, the development and monitoring of targets, and the involvement of and collaboration among the people who are most knowledgeable about specific population groups, including patient groups and groups representing the populations.2 There are four criteria for a micro-elimination approach:
- There must be a plan as to how resources and services will be tailored to overcome known barriers to achieve micro-elimination goals.
- The plan should include realistic annual targets including the treatment and diagnosis levels required to achieve elimination targets.
- The plan should be developed and implemented through a multi-stakeholder process that includes government officials, health service providers and civil society representatives, including people with lived experience.
- Progress and outcomes should be monitored and publicly reported using pre-defined indicators.2
Two additional key concepts in the micro-elimination approach include addressing the gap in the number of people who have hepatitis C and don’t know it by scaling up screening and diagnosis efforts. Further, scaling up treatment access has the primary benefit of curing a person of hepatitis C, and it is also suggested to have a prevention benefit: wide-scale treatment and cure means there are fewer people with hepatitis C, therefore fewer opportunities for onward transmission of the virus and a decrease in the number of new infections. This concept is called Treatment as Prevention.2
Mathematical modelling studies have projected what it would take to eliminate hepatitis C in specific locations and subpopulations. For example, a modelling study estimated that to achieve a 90% reduction in hepatitis C infections by 2030 in the state of Rhode Island, United States, over 2,000 people need to be treated annually by 2020.7 A modelling study on hepatitis C elimination among men who have sex with men in the United Kingdom looked specifically at the concept of Treatment as Prevention and found that rapid scale up of treatment and moderately successful behavioural interventions to prevent new infections could substantially reduce the incidence of hepatitis C among this population.8 Another modelling study focused on Montreal found that substantially scaling up treatment, without restrictions on minimum degree of liver injury, and access to harm reduction services in Montreal could decrease the burden of hepatitis C among people who use injection drugs.9
What does micro-elimination look like in practice?
Examples of research evidence on micro-elimination initiatives will be presented in the remainder of this article. The initiatives are grouped according to whether they target people in certain settings, geographic areas, subpopulations or age cohorts. The initiatives are at various stages of development, ranging from ones that are at the proposal stage to ones that have achieved micro-elimination of hepatitis C. The information available on the programs and their outcome measures varies from case study to case study; where available, outcome data are presented in this article. An analysis of whether the initiatives meet the criteria of a micro-elimination approach is not included.
Micro-elimination in settings
Settings for micro-elimination can include hospitals, addictions services and prisons. Prisons or correctional facilities in particular have been recognized as promising settings. Prison populations have a disproportionately high prevalence of hepatitis C2,10, 11 and these facilities are controlled environments that can facilitate harm reduction support, linkage to care and treatment. Two observational studies have demonstrated success in implementing micro-elimination programs in a prison setting.
A Spanish prison, El Dueso, virtually eliminated hepatitis C through a “test and treat” program and harm reduction services such as a needle and syringe program and opioid agonist therapy. The program offered testing to new and current prisoners, followed by routine testing every six months and upon release from prison. People in prison longer than 30 days were offered treatment through directly observed therapy. During a 14-month observational study (2016– 2017), 99.5% of people in the prison (847 of 851) agreed to participate in the screening program. A total of 86 people were diagnosed with hepatitis C and all 69 people who were offered treatment started treatment (17 people were not offered treatment because they were expected to be in prison for fewer than 30 days). Three people were still on treatment at the time of publication. Among people who had completed treatment, 97% (64 of 66) were cured of hepatitis C (this includes three people who were cured only after a second round of treatment); the remaining two people were lost to follow-up upon their release from prison, therefore cure could not be assessed. The incidence of new hepatitis C infections decreased from 1.7 per 100 person-years to 0 per 100 person-years. There were no cases of hepatitis C re-infection during follow-up.10
The Lotus Glen Correctional Centre in Australia achieved near-elimination of hepatitis C by scaling up testing and treatment services. Routine voluntary testing was offered upon entry to the facility and testing was also provided upon request or recommendation from the nursing staff. People with hepatitis C were offered treatment through directly observed therapy, counselling on preventing re-infection and linkage to care in the community upon release. There were no restrictions on access to treatment, such as length of incarceration. During a 22-month observational study (2016–2017), about 90% of people in this prison received hepatitis C testing. A total of 125 people were assessed and 119 of them started treatment; four people declined treatment and two were transferred to another correctional facility before starting treatment. Sixty-six people completed treatment, 32 were lost to follow-up and 21 were still on treatment or in post-treatment follow-up at the time of publication. Of the 66 people who completed treatment, 97% (64) were cured of hepatitis C. Prevalence rates in the prison decreased from 12% to 1%. There were two cases of re-infection among people at the Lotus Glen Correctional Centre. This highlights the importance of harm reduction and other prevention strategies in addition to scaling up routine testing and treatment.11
Micro-elimination in geographic areas
Micro-elimination initiatives that target the population in a particular geographic area, such as a province or city, can be a pragmatic approach because the relevant policies and resources are often under the authority of a particular geographic jurisdiction. For example, in Canada, healthcare is the responsibility of the provincial and territorial governments, which means that it may make sense to create provincial and territorial elimination plans. The observational studies discussed below have examined province/territory/state-wide and city-wide elimination initiatives.
Prince Edward Island launched a multi-phase hepatitis C elimination strategy in 2015. Program components included expanded testing at targeted services (such as needle and syringe programs, methadone clinics, addictions services and emergency departments), centralized referral and intake, a hepatitis C nurse care coordinator and no restrictions on what degree of liver injury was required for access to treatment. During the first year of the PEI Hepatitis C Treatment Program, referrals for treatment were triaged on the basis of medical necessity and patients’ genotypes (in this case, genotypes 1 and 4). During the first year of the program, 242 referrals were received, 123 patients were seen for intake and 93 people started treatment. This is an increase from four treatment initiations two years earlier. Nine patients were still on treatment or waiting for their results at the time of publication. The cure rate was 98% (82 of 84); one patient was lost to follow up and one patient died from an unrelated cause.12 The success of the program led to plans for expanded access for patients with all genotypes.
A village in Egypt called Al-Othmanya developed an initiative to eliminate hepatitis C among adults (age 12–80 years) in the village through partnerships, awareness raising, health education and free and comprehensive testing, linkage to care and treatment access. Over a one-year period, 89% of eligible villagers (4,215 of 4,721) were screened for hepatitis C. Of those with diagnosed hepatitis C, 96% were treated (300 of 312), and 98% of those who received treatment were cured (293 of 300).13
Other cities or states have recently developed local elimination plans. New York State has developed an elimination program through extensive stakeholder engagement with political and bureaucratic offices, healthcare and support workers and people with lived experience. The plan includes expanding screening and testing for hepatitis C, linking people with hepatitis C to care and providing unrestricted access to hepatitis C treatment and care. No data are available at this time.14 Another example is the city of San Francisco, which has developed an elimination initiative called END HEP C SF, which includes measurable priorities for action such as increasing community-based testing, launching hepatitis C navigation services and increasing access to treatment including within primary care and nonclinical settings. No data are available at this time.14
Micro-elimination in subpopulations and age cohorts
Subpopulations and age cohorts may be chosen as targets for micro-elimination strategies because of a variety of characteristics the group might have, such as high rates of hepatitis C, priorities for treatment because of advanced hepatitis C infection or current engagement with the healthcare system. The following subpopulations have been suggested for consideration: hemodialysis recipients, indigenous communities, children of mothers with hepatitis C, people with an HIV and hepatitis C co-infection, migrants from high-prevalence countries, people who inject drugs, people with hemophilia and other inherited blood disorders, people in prison, transplant recipients and age cohorts with high hepatitis C prevalence.2 Four observational studies have explored initiatives targeting subpopulations and age cohorts.
People already engaged in healthcare for another reason have been identified as a priority for hepatitis C testing and treatment. In Slovenia, data from a national registry identified people with congenital bleeding disorders who tested positive for hepatitis C antibodies during a screening program in the 1990s. Seventy-three people with chronic hepatitis C were identified; however, seven of them died before receiving treatment. Treatment was initiated in all but one patient (65 of 66); this patient had a severe co-morbidity. Two people were completing treatment at the time of publication so complete results were not available. In total, 98% (62 of 63) of the people who had completed treatment were cured of hepatitis C (some had multiple courses of treatment and some had interferon-based treatment); one person died before completing treatment. Through this initiative, micro-elimination within this population was achieved.15
In the Netherlands, the government scaled up hepatitis C treatment in 2015 by providing unrestricted access to direct-acting antivirals (DAAs). An observational study looked at a database in the Netherlands that captures information from over 98% of people diagnosed with HIV who are in care, which includes people with a co-infection with hepatitis C. Between 2000 and 2017, 87% (1,284 of 1,471) of people co-infected with HIV and hepatitis C had ever started hepatitis C treatment, including interferon-based treatment. In total, 94% of patients (1,124 of 1,192) known to have completed their treatment were cured (14 people who took DAAs and 54 people who took interferon-based treatment required re-treatment). At the time of publication, 76% of people co-infected with HIV and hepatitis C (1,124 of 1,471) were cured of hepatitis C and 6% of people (92 of 1,471) were currently on treatment or waiting for their results. This rapid scale up of hepatitis C treatment can contribute significantly to elimination efforts, but the researchers also noted the importance of scaling up harm reduction and testing to achieve elimination targets.16 Unrestricted access to hepatitis C treatment also resulted in a 51% decrease in the incidence of hepatitis C infection among HIV-positive men who have sex with men.17
Since 2014, the Department of Veteran Affairs in the United States has made significant progress in scaling up testing and treatment among veterans. The initiative included establishing Hepatitis C Innovation Teams that led efforts to implement best practices and develop creative solutions to address local barriers to hepatitis C service delivery. The department increased capacity and access in several ways, including the following: it initiated automated outreach to veterans born between 1945 and 1965 for hepatitis C testing, it changed its policies to give clinical pharmacists greater responsibility for managing hepatitis C treatment, it organized group medical visits for uncomplicated patients who were going to take the same treatment regimen and it implemented electronic/virtual consults. By December 2017, 81% of the 2.89 million veterans born between 1945 and 1965 had been screened for hepatitis C. Veterans Affairs has cured almost 60% of people in their care who were diagnosed with hepatitis C (no date available). As of December 2017, fewer than 42,000 veterans were waiting for hepatitis C treatment.18
Cherokee Nation Health Services, an independent health service that is run by the Cherokee Nation, a federally recognized sovereign government of the Cherokee people in the United States, implemented a hepatitis C testing policy in October 2012, initially targeted to people born between 1945 and 1965. This was done through a reminder in the electronic health record of patients. Hepatitis C education was also offered to primary care providers to increase their capacity to manage and treat hepatitis C. From October 2012 to July 2015, testing coverage in people born between 1945 and 1965 increased to nearly 40%, and overall testing increased five-fold. Three hundred and eight-eight people were found to have chronic hepatitis C and 58% (223 of 388) of them started interferon-based or DAA treatment. Of those who started treatment, 90% (201 of 223) completed treatment and 90% (180 of 201) of them were cured. Twenty-one people were lost to follow-up. In October 2015, the Path Toward Elimination of HCV [Hepatitis C] program was launched on the basis of this success. This program involves expanding screening to people aged 20 to 69 years, further increasing clinical capacity to treat hepatitis, and implementing prevention interventions.19
Recommendations for service providers
Micro-elimination can be implemented on a small or broad scale, ranging from one hepatitis C program or setting to a national strategy for a subpopulation. Core components of a micro-elimination program include scaling up prevention, testing, diagnosis, linkage to care and access to treatment. Considerations for a micro-elimination program include the following:
- Sufficient coverage and access to harm reduction services such as needle and syringe programs, opioid agonist therapy and other prevention services need to be provided.
- Expanded screening and diagnosis efforts to address the gap in people who have hepatitis C but do not know it.
- A target group needs to be determined for the program, and the program and resources need to be tailored to meet the needs of that group. The selection of the target groups should be data driven and should be based on a clear rationale, such as a higher risk of hepatitis C in the group or increased barriers to accessing prevention, testing and treatment.
- Stakeholders should be engaged to design the initiative; there should be meaningful involvement of people with lived experience, civil society representatives, health service providers, and government representatives.
- An evaluation plan should be developed that has clear targets to support program development and provide feedback on implementation, impact and opportunities for addressing gaps or barriers within the program.
- a. b. c. Lazarus JV, Wiktor S, Colombo M et al. Micro-elimination – a path to global elimination of hepatitis C. Journal of Hepatology. 2017 Oct;67(4):655-66.
- a. b. c. d. e. f. Lazarus JV, Safreed-Harmon K, Thursz MR. The micro-elimination approach to eliminating hepatitis C: strategic and operational considerations. Seminars in Liver Disease. 2018 Aug;38(3):181-92.
- Government of Canada. A Pan-Canadian Framework for Action: Reducing the Health Impact of Sexually Transmitted and Blood-borne Infections in Canada by 2030. 2018 Jun. Available from: https://www.canada.ca/content/dam/phac-aspc/documents/services/infectious-diseases/sexual-health-sexually-transmitted-infections/reports-publications/sexually-transmitted-blood-borne-infections-action-framework/sexually-transmitted-blood-borne-infections-action-framework.pdf
- World Health Organization. Global Health Sector Strategy on Viral Hepatitis, 2016–2021. 2016 Jun. Available from: http://apps.who.int/iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf?sequence=1
- Cipriano LE, Goldhaber-Fiebert JD. Population health and cost-effectiveness implications of a “Treat All” recommendation for HCV: a review of model-based evidence. MDM Policy & Practice. 2018 May 24;3(1):2381468318776634.
- Lazarus JV, Pericàs JM, Colombo M et al. Viral hepatitis: “E” is for equitable elimination. Journal of Viral Hepatology. 2018 Oct;69(4):762-4.
- Soipe AI, Razavi H, Razavi-Shearer D et al. Chronic hepatitis C virus (HCV) burden in Rhode Island: modelling treatment scale-up and elimination. Epidemiology and Infection. 2016 Dec;144(16):3376-86.
- Martin N K, Thornton A, Hickmen M et al. Can hepatitis C virus (HCV) direct-acting antiviral treatment as prevention reverse the HCV epidemic among men who have sex with men in the United Kingdom? Epidemiological and modeling insights. Clinical Infectious Diseases. 2016 May;62(9):1072-80.
- Cousien A, Leclerc P, Morissette C et al. The need for treatment scale-up to impact HCV transmission in people who inject drugs in Montreal Canada: a modelling study. BMC Infectious Diseases. 2017;17(1):162.
- a. b. Cuadrado A, Llerena S, Cobo C et al. Microenvironment eradication of hepatitis C: a novel treatment paradigm. American Journal of Gastroenterology. 2018 Jun;[Epub ahead of print].
- a. b. Bartlett SR, Fox P, Cabatingan H et al. Demonstration of near-elimination of hepatitis C virus among a prison population: the Lotus Glen Collection Centre Hepatitis C Treatment Project. Clinical Infectious Diseases. 2018;67(3):460-3.
- Francheville JW, Rankin R, Beck J. Early success in an open access, provincially funded hepatitis C treatment program in Prince Edward Island. Annals of Hepatology. 2017;16(5):749-58.
- Shiha G, Metwally AM, Soliman R et al. An education, test, and treat programme towards elimination of hepatitis C infection in Egypt: a community-based demonstration project. Lancet Gastroenterology and Hepatology. 2018 Jun;[Epub ahead of print].
- a. b. Gaudino A, Gay B, Garmon C et al. Localized US efforts to eliminate hepatitis C. Infectious Disease Clinics of North America. 2018;32:293-311.
- Maticic M, Lekse A, Kozinc M et al. Micro-elimination of hepatitis C among patients with congenital bleeding disorders in Slovenia. Journal of Hepatology. 2018 Apr;68(Supplement 1):S193-4.
- Boerekamps A, Newsum AM, Smit C et al. High treatment uptake in human immunodeficiency virus/hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands. Clinical Infectious Diseases. 2018 May;66:1352-9.
- Boerekamps A, van den Berk GE, Lauw FN et al. Declining hepatitis C virus (HCV) incidence in Dutch human immunodeficiency virus-positive men who have sex with men after unrestricted access to HCV therapy. Clinical Infections Diseases. 2018 May;66:1360-5.
- Belperio PS, Chartier M, Gonzalez RI, et al. Hepatitis C care in the Department of Veterans Affairs: building a foundation for success. Infectious Disease Clinics of North America. 2018;32:281-92.
- Mera J, Vellozzi C, Hariri S. Identification and clinical management of persons with chronic hepatitis C virus infection – Cherokee Nation, 2012–2015. Morbidity and Mortality Weekly Report, Centers for Disease Control and Prevention. 2016 May;65(18).
About the author(s)
Rivka Kushner is CATIE’s Knowledge Specialist in Hepatitis C. She has a Master’s of Public Health in Health Promotion from the University of Toronto. Before joining CATIE, Rivka worked on provincial and national research and knowledge exchange projects in workplace health and environmental sustainability.