OraQuick hepatitis C virus self-test: A new frontier in hepatitis C screening

Abstract

According to the World Health Organization, an estimated 58 million people worldwide are chronically infected with hepatitis C virus (HCV), yet only about 20% have been formally diagnosed. Traditional laboratory–based antibody and RNA assays require infrastructure and trained personnel, limiting their uptake in resource-limited and hard-to-reach settings. The OraQuick HCV self-test (HCVST) is the first World Health Organization-prequalified HCVST, which delivers results in 20-40 min via an easy-to-use gum-swab format. Field evaluations report a sensitivity of about 97%–98% and a specificity of about 99%–100% that are comparable with those of blood-based lateral-flow assays (e.g., Alere Truline, SD Bioline). Usability studies demonstrated an acceptability rate of over 90% and a correct self-test completion rate of over 85% in key populations. HCVST with the OraQuick HCVST kit provides a practical, evidence-based approach to closing diagnostic gaps, particularly among underserved or stigmatized populations. To maximize the public health impact, programs should integrate self-testing into national screening algorithms, ensure linkage to RNA confirmation and treatment, and consider economic and operational contexts.

Key Words: Hepatitis; Hepatitis C; Liver diseases; Rapid test; OraQuick hepatitis C virus self-test

Core Tip: The OraQuick hepatitis C virus self-test, designed for home use, offers a profound yet straightforward solution for early detection, empowering individuals to take charge of their health and bringing us closer to the goal of hepatitis C virus eradication.

TO THE EDITOR

Hepatitis C virus (HCV) is an RNA-enveloped virus that primarily infects human hepatocytes[1]. It has a disease burden of 58 million people worldwide, and only 20% have been diagnosed[2]. Most individuals infected with HCV do not present acutely; they progress to chronic liver disease, which manifests as cirrhosis, portal hypertension, hepatocellular carcinoma, and hepatic encephalopathy. The transition from acute HCV infection to chronic liver disease is subclinical[3]. Timely detection of HCV infection is crucial for improving clinical outcomes and reducing the global financial burden of the disease[4].

Despite significant advancements in treatment, diagnosis remains a barrier, particularly in resource-limited settings. Traditional diagnostic methods necessitate laboratory infrastructure and trained personnel, limiting accessibility in many parts of the world. The advent of self-testing kits represents a pivotal advancement in diagnostic accessibility and patient empowerment, bridging this gap[5]. Previously, HCV diagnostic tests included enzyme immunoassays and nucleic acid tests. Although accurate, these methods are not ideal for widespread screening due to their high cost and limited accessibility in resource-limited settings. Point-of-care testing has emerged as a solution for improving accessibility, exemplified by innovations such as the use of Gene X-pert HCV RNA and various rapid diagnostic tests (RDTs). However, these still often require skilled personnel and specialized equipment. Nevertheless, the introduction of the OraQuick HCV self-testing (HCVST) kits, designed for home use, was not available until recently, marking an advancement in HCV detection[6].

PATHOPHYSIOLOGY OF HCV

HCV enters hepatocytes via endocytosis by binding to cell surface coreceptors. Once internalized, the HCV-positive RNA strand is uncoated and released into the host cytoplasm, where it is translated into 10 mature proteins. These mature peptides are cleaved by host proteases and viral-encoded proteases. These peptides are inserted into the endoplasmic reticulum and function as a replication complex, converting positive-strand RNA into negative-strand RNA. The negative strand acts as a template, and then new positive RNA strands are produced. These strands are packaged with the core and glycoprotein envelope, forming mature HCV, which is released via exocytosis[7]. It is not the virus itself that destroys the hepatocytes but rather the slow cellular response of CD4+ and CD8+ cells that leads to hepatic necrosis[8].

HIGH-RISK GROUPS AND EPIDEMIOLOGY

According to the Centers for Disease Control and Prevention, the high-risk population includes people who inject drugs, males who have sex with males, those living with HIV, those who have undergone hemodialysis, blood transfusions, and organ transplantation, infants born to HCV-positive mothers, and health care professionals who are exposed to needle stick injuries and sharp and mucosal exposures[9]. According to the World Health Organization (WHO), approximately 58 million people are living with HCV infection globally (Figure 1). The Eastern Mediterranean Region bears the largest share of chronic HCV infections (12 million), followed by 9 million each in Southeast Asia and Europe, 7 million in the Western Pacific, 8 million in Africa, and 5 million in the Americas[2].

Figure 1 Epidemiological distribution of hepatitis C virus-affected people across the World Health Organization. HCV: Hepatitis C virus.

DIAGNOSTIC CHALLENGES

The diagnosis of current HCV infection is based on two phases: Screening and confirmatory testing. Screening includes ELISA or rapid tests, followed by confirmatory testing, such as a nucleic acid tests for HCV RNA (viral load)[10,11]. Although these antibody assays are sensitive and specific, their limited accessibility and acceptability make the diagnosis and treatment of HCV hard in low-income countries. Moreover, false-positive tests lead to unnecessary confirmatory HCV RNA testing. These standard RNA confirmatory tests are expensive and complex and can only be performed in centralized laboratories[12]. The WHO aims to detect 90% of people living with HCV by 2030. This goal can only be achieved using rapid, readily available, and acceptable tests[13,14]. The comparison of HCV diagnostic methods is well summarized in Table 1.

Table 1 Comparison of hepatitis C virus diagnostic methods.

Diagnostic method	Sample type	Turnaround time	Sensitivity/specificity	Equipment required	User level	Advantages	Disadvantages
Enzyme immunoassay	Serum or plasma	1–5 days	95%-99%/98%-99%	Lab equipment, trained staff	Laboratory professionals	High accuracy; standard for screening	Requires lab setup; not suitable for remote areas
Nucleic acid test	Serum or plasma	1–7 days	> 99%/> 99%	Advanced lab instruments	Laboratory professionals	Confirms active infection; gold standard	High cost; requires infrastructure
GeneXpert HCV RNA	Plasma or serum	About 1 h	99%/99%	Portable cartridge-based system	Trained healthcare workers	Fast, decentralized testing	Expensive; less available in rural settings
OraQuick HCV self-test	Fingerstick or venous blood	About 20 min	98%/100%	None	Layperson (self-testing)	Easy to use; no lab needed; WHO prequalified	Detects antibodies only; follow-up NAT needed

HCV: Hepatitis C virus; WHO: World Health Organization; NAT: Nucleic acid test.

RDT

RDTs can quickly detect infections. These tests provide results in 20-40 min, facilitating timely medical decisions and do not require additional infrastructure. The rapid nature of these tests helps bridge the gap between diagnosis and healthcare access, especially in underserved populations. A range of rapid HCV diagnostics tests is available. Table 2 summarizes the key characteristics of the OraQuick HCVST and other point-of-care assays. Rapid diagnostic tests, such as the OraQuick HCVST and other standard tests, including the AlereTruline HCV rapid test and the Abbott SD Bioline HCV test, achieve high accuracy in antibody detection[15,16].

Table 2 Comparison of the OraQuick hepatitis C virus self-test and other point-of-care tests.

Test	Type	Sample	Target	Sensitivity	Specificity	Time	Setting
OraQuick HCV self-test	Rapid Ab	Oral fluid	Anti-HCV Ab	97.8%	100%	20 min	Self-test
Alere Truline HCV rapid test	Rapid Ab	Fingerstick blood	Anti-HCV Ab	99.4%	99.7%	15–20 min	Clinic/POC
SD Bioline HCV test	Rapid Ab	Fingerstick blood	Anti-HCV Ab	99.4%	99.7%	15–20 min	Clinic/POC
GeneXpert HCV Viral Load	NAAT (RT-PCR)	Plasma/serum	HCV RNA	100%	98.5%	Approximately 105 min	Decentralized POC
Lab-based HCV ELISA	ELISA	Serum/plasma	Anti-HCV Ab	≥ 99%	≥ 99%	Hours/days	Central lab
Lab-based HCV RNA (PCR)	RT-PCR (quantitative)	Plasma/serum	HCV RNA	Reference standard	Reference standard	Hours–days	Central lab

HCV: Hepatitis C virus; RT-PCR: Reverse transcription PCR; NAAT: Nucleic acid amplification test; POC: Point of care.

RISE OF SELF-TESTING: ORAQUICK HCV

Self-testing is a strategy in which patients collect their samples, perform the test, and interpret the results privately. This approach has revolutionized HIV screening and is now being applied to HCV. In 2021 the WHO recommended the HCVST to complement existing HCV testing services[17]. The first WHO prequalified self-test, the OraQuick HCVST, was approved in mid-2024[18]. This is an immune-chromatographic kit that uses oral mucosal swabs and provides results in 20-40 min[19]. HCVST studies have demonstrated high acceptability. A study in Vietnam found that 90% of the high-risk population had accepted self-testing[20]. A systematic review and meta-analysis by Perazzo et al[21] revealed that the pooled estimates for correct sample collection and people who did not require assistance in any step while performing HCVST were 87.2% and 62.8%, respectively.

The OraQuick HCVST has several prerequisites, including a minimum age of 18 years. The patient should refrain from eating or drinking anything for at least 15 min before the test and from using any usual oral care products for 30 min before the test. The test device of the OraQuick HCVST features a result window that displays a positive result with two red lines at points C and T. In contrast a negative result is indicated by a single line at point C only within the result window. OraSure (parent company) recommends that patients wait 20 min before reading the results and should not read the results after 40 min. This test is relatively easy to use and interpret, requiring only basic education[22].

If an individual tests positive, patients should visit the nearest healthcare setting to evaluate their test results further and discuss possible treatment options. The Centers for Disease Control and Prevention recommends following the algorithm (Figure 2) for managing patients who screen positive on antibody-based screening tests[23].

Figure 2 The Centers for Disease Control and Prevention recommends following the algorithm for managing patients who screen positive on antibody-based screening tests. ¹Hepatitis C virus (HCV) RNA testing or follow-up testing for HCV antibodies is recommended if the patient is exposed to HCV in the prior 6 months. Testing for HCV RNA can be considered for patients who are immune compromised. ²HCV antibody assay can be considered to differentiate false positive from past resolved infection. Also, if clinical evidence of HCV infection is present or patient had exposure to HCV in prior 6 months then HCV RNA should be carried out. HCV: Hepatitis C virus.

IMPLEMENTATION AND POLICY CONSIDERATIONS

The implementation of the OraQuick HCVST at a global scale across middle-income and low-income nations requires careful policy and program planning. A study conducted by NICE and Walker et al[25] concluded that HCVST increases screening, diagnosis, and treatment albeit at a relatively higher cost, ranging from £12 to £15. They emphasized that HCVST is cost-effective in populations with a relatively high prevalence of HCV[24,25]. The WHO emphasizes that prequalification of HCVST ensures safety, quality, and affordability in lower-income and middle-income countries. Moreover, the WHO noted that the availability of the OraQuick HCVST will help achieve the aim of diagnosing 90% of people living with HCV. National programs that aim at increasing the acceptability of HCVST should be initiated in high-prevalence areas. Any reactive self-test must be followed by confirmatory testing, and patients with a positive result should be accurately treated. Emotional and psychological support is essential in achieving these aims.

CONCLUSION

Scaling up HCVST could reach underserved groups and accelerate linkage to care, advancing elimination goals. However, successful implementation will require clear policies, community education, and integration with treatment services to ensure that self-testing is followed by confirmatory diagnosis and cure. Self-testing adds an essential option to the HCV diagnostic arsenal; with thoughtful deployment it can significantly improve early detection and treatment of hepatitis C worldwide.