Now Is the Time to Quickly Eliminate Barriers Along the Hepatitis C Cascade of Care

(See the Major Article by Lamoury et al, on pages 1889–96.) The progress made in the evaluation and treatment of hepatitis C virus (HCV) infection over the last 5 years is nothing short of astonishing. Irrespective of clinical settings or social demographic characteristics, direct-acting antiviral (DAA) therapy achieves cure rates well over 90% [1]. Furthermore, excellent salvage regimens are now available to provide highly effective, short-duration, safe treatments to those few patients for whom the first prescribed regimen is unsuccessful [2]. The need for liver biopsy has been largely eliminated by technological advances (ie, transient elastography) and the use of easily obtained laboratory measures providing well-validated noninvasive calculated estimates of liver fibrosis. In reality, fibrosis scores are more important for long-term hepatocellular carcinoma surveillance than they are for selecting DAA treatment candidates: everyone with confirmed HCV infection should be offered treatment [3]. At this point in the global response to HCV, confirmation of infection is the key problem faced by current efforts to eliminate HCV [4]. Many HCV-infected people have yet to receive a diagnosis, and for others, positive serological screening results are never followed up by confirmatory testing. This challenge to case identification is most acutely evident in populations less likely to engage and remain in health care [5]. These same groups, including street youths, homeless individuals, and incarcerated individuals, are also often more likely to actively participate in risk behaviors associated with HCV transmission. The development of point-of-care HCV RNA testing of capillary blood specimens obtained by finger stick represents another biomedical advance, along with transient elastography and interferon-free DAA treatment, that increases the feasibility of HCV infection cure in individuals and of HCV eradication globally. In this issue of The Journal of Infectious Diseases, Lamoury et al describe the Xpert HCV Viral Load finger stick assay [6]. Diagnostic confirmation of HCV is provided with high sensitivity and specificity, using an easily obtained drop of whole blood obtained by finger stick. The turnaround is only 1 hour, thereby addressing concerns about loss to follow-up. The combination of rapid HCV RNA testing, noninvasive assessment of fibrosis, and easy-to-take oral medications enables HCV detection and treatment in the most challenging of locations and circumstances. This assay does require further development before it is ready for everyday use. Among those with whole-blood samples obtained by finger stick (n = 223), a valid result could not be obtained for 18 (8%; for 7, there were errors due to low sample volume, and for 11, there were errors due to internal control being out of range). The sensitivity and specificity of the results would not be 100% if the samples that “failed to provide a result” [6] were included in the reported calculation. Eight percent represents a clinically relevant concern, as these individuals would experience an hour lost while waiting for a result that is invalid. It is plausible that the frequency of samples that “failed to provide a result” will be higher when the test is administered by lesser trained, nonresearch staff. Furthermore, according to the authors, the cartridge used in this study requires further development. These issues are raised as a reminder that, although close, this device is not quite ready for prime time, but it soon will be. When this and other rapid tests are ready, it is hoped that manufacturers remember that commercial pricing will have a critical impact on uptake and impact of this technology in the field. Although not assessed for this purpose, this assay could also be used for determining the outcome of HCV antiviral therapy, which would further streamline the cascade of care by eliminating the current practice that requires patients to present to a blood laboratory for sustained virological response testing, followed by a trip to the clinic to obtain the results. The prospect of patients self- collecting a capillary blood sample, loading the cartridge, and then either bringing the cartridge to the clinic or sending it there by mail or courier would increase efficiency, as well as save time and money. Use of this test may also prove of value in a select group of patients receiving DAA therapy, as a means of evaluating adherence. In most instances, there is no need to monitor HCV RNA levels during treatment, because adherent patients almost always achieve virologic suppression during treatment, and, for those who do not, detectable virus does not predict subsequent treatment failure and/or relapse [7]. However, in some instances medication adherence cannot be reliably determined. In these cases, the use of a rapid, reliable point-of-care test could be valuable in demonstrating virologic suppression and presumed DAA adherence. In this evaluation, the agreement between the Xpert and Abbott assays was excellent in 16 study participants receiving DAA treatment at the time of testing. Rapid viral detection technology is likely to be of great benefit in other disease areas. As an example, rapid detection of cytomegalovirus disease in the transplantation setting would inform the decisions to initiate antiviral therapy and interrupt dosing [8]. This could allow for more-rapid treatment initiation; reduced toxicity, by allowing for earlier interruption of empirical antiviral treatment in those with negative test results; better therapeutic outcomes; and cost savings. Among an extensive list of infectious diseases, the diagnosis of herpes simplex virus meningoencephalitis is another example for which a rapid nucleic acid detection test result could influence treatment, patient exposure to antimicrobials, and cost [9]. Population screening for case identification and for resource-allocation planning remains a major challenge to achieving HCV elimination. This technology eliminates one step along the cascade of care (ie, HCV RNA testing for confirmation of positive serologic test results) and provides a far easier means of identifying cases (ie, collection of a single capillary blood specimen, rather than 2 separate collections of venous blood specimens) [10]. These and other commercially available point-of-care tests could be made available to the public, further reducing barriers to screening (ie, the need to visit a healthcare facility). Contact information for regional healthcare facilities providing HCV education, work-up, and treatment could be provided at the point of access (by retailers selling these rapid tests, as well as by public health and medical clinics), further reducing barriers to HCV care engagement. Personal handheld device application links could be included in the packaging for HCV education purposes, as well as to provide information regarding regional HCV clinics where treatment could be accessed. These types of strategies place control of care directly in the hands of people living with HCV, in contrast to most current models of HCV care, in which access requires overcoming the barrier of obtaining a consult to a clinic. Easy, confidential access to rapid point-of-care HCV testing for individuals at risk of exposure to HCV (eg, people who inject drugs and men who have sex with men) would result in more-rapid linkage to care and a reduction in the risk of additional infections within that person’s network of contacts. Multiple advances in technologies and medications now allow for rapid diagnosis, work-up, and treatment of HCV infection. Where enabled, healthcare providers have scaled up the number of cases of treatment initiation multifold [11]. In many countries, there has been a similar rapid response by policy makers and funders to implement national screening strategies and provide universal reimbursement for DAA treatment, to ensure that patients benefit from these advances [12, 13]. Regrettably, these obvious actions required to address all steps along the cascade of care have not been embraced in all areas. Until screening and funding policies catch up to the rest of the field, those living with HCV will continue to experience unnecessary morbidity and mortality, no matter the speed by which the diagnostic tools yield a diagnosis. Potential conflicts of interest. C. L. C. is a consultant for Gilead, Abbvie, and Merck.

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