Hepatitis C reinfection: Risks, realities and responses

Prevention in Focus PiF 2023 Fall

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Reinfections are a reality of hepatitis C work. Direct-acting antivirals cure hepatitis C, but being cured does not result in immunity to hepatitis C: a person can get hepatitis C again if they are exposed to the virus. For most people, the risk of reinfection is low, but because of the possibility of reinfection after cure, some healthcare providers have been hesitant to provide hepatitis C treatment to individuals with ongoing risks for infection. De-stigmatizing reinfection and understanding what reinfection rates can tell us about who hepatitis C programs are reaching is essential for advancing hepatitis C care.  

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This article will establish an understanding of what reinfections are, examine the realities of reinfection rates across affected populations and explore effective strategies to address reinfections across the cascade of hepatitis C care.

What are hepatitis C reinfections?

A person can get hepatitis C again if they are exposed to the virus after they are cured with treatment or have cleared the virus on their own. This is called reinfection. Reinfections follow the same principles as a primary (first) hepatitis C infection — they are transmitted through blood-to-blood contact (e.g., sharing equipment for injecting drugs) and are cured through treatment with direct-acting antivirals (DAAs). The cure rate for treatment of hepatitis C reinfections is as high as it is for treatment of a primary (first) hepatitis C infection.1  

Populations most impacted by reinfection

For most people, the risk of hepatitis C reinfection is low. The majority of people who are cured through treatment do not experience hepatitis C reinfection.2 However, reinfection can happen among people who have ongoing risks for hepatitis C after they have been treated and cured.2,3,4

Research indicates that hepatitis C reinfection is more common among people who inject drugs, as well as gay, bisexual and other men who have sex with men (gbMSM) who use injection drugs and/or who have HIV.4,5,6 These groups face a greater likelihood of reinfection because they have a combination of ongoing risk factors for hepatitis C infection and are disproportionally impacted by structural and social factors (such as criminalization of and stigma from drug use) that can hinder their access to healthcare and prevention services, such as needle and syringe programs and condoms.

Hepatitis C reinfection among people who inject drugs

Research shows that among people who inject drugs, the rate of hepatitis C reinfection is highest among people with recent injection drug use (within six months before starting treatment, during treatment, at the end of treatment or during post-treatment follow-up) and lowest among people who are receiving opioid agonist treatment (OAT) independent of drug use.6 This is shown in a meta-analysis of 36 studies (nine of which were conducted in Canadian contexts) that estimated the rate of hepatitis C reinfection after treatment among different groups of people who use drugs.

The meta-analysis found:

  • 5.9 hepatitis C reinfections per 100 person-yearsa  among people with recent drug use (injecting or non-injecting)
  • 6.2 hepatitis C reinfections per 100 person-years among people who had recently injected drugs 
  • 3.8 hepatitis C reinfections per 100 person-years among people receiving OAT, independent of drug use6

Further, the meta-analysis found that although reinfection after successful treatment of hepatitis C sometimes occurs, the rate of reinfection among people with recent injection drug use is lower than the rate of primary (first) hepatitis C infections in this population (6.2 infections per 100-person years vs. 23 infections per 100-person years).6

People who inject drugs in prison contexts

People who inject drugs in prison settings have a higher rate of hepatitis C reinfection than people who inject drugs in the general population.6,7,8 This can be linked to having limited or no access in prison environments to harm reduction services to prevent hepatitis C transmission, namely access to harm reduction supplies that would reduce sharing of equipment.7,9

Hepatitis C reinfection among gay, bisexual and other men who have sex with men

Research shows that among gbMSM, injection drug use and living with HIV are both associated with an increased risk of hepatitis C reinfection.5,10 A Canadian cohort study using data from approximately 1.7 million individuals tested for hepatitis C and HIV in British Columbia estimated a reinfection rate of 1.88 reinfections per 100 person-years for gbMSM.10 Among gbMSM living with HIV, the reinfection rate was 3.13 reinfections per 100 person-years. Among gbMSM who used injection drugs, the reinfection rate was 3.25 reinfections per 100 person-years.10

How do reinfections impact hepatitis C care?

The benefits of treating hepatitis C reinfections

All people are deserving of the health and well-being benefits of hepatitis C treatment for a primary infection or a reinfection. These include reduced risks of long-term health impacts such as cirrhosis (advanced liver injury), liver cancer, liver failure and liver-related death. Further, engaging in hepatitis C care can provide additional benefits to individuals such as access to other care and supports including harm reduction services or connection to other services including housing.

Access to treatment for reinfection is also important for population health.11 A treatment as prevention approach, which can be considered a cure as prevention approach with hepatitis C, diagnoses and treats both primary infections and reinfections early to help prevent onward transmission of hepatitis C, reduce the population prevalence of hepatitis C and reduce morbidity and mortality related to liver disease.11

Hesitancy to treat people at ongoing risk for reinfection

Hepatitis C reinfections after treatment and cure have been perceived by some as a treatment failure. These perceptions can have damaging effects as they have sometimes resulted in treatment being withheld from individuals with ongoing risks12 despite universal treatment recommendations.13,14 This is largely due to the high cost of hepatitis C treatment and concern about the potential repeated cost of treatment for reinfection, and in some cases it may be due to restrictive or unclear treatment coverage policies for hepatitis C reinfection.

Normalizing reinfections as a reality of the hepatitis C response

Recently, there has been a push to consider how reinfections can be accepted as a reality of hepatitis C work — emphasizing the benefits of treatment for all and repositioning reinfections as a useful performance indicator. If treatment is universally offered for reinfections and reinfections are seen as an opportunity to strengthen programs, they could be used to better understand the effectiveness of interventions across the care cascade:

  • Reinfections can confirm whether community health programs are reaching individuals at risk for reinfection. If no cases of reinfection are seen, it is possible that those clients at the highest risk of hepatitis C reinfection are not being reached for testing and treatment. Alternatively, low numbers of people with reinfection can also be used as a measure of effective population-level access to treatment and prevention.
  • Reinfection can be used to identify groups with a higher burden of hepatitis C and tailor interventions accordingly.15
  • Reinfections may also indicate where there may be barriers to accessing prevention strategies. Persistent reinfections may indicate that prevention strategies could be strengthened and expanded.16

Programming and policy implications

Strategies for service providers

A multi-pronged approach is considered the most effective approach to reducing reinfections. Effective responses to address reinfections should be built upon best practices in hepatitis C prevention, testing and treatment, as well as the provision of other essential supports for people with ongoing risks for exposure.16

Preventing reinfections

Prevention approaches that are used to prevent a primary hepatitis C infection also prevent reinfections. They include access to essential harm reduction resources and services, such as needle and syringe programs, opioid agonist treatment and safe consumption sites, and access to sexual health services and supplies, such as condoms. When an individual is diagnosed with a hepatitis C infection, engaging with, testing and treating their injecting and sexual partners and networks at the same time will also help to prevent reinfection.17

  • It is important to communicate the risk of hepatitis C reinfection to people who are at ongoing risk for hepatitis C. Service providers can counsel clients on how to use prevention strategies consistently and correctly,17 regardless of their hepatitis C status.
  • Service providers can facilitate access to harm reduction and sexual health services to reduce the likelihood of hepatitis C reinfections, including access to resources for safer drug use and safer sex.

Testing for reinfections

Routine testing for hepatitis C for those at risk of reinfection has been recommended in national and international guidelines as a strategy to diagnose reinfections in their early stages and to allow people to be connected to hepatitis C treatment and care.11,18,19

  • Service providers, while maintaining a judgment-free environment, can encourage clients who have been cured of hepatitis C and have ongoing risks for reinfection to be tested every six to 12 months for hepatitis C. People who have had hepatitis C before will have hepatitis C antibodies for life and should be tested for reinfection with a test that detects a current infection, such as an RNA test.18,19

Treatment for reinfections

Canadian20 and global11,21 treatment guidelines recommend offering treatment to all people with a chronic hepatitis C infection, which includes people at risk for reinfection and with a reinfection. As such, everyone should be offered treatment for their primary (first) hepatitis C infection and those with a hepatitis C reinfection should be offered treatment, without discrimination or shame. Treatment of reinfection may reduce the potential for onward transmission among people with ongoing risk behaviours. 

  • Treating a person with a reinfection is the same clinically as treating a person with hepatitis C for the first time. Clinical guidelines for the treatment of hepatitis C in Canada recommend that all people with a chronic hepatitis C infection should be offered treatment, regardless of ongoing risks for hepatitis C reinfection, such as drug use.20 However, public drug programs and private drug insurance plans may have different policies for covering treatment for reinfection.22 Service providers can work with their clients to navigate treatment coverage options.
  • Prioritizing ongoing testing after people have been cured and providing treatment for reinfection will also play a role in reducing the overall prevalence of hepatitis C in the community. This strategy may include testing and treatment of injecting and sexual partners and networks.17
  • There is currently inconsistent access to treatment for reinfection in Canada.22 Removing barriers to treatment access for reinfection benefits both individual and population health. Service providers may choose to advocate for increased access to treatment for all reinfections.

Related resources

a Person-years is a measurement that describes the length of time over which a group of people were followed. In a given study, it combines the number of participants and the number of years they participated in the study. For example, a study following 100 people for one year each would provide 100 person-years of data.16

References

  1. Carson JM, Hajarizadeh B, Hanson J et al. Effectiveness of treatment for hepatitis C virus reinfection following direct acting antiviral therapy in the REACH-C cohort. International Journal of Drug Policy. 2021;96:103422.
  2. Wyles DL, Kang M, Matining RM et al. Continued low rates of hepatitis C virus (HCV) recurrence in HCV/HIV- and HCV-infected participants who achieved sustained virologic response after direct-acting antiviral treatment: final results from the AIDS Clinical Trials Group A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS). Open Forum Infectious Diseases. 2021;8(12): ofab511.
  3. Marshall AD, Marinello M, Treloar C et al. Perceptions of hepatitis C treatment and reinfection risk among HIV-positive men who have sex with men and engage in high risk behaviours for hepatitis C transmission: the CEASE qualitative study. International Journal of Drug Policy. 2022;109:103828.
  4. Rossi C, Butt ZA, Wong S et al. Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort. Journal of Hepatology. 2018;69:1007-14.
  5. Falade-Nwulia O, Sulkowski MS, Merkow A et al. Understanding and addressing hepatitis C reinfection in the oral direct acting antiviral era. Journal of Viral Hepatitis. 2018;25(3):220-27.
  6. Hajrizadeh B, Cunningham EB, Valerio H et al. Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: a meta-analysis. Journal of Hepatology. 2020;72:643-57.
  7. Hajarizadeh B, Grebely J, Byrne M et al. Evaluation of hepatitis C treatment-as-prevention within Australian prisons (SToP-C): a prospective cohort study. Lancet Gastroenterology and Hepatology. 2021;6:533-46.
  8. Yeung A, Palmateer NE, Dillon JF et al. Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs. Journal of Hepatology. 2022;76:549-57.
  9. Lafferty L, Rance J, Grebely J et al. Perceptions and concerns of hepatitis C reinfection following prison-wide treatment scale-up: counterpublic health amid hepatitis C treatment as prevention efforts in the prison setting. International Journal of Drug Policy. 2020;77:102693.
  10. Adu PA, Rossi C, Binka M et al. HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men. Liver International. 2020;41:482-93.
  11. World Health Organization. New recommendation on hepatitis C virus testing and treatment for people at ongoing risk of reinfection: policy brief. Geneva: World Health Organization; 2023. Available from: https://www.who.int/publications/i/item/9789240071872
  12. Asher AK, Portillo CJ, Cooper BA et al. Clinicians’ views of hepatitis C virus treatment candidacy with direct-acting antiviral regimens for people who inject drugs. Substance Use & Misuse. 2016;51(9):1218-23.
  13. Graf C, Mucke MM, Dultz G et al. Efficacy of direct-acting antivirals for chronic hepatitis C virus infection in people who inject drugs or receive opioid substitution therapy: a systematic review and meta-analysis. Clinical Infectious Diseases. 2019;70:2355-65.
  14. Aspinall EJ, Corson S, Doyle JS et al. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clinical Infectious Diseases.  2013;57(Suppl 2):S80-89.
  15. Hagan H, Jordan AE, Neurer J et al. Incidence of sexually transmitted hepatitis C virus infection in HIV-positive men who have sex with men. AIDS. 2015;29:2335-45.
  16. Hepatitis C Trust: Reframing reinfection: towards sustained hepatitis C elimination in the UK. London (UK): The Hepatitis C Trust and HCV Action; 2022 Available from: https://www.hepctrust.org.uk/wp-content/uploads/2022/11/Reframing-Reinfection.pdf
  17. Martinello M, Dore GJ, Matthews GV. Strategies to reduce hepatitis C virus reinfection in people who inject drugs. Infectious Disease Clinics of North America. 2018;32:371-93.
  18. CATIE. CATIE statement on hepatitis C treatment efficacy among people who use drugs. Toronto (ON): CATIE; 2021. Available from: https://www.catie.ca/catie-statement-on-hepatitis-c-treatment-efficacy-among-people-who-use-drugs
  19. The Canadian Network on Hepatitis C. Blueprint to inform hepatitis C elimination efforts in Canada. Montreal (QC): The Canadian Network on Hepatitis C Blueprint Writing Committee and Working Groups; 2019. Available from: https://www.canhepc.ca/sites/default/files/media/documents/blueprint_hcv_2019_05.pdf
  20. Shah H, Bilodeau M, Burak KW et al. The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver. Canadian Medical Association Journal. 2018;190(22):E677-87.
  21. World Health Organization. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. Geneva: World Health Organization; 2018. Available from: https://www.who.int/publications-detail-redirect/9789241550345
  22. Snell G, Marshall A, van Gennip J et al. Public reimbursement policies in Canada for direct-acting antiviral treatment of Hepatitis C virus infection: a descriptive study. Canadian Liver Journal. 2023;6(2): 190-200.

 

About the author(s)

Shannon Elliot was CATIE’s knowledge specialist in hepatitis C. She has a master of public health degree and has held knowledge mobilization, policy and research positions in the areas of medical education, sexual assault and intimate partner violence.