What interventions can be used to improve hepatitis C testing and linkage to treatment?

Canada is one of several countries that have committed to the World Health Organization (WHO) targets to eliminate hepatitis C as a public health threat by 2030.¹ Despite the availability of curative treatments for hepatitis C, worldwide uptake of testing and treatment remains low.² The World Health Organization estimates that 58 million people were living with hepatitis C worldwide in 2022,³ and in 2017, in Canada, it was estimated that nearly 200,000 people in Canada were living with chronic hepatitis C.⁴

The hepatitis C cascade of care is the path that people take to access hepatitis C treatment and be cured of hepatitis C. It includes steps related to hepatitis C testing, linkage to hepatitis C treatment, treatment initiation and confirmation of hepatitis C cure. With highly effective hepatitis C treatment using direct-acting antivirals (DAAs), simplifying approaches to testing and linkage to treatment through use of evidence-based solutions can help to achieve hepatitis C elimination goals.²

This article summarizes a systematic review and meta-analysis aiming to identify evidence-based interventions to improve hepatitis C care. This includes hepatitis C screening testing, which is referred to as antibody testing in this article, and hepatitis C confirmatory testing, which is referred to as RNA testing in this article, as well as linkage to care and treatment initiation with DAAs.²

What kind of research does the systematic review include?

The systematic review contains research on interventions to improve hepatitis C testing, linkage to care and treatment initiation.

One hundred and forty-eight studies were included in the review (47 randomized control trials and 101 non-randomized studies). A study was included if it:

• involved people at risk of hepatitis C or who had hepatitis C;
• implemented an intervention;
• included a comparison or control group; and
• focused on at least one of the following outcomes: hepatitis C antibody testing uptake, hepatitis C RNA testing uptake, linkage to hepatitis C care and treatment initiation with DAAs.

Eighty-seven studies focused on hepatitis C antibody testing, 23 on hepatitis C RNA testing, 37 on linkage to care and 41 on hepatitis C treatment initiation; some studies focused on more than one of these topics.

Study settings included primary care or general practice, hospital outpatient or tertiary clinics, drug treatment centres, population-based services, emergency departments, hospital inpatient units, prisons and others. Forty-four studies focused on birth cohorts, 44 on the general population, 13 on people in prison, 24 on people who use drugs (17 of which included people who inject drugs), 9 on people receiving opioid agonist therapy, 6 on people attending drug/alcohol services, 7 on a mix of populations, and 43 on other populations.

Which interventions improved hepatitis C testing, linkage to care and treatment initiation?

Hepatitis C antibody testing detects antibodies in the blood to determine if a person has ever had a hepatitis C infection. A positive test result means that a person has antibodies for hepatitis C and has had hepatitis C at some point in their life. The antibody test alone cannot tell whether a person currently has a hepatitis C infection, but it is typically the first step of hepatitis C testing and is an entry into the cascade of care.

Through combining data from multiple studies (pooling data), the authors found that the interventions that significantly improved uptake of hepatitis C antibody testing were:

• point-of-care (POC) antibody testing;
• dried blood spot testing (along with POC antibody testing, it has the ability to bring testing to more diverse, non-clinical locations without the requirement for venipuncture);
• opt-out screening where everyone is tested for hepatitis C unless they choose not to be;
• medical chart reminders for providers that alert them to test for hepatitis C if the patient is eligible or where it is recommended;
• provider education (e.g., information on hepatitis C testing guidelines);
• provider care coordination (i.e., having an individual manage interactions between healthcare providers);
• patient reminders for testing or treatment;
• patient education; and
• improving clients’ recall of recently learned information (i.e., memory practice).

In single studies, several interventions were found to significantly improve the uptake of hepatitis C antibody testing, including on-site oral swabs for hepatitis C antibody testing, financial incentives to providers, direct solicitation of patients (e.g., a study recruiter approaching someone in a clinic waiting room and offering testing), implementation of a policy related to systematic or broader testing rather than testing on request or sporadically, use of a risk-based screening tool, nurse-led care, pharmacist-led treatment, POC hepatitis C antibody testing, memory practice, dried blood spot testing and directly observed therapy (e.g., hepatitis C medications provided in a healthcare setting along with other regularly accessed medications or services such as opioid agonist therapy).

Hepatitis C RNA testing determines if someone currently has a hepatitis C infection by detecting the presence of the virus in the blood (through testing for the genetic material of the hepatitis C virus).

Through combining data from multiple studies (pooling data), the authors found that the interventions that significantly improved the uptake of hepatitis C RNA testing were:

• medical chart reminders for providers that alert them to test for hepatitis C if the patient is eligible or where it is recommended; and
• reflex RNA testing (completing hepatitis C antibody and hepatitis C RNA tests from blood drawn during a single interaction).

Single studies showed that interventions focused on provider education and provider care coordination significantly increased the uptake of hepatitis C RNA testing.

Linkage to hepatitis C care is the first visit with a hepatitis C medical service provider that takes place after diagnosis.

Through combining data from multiple studies (pooling data), the authors found that interventions that significantly improved linkage to care were:

• medical chart reminders for providers that alert them to test for hepatitis C if the patient is eligible or where it is recommended;
• POC antibody testing, which allow for on-site and immediate testing;
• provider education (e.g., information on hepatitis C testing guidelines);
• integrated care (i.e., co-locating hepatitis C services within the same physical space as other medical services); and
• patient navigation or care coordination (i.e., support or assistance to help clients manage healthcare interactions).

Single studies showed that dried blood spot testing, reflex RNA testing and on-site oral swab collection for hepatitis C antibody testing significantly improved linkage to care.

Treatment initiation describes when a person starts treatment for hepatitis C.

By combining data from multiple studies (pooled data), the authors found that interventions that significantly improved rates of hepatitis C treatment initiation using DAAs were:

• integrated care (i.e., co-locating hepatitis C services within the same physical space as other medical services); and
• patient navigation (or care coordination).

These approaches can bring services to spaces where people are already receiving care and aid with managing interactions with the health care system.

Single studies showed that medical chart reminders, POC antibody testing, broadened testing and treatment criteria (e.g., removal of restrictions on hepatitis C treatment), motivational interviewing (i.e., a counselling approach that helps clients to understand and resolve ambivalence) and nurse-led care all significantly increased treatment initiation.

Which interventions demonstrated improvements across the hepatitis C cascade of care?

Three interventions examined in the review were shown to be effective across three or more stages of the hepatitis C cascade of care.

• POC antibody testing has been demonstrated to improve hepatitis C antibody testing uptake (pooled data), linkage to care (pooled data) and the uptake of DAA treatment (single study). It does this by facilitating on-site, low-threshold hepatitis C testing and simplifying the testing pathway by decreasing the number of visits required to get a diagnosis. POC antibody testing using a finger-prick blood sample can also eliminate the need for venipuncture, which can be a barrier to testing for people who inject drugs, who may have poor venous access.
• Medical chart reminders are alerts for providers that remind them to test for hepatitis C if the patient is eligible or where it is recommended. They are relatively simple to implement and remove barriers for providers (e.g., outdated knowledge of testing guidelines, competing healthcare needs). This intervention has been demonstrated to improve uptake of hepatitis C antibody testing (pooled data), hepatitis C RNA testing (pooled data), linkage to care (pooled data) and treatment uptake (single study).
• Provider education (e.g., educational sessions, seminars on stages of the cascade of care) can support strengthening competency in and improving motivation to engage with hepatitis C care for service providers. This intervention was shown to improve rates of hepatitis C antibody testing (pooled data), hepatitis C RNA testing (single study) and linkage to care (pooled data).

What are the implications of the review for service providers?

The systematic review and meta-analysis identified several interventions that have been demonstrated to improve uptake across the hepatitis C cascade of care. Many of these interventions have already been implemented or explored in the Canadian context (e.g., POC antibody testing, dried blood spot testing, integrated care). With highly effective and widely accessible hepatitis C DAA treatment in Canada, a focus on eliminating barriers to hepatitis C testing (e.g., POC antibody testing, dried blood spot testing, reflex testing), linkage to care (e.g., patient navigation, care coordination, integrated care) and treatment initiation is crucial to supporting people to be cured of hepatitis C and to reaching hepatitis C elimination goals.

Results from this study provide service providers and programs with a menu of options rooted in evidence and aimed at addressing common challenges in hepatitis C testing, linkage to care and treatment initiation. Choices about which interventions to implement and how to implement them will depend on the unique challenges and needs associated with particular populations and settings and how readily the interventions can be tailored effectively to address those needs.

When considering this review, it is important to remember the following:

Many of the studies that considered testing and linkage to care outcomes were conducted when interferon-based treatment was still offered to patients. Interferon-based hepatitis C treatment was a less effective and less tolerable treatment approach and is no longer used to treat hepatitis C. The results from these studies could have affected linkage to care and treatment initiation, although strategies that worked with interferon-based treatments probably still have utility with DAAs.

Additionally, many interventions included in this analysis did not have the statistical power necessary to assess the outcomes of complex interventions (e.g., interventions with peer support) and did not adjust for potential confounding variables, all of which reduce the quality of the data.

What is a systematic review and meta-analysis?

Systematic reviews are important tools to inform evidence-based programming. A systematic review is a critical summary of the available evidence on a specific topic. It uses a well-defined search strategy to identify all the studies related to a specific research question. Relevant studies can then be assessed for quality and summarized to identify key findings and limitations.

A meta-analysis is a method to pool numerical data from multiple studies. If the studies included in a systematic review contain numerical data, authors can use statistical methods to calculate summary (“pooled”) estimates. These pooled estimates can provide a better overall picture of the topic being studied.

Related resources

Single-visit hepatitis C testing and linkage to care through a mobile unit

Shelter-based hepatitis C treatment at the Calgary Drop-in Centre

CATIE statement on hepatitis C treatment efficacy among people who use drugs

Hepatitis C: An In-Depth Guide

References

1. Canadian Network on Hepatitis C. Blueprint to inform hepatitis C elimination efforts in Canada. Montreal: Canadian Network on Hepatitis C; 2019. Available from: https://www.canhepc.ca/sites/default/files/media/documents/blueprint_hcv_2019_05.pdf
2. Cunningham EB, Wheeler A, Hajarizade B et al. Interventions to enhance testing, linkage to care, and treatment initiation for hepatitis C virus infection: a systematic review and meta-analysis. Lancet Gastroenterol Hepatology. 2022;7(2):P426-45.
3. World Health Organization. Hepatitis C. Geneva: World Health Organization; 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c#:~:text=Globally%2C%20an%20estimated%2058%20million,carcinoma%20(primary%20liver%20cancer).
4. Public Health Agency of Canada. People living with hepatitis C (HCV): Canada, 2017. Infographic. Ottawa, ON: Public Health Agency of Canada [Online]; 2020. Available from: https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/diseases-conditions/infographic-people-living-with-hepatitis-c-2017/HCV-Infographic-EN-v11.pdf

About the author(s)

Shannon Elliot is 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.

Amanda Giacomazzo is CATIE’s manager of community programming. She has a master’s degree in health science with specialised training in health services and policy research and previously worked in knowledge translation and public health at the provincial level.