Now that we know which populations are most affected by HCV, we can begin to think about approaches to implementing HCV screening. There were notable changes to several healthcare guidelines recently, which should make it easier for HCPs to routinely offer testing and for patients to routinely accept testing.

The AASLD/IDSA guidelines, which are also supported by the US Preventive Services Task Force, recommend universal, opt-out, one-time HCV testing for all individuals aged 18 or older. Individuals who are younger than 18 years of age should also be offered HCV testing if they have a history of exposures that increase HCV infection risk, or if their current circumstances are associated with an increased risk of HCV exposure.

In addition, HCV testing is now recommended for each pregnancy as part of routine prenatal care.⁸

Annual testing is recommended for individuals at increased risk of HCV infection. These include all people who inject drugs, men living with HIV who have unprotected sex with other men, or men who have sex with men, who are being prescribed PrEP for HIV infection.⁸ 

Let us delve a little deeper into what activities confer increased risk for HCV. The highest-risk activities include current or past injection drug use. HCV is so easily transmitted that even 1 episode of injection drug use with shared paraphernalia is a high enough risk for HCV acquisition, so those individuals should be tested.⁸

In addition to injection drug use, other risk activities include using intranasal illicit drugs. Men who have sex with other men, especially if they are engaging in chemsex (a practice in which individuals use drugs while having sex) are also at increased risk for HCV exposure.⁸

Risk exposures that put people at higher risk for HCV acquisition include being on hemodialysis and percutaneous or parenteral exposures in unregulated settings. Of note, getting tattoos can be a high-risk exposure for HCV acquisition if they are done in places that are not licensed, or if those tattoos are received in jail or prison.⁸

Individuals who may be at higher risk of occupational HCV exposure include public safety, emergency medical, and HCPs who may experience sharp or needlestick injuries or mucosal exposures to HCV-infected blood.

Healthcare exposures also are important sources of transmission, including receipt of an organ transplant or transfusion from a donor who was later found to have HCV, receipt of a transfusion or organ prior to 1992, or receipt of clotting factor concentrates manufactured prior to 1987. Children born to women living with HCV are considered to be at risk for mother-to-child transmission.⁸

Because HCV in jails and prisons is prevalent, people who were ever incarcerated are also at increased risk for HCV infection just by virtue of their previous incarceration, with studies reporting that recent incarceration was associated with up to a 62%  increase in HCV acquisition risks.^8,9

Finally, other conditions and circumstances that are associated with an increased risk of HCV infection include: living with HIV or hepatitis B virus (HBV) infection, being sexually active and about to initiate PrEP, having chronic elevations in liver enzymes or other signs of chronic hepatitis or chronic liver disease, and being either the recipient or donor of a solid organ transplant.⁸

The approach to HCV testing has traditionally been a 2-step algorithm, starting with an HCV antibody test. The presence of HCV antibodies is a marker of exposure, and does not necessarily indicate active, ongoing infection.

If the antibody test is nonreactive, meaning that no antibody is detected, the testing algorithm will often stop there. The exception is if there is a concern that the individual has an acute HCV infection and it is too early for the antibody response to be detected.⁸ This can occur if a person has had a recent exposure, as it can take 8-12 weeks for antibodies to develop. In this case, this person may have an active HCV infection but may not have developed detectable levels of antibody, resulting in a nonreactive test despite active infection. As such, in cases of recent exposures or concern for acute infection, the recommendation is to also get a confirmatory HCV RNA test.⁸

If the antibody test is reactive it indicates a prior exposure to HCV. However, it is important to determine if a person has ongoing infection. The way to do this is by testing for HCV RNA.⁸

If HCV RNA is not detected, then we can conclude that this person does not have current HCV infection. A positive antibody test and a negative RNA test suggests that this individual was previously exposed to HCV and either cleared the infection spontaneously or was cured with previous treatment.⁸

However, depending on the indication for HCV testing in the first place, additional testing may still be required even if the HCV RNA test is negative. For example, if this individual were being tested for HCV owing to elevations in liver enzymes, additional workup is required to determine the etiology of transaminitis.⁸

Alternatively, a reactive antibody test and a positive RNA test would indicate a current HCV infection. These patients should be linked to care to access treatment and cure of their HCV.⁸

As you can see, the traditional algorithm for HCV testing is quite long. Patients likely see an HCP who orders the test,, then a phlebotomist who draws blood for the test. The blood is sent to a laboratory for testing, followed by a 1-2 week wait for the antibody test result.^10,11

A reactive antibody test demonstrates exposure only, not necessarily current infection, so the HCP must request another visit to the phlebotomist for another sample that is sent to another lab for HCV RNA testing. This process can take another 1-2 weeks.^10,11

There are multiple steps in this long journey to HCV diagnosis where a patient may be lost to follow-up. Because of this, many patients start but do not complete the testing algorithm. This necessitates alternate approaches to increase the likelihood that individuals will complete the appropriate testing and receive their results so they are aware of their HCV infection status.^10,11

One of these alternate approaches could be using rapid antibody tests. Data supporting the effectiveness of rapid antibody tests include a study from France that sought to determine whether point-of-care (POC) HCV antibody testing could lead to improved awareness of HCV infection status and linkage to care.

Adults seeking care at a free clinic in France were randomized to 1 of 2 study arms: One group had access to POC rapid HIV/HBV/HCV testing, with results available in 20 minutes; the second arm received standard-of-care serology-based testing in which a sample was drawn and sent to the laboratory for testing.¹²

The primary outcomes in this study were awareness of status and linkage to care. Overall, 98% of individuals who received POC rapid testing became aware of their hepatitis or HIV infection status, compared with only 64% in the standard, serology-based testing arm, a statistically significant difference.¹²

Twenty individuals in the POC, rapid testing arm had HCV infection compared with 18 individuals in the standard-of-care testing arm. Among those people, there was no difference in the number who were linked to care (90% in the rapid testing arm vs 83% in the standard-of-care arm; P = .7).¹²

However, investigators determined that the proportion of patients linked to care could be influenced by the potential number of infected people who were not tested. So a sensitivity analysis was performed to account for the missing data that included people who did not get tested (n = 47 participants in the standard-of-care arm and n = 3 in the POC arm), and they assumed a prevalence of disease equal to that of the general population. This sensitivity analysis found that the rate of linkage to care would have been 90% in the rapid testing arm and only 60% in the standard testing arm. If the assumptions made in the sensitivity analysis are correct, this is a statistically significant increase in linkage to care with POC testing.¹² 

Another alternative approach to shortening the long journey to HCV diagnosis is to use reflex HCV testing.

With this in mind, a study in the United Kingdom evaluated a single-step HCV testing algorithm, where both HCV antibody and RNA testing could be done on a single sample. First, the HCV antibody testing was performed, with reflex RNA testing to follow in the event of a reactive antibody test.¹³

This study assessed the rate of confirmatory HCV RNA testing preintervention (prior to implementation of the reflex HCV testing algorithm) compared with postintervention. In the preintervention period, only 70% of individuals received the required confirmatory testing. However, in the postintervention phase, 99% of individuals received the required confirmatory HCV RNA testing.¹³

These results suggest that the single-step algorithm with reflex HCV testing was associated with a notable increase in confirmatory RNA testing and could help prevent drop off from the HCV care cascade at that stage of awareness of HCV infection status.¹³

The POC HCV RNA test was recently approved in the United States. This test essentially allows for determination of detectable levels of HCV RNA during 1 encounter with a sample collected via finger prick and results available within 1 hour of testing. This allows for diagnosis and treatment initiation in just 1 visit.

POC HCV RNA testing has been successfully implemented in a wide range of settings, both in and outside the United States.^14,15

Data suggest that, compared with standard-of-care serology-based testing, POC assays are associated with reduced time to treatment initiation, increased treatment uptake, and reduced loss to follow-up.

Implementation of POC RNA testing in community-based settings has significant potential for reaching marginalized communities and ensuring awareness of hepatitis C viremia status in just 1 encounter.¹⁶

Altogether, this is a very exciting new tool with great potential to enhance our ability to move patients quickly along the HCV care continuum from testing, to awareness, to treatment and care. 

POC RNA testing may be particularly impactful in improving HCV diagnosis and linkage to care among incarcerated individuals.

In this prospective, controlled study in an Australian prison, 540 male participants were randomized to standard of care vs a “one-stop-shop” intervention that included POC RNA testing, HBV surface antigen testing, transient elastography to assess the stage of liver disease if needed, a nurse-led clinical assessment, and fast-tracked DAA prescription.¹⁷

Investigators reported that 26% of patients in the standard-of-care arm received HCV antibody and/or HCV RNA testing, compared with 99% of patients receiving POC HCV testing in the “one-stop-shop” intervention.

Among those tested in the standard-of-care arm, 18 individuals (29%) were diagnosed with current HCV infection. In the “one-stop-shop” arm, 30 individuals (10%) were diagnosed with current HCV infection. Almost twice as many HCV infections were diagnosed in the “one-stop-shop” arm compared with the standard-of-care arm.¹⁷

Of note, in the “one-stop-shop” group, the median time to HCV treatment initiation was shorter, DAA treatment initiation was more common, and cure rate was higher.¹⁷

In all, these early data show the feasibility of integrating POC RNA testing into HCV care in a prison setting. 

Despite the excitement around POC RNA testing, I believe there are still some aspects that could benefit from further optimization to increase the likelihood that people will receive their HCV test results and become aware of their status.

First, a faster time to result, ideally less than 10 minutes, would be critical in low-threshold settings such as harm reduction centers or mobile programs.

Second, lower cost would facilitate widespread uptake of POC testing. Currently the POC RNA platform, including the machine and the cartridges in which samples are placed, are very expensive, which is something few community-based organizations can afford. This cost might be a barrier to implementation in some settings.

Finally, it will be important that these platforms retain accuracy and ease of use, so that samples can be collected through a finger prick with no requirement for phlebotomy. 

A recent review evaluated evidence-based ways to enhance the HCV care cascade and identified 3 primary themes among these strategies: Simplify testing, engage patients in care, and support HCPs.¹⁸

Simplifying testing encompasses implementation of POC antibody testing, dried blood spot testing, reflex RNA testing, or opt-out screening.¹⁸

In addition, POC RNA testing should be considered in appropriate settings. Because of the cost associated with POC RNA testing, this method may be the most cost-effective in settings with a high prevalence of HCV, such as syringe service programs.¹⁸

The next theme includes strategies to engage patients in care. Some evidence-based strategies to do this include implementing patient reminders to complete testing, providing support to patients navigating the health system, and supporting linkage to care and treatment initiation through a wide range of trained staff, including patient or peer navigators with lived experience. Other models for engaging patients in care include involving HCPs such as social workers and nurses, in-patient navigation, and care coordination.¹⁸

Patient education is also critical to engagement in care. For many, there is a misconception that HCV is an innocuous disease with no potential for harm, or that there are no treatments for it, or that the only treatments available are the historical interferon-based treatments, which were associated with significant adverse effects. Patient education should focus on the potential risk of progression from liver disease to liver cirrhosis and cancer, and the availability of simple, safe, and effective treatments. Most of all, meeting patients where they are and ensuring there are places where they can easily access these treatments has great potential to improve HCV care engagement.¹⁸

Finally, we must provide support for HCPs who care for people with HCV. Hepatitis C virus is traditionally treated in specialty settings, but the advent of oral DAAs—specifically, the ease of use and the safety of these medications—has made it more possible than ever for HCV testing and treatment to be a part of routine care. Thus, it is increasingly important that HCPs in a range of settings are supported to provide HCV testing and treatment. This includes supporting HCPs in knowledge of HCV testing and treatment, using electronic medical record systems to help identify people who have not previously been tested, and providing alerts to HCPs so that they are reminded to offer this testing.¹⁸

So how do we achieve equitable HCV care?

The first goal is to increase awareness of HCV, and to make HCV prevention and testing more accessible. Ultimately, we want to make testing for HCV available in a range of settings to increase the likelihood that everyone is aware of their HCV status.^19,20

Meeting people where they are is key for expanding access to testing and treatment. This means that we have to expand access to HCV testing and treatment beyond specialist clinics and beyond hospitals to a wide range of community-based sites. This includes primary care mobile programs, syringe service programs, and sexual health clinics.^19,20

Then, in all settings where HCV care is provided, we must reduce stigma by ensuring that HCPs are comfortable with offering routine testing and treatment. This is supported by recent changes to the AASLD/IDSA HCV guidelines, and the US Preventive and Services Task Force, which now recommend one-time HCV testing in all adults, regardless of risk or exposure history.^19,20

So, what does it truly mean to meet people where they are? Consider places where people who are disproportionately affected by HCV are already accessing services. This includes substance use disorder treatment facilities, opioid treatment programs, harm reduction centers, syringe service and outreach programs, Federally Qualified Health Centers, sexual health clinics, mental health facilities, emergency departments, or even pharmacies.^7,21,22  

However, it is not enough to institute these services and expect people to come. To better reach individuals with HCV, we are going to have to conduct outreach and engage communities. HCV testing can be implemented in homes as well as community-based locations such as state fairs and health fairs. Performing HCV testing in mobile health clinics and shelters for unhoused individuals has potential to both identify people living with HCV and support linkage to care and initiation of HCV treatment. Lastly, implementing HCV testing and treatment in prisons can effectively meet the needs of people who are in carceral settings, who also have high prevalence of HCV.^7,21,22