Hepatitis C virus (HCV) is a significant health concern at the population level, affecting tens of millions of individuals globally. It is predominantly spread through contact with infected blood (whether it be via blood transfusions, or the sharing of syringes or needles, amongst other possibilities).
The majority of those with acute HCV infection end up developing chronic infection, due to their inability to sufficiently clear the virus. While highly effective direct-acting antivirals (DAAs) against HCV have been developed, so long as affected patients are not tested for indicators of HCV infection, they are unaware of their status and miss out on truly life-saving treatment.
The lack of testing for HCV antibodies and stalling in progression along the ‘care cascade’ in many regions of the world comes down to the epidemiology of HCV infection itself. For one, HCV infection often presents itself in the form of mild symptoms (or none at all) in the majority of patients. As a result, groups of patients who are experiencing asymptomatic acute HCV infection are less likely to be tested (and are hence lost along the care cascade), as they do not experience the signs that trigger them to visit a health professional (where downstream testing and care would be provided). Additionally, at a basic level, this could come down to a lack of access to information itself; members of the population who are unaware of the risk factors associated with HCV (such that it is typically spread through contaminated blood) or the availability of testing, are less likely to present themselves for testing (or providing the opportunity for treatment to be recommended).
We must also consider specific demographics that are disproportionately impacted by the HCV epidemic. This includes people who inject drugs, indigenous communities, the homeless, and the incarcerated. For some of these populations, testing and the various other aspects of the care cascade are inaccessible. Living in a rural community (including some indigenous communities) often presents a barrier to accessing medical infrastructure because of distance (meaning no medical professionals are nearby, nor are treatments readily available, preventing progression along the care cascade). A lack of trust in Western medicine (and/or a lack of culturally-specific programs in the health-care system) may dissuade historically marginalized and mistreated groups from seeking out diagnosis and care (thereby hampering progression along the care cascade). For other groups, such as those living in incarceration, testing and treatment is often not an option; testing is seldom offered despite the sharing of needles and blood contact in prison causing HCV to persist amongst inmates.
Sometimes, initial testing and/or care may be possible, but cannot be maintained. Loss to follow-up presents a relevant issue in the HCV ‘care cascade’; in rural communities and those lacking in financial resources especially, patients are lost at various points in diagnostic testing (with antibodies and RNA levels often being tested during two distinct patient visits) and during care/treatment as they are unable to adhere to the respective processes given their distant proximity from medical facilities. Finally, sometimes, care is accessible, but patients are hesitant to seek it out. With people who inject drugs at particular risk of developing HCV, the stigma associated with such practices dissuades these individuals from seeking out the diagnosis and care that they would benefit from (due to fear of negative associations of presenting in a medical setting for HCV diagnosis or treatment).
To effectively tackle and address disease burden, a comprehensive approach is required. The use of EMR to provide medical professionals with alerts and reminders regarding HCV testing guidelines or eligibility for screening (for HCV-specific antibodies) would be a wise broad-spectrum first step. Meta-analyses have demonstrated that this strategy has resulted in increased screening for HCV infection (via testing for antibodies) in cohorts of asymptomatic adults. This could be implemented in conjunction with increased knowledge transmission; education campaigns would be critical in increasing awareness about HCV and its risk factors (such that it can be transmitted via needles), thereby encouraging groups particularly at risk of HCV infection to in fact get screened for HCV antibodies.
As well, more specific processes could be adopted that deal with the distinct needs, barriers, and challenges experienced by the groups most disproportionately impacted by HCV infection. For those living in rural communities or the homeless, increased access to testing is a necessary change. Research has demonstrated that access to free testing, the provision of transportation mechanisms, and the establishment of mobile testing programs have all contributed to increased HCV antibody testing. Another alternative is the use of dry blood spot samples (DBS), which may be distributed to rural areas; without the need for medical professionals, patients may simply spot their blood on a filter paper for subsequent analyzing of antibody levels.
Yet another possible change that can be made in laboratory processes is an emphasis upon catering to patient’s preferences. An aversion to needles or another particular mechanism of sample collection may be the tipping point between an individual getting tested for HCV antibodies or not. Whether it be the use of DBS as opposed to a needle, or a mouth swab (which is considerably less invasive) as opposed to collecting blood at all, choice in terms of testing options has been demonstrated to be important to patients (thereby increasing the likelihood that samples will be collected for use in downstream analyses of HCV antibodies). Finally, given the prevalence of HCV amongst those who inject drugs, it may be useful to screen for HCV infection (by testing for antibodies from serum) by making it readily available (in the form of rapid tests or even finger pricks) in areas where people inject drugs.
A critical aspect in the process of diagnosing chronic HCV in a patient is the determination of HCV RNA presence. This would be a key determinant of the presence of an active HCV infection. The maximization of the number of people who get tested for HCV RNA is of the utmost importance. Unfortunately, in many countries, diagnosis is a two-step process, with testing for HCV antibodies preceding testing for HCV RNA. This presents the opportunity for loss to follow-up to occur, with many not showing up for the RNA test. One comprehensive solution is reflex testing, which involves the automatic testing of HCV RNA in the event that an HCV antibody test is positive. The fact is, patients are unlikely to present themselves on numerous occasions for distinct sample collections (for HCV antibody, HCV RNA, and genotype tests respectively), but they are comparatively more likely to show up for a single sample collection event. Hence, both HCV antibody and RNA tests can be performed on a single patient sample; some patient serum can be used for antibody testing, while the rest can be stored in EDTA-containing tubes to be used in downstream RNA standing. This one-step process (which saves patients a visit) undoubtedly closes a significant gap for individuals who cannot afford to reach a health care facility on a consistent basis.
Apart from closing the gap using this aforementioned strategy, other solutions that come to mind include more accessible HCV testing (as was previously mentioned for the testing of HCV antibodies, access to transportation or even pop-ups would be useful for increasing this aspect of the diagnostic process for HCV infection, as would rapid point-of-care RNA testing), developing a registry of HCV-positive patients (such that in the event that both antibodies and RNA can’t be tested for in the same visit, there is a record that allows the patient to be reminded of the advantage of an RNA test when they next visit), and increased outreach to patients (research has demonstrated that strategies such as texts and phone calls to patients previously tested for HCV antibodies have resulted in increased HCV RNA tests, relative to the control groups that were not subject to outreach).
References:
8. Blackburn NA, Patel RC, Zibbell JE. 2016. Improving Screening Methods for Hepatitis C Among People Who Inject Drugs: Findings from the HepTLC Initiative, 2012–2014. Public Health Rep 131:91–97.9. New lab process reduces time from hepatitis C testing to treatment in B.C. http://www.bccdc.ca/about/news-stories/stories/2020/new-lab-process-reduces-time-from-hepatitis-c-testing-to-treatment-in-b-c. Retrieved 4 October 2023.
