Hepatitis C Virus (HCV) infection is a major public health problem, since approximatively 58 million individuals have been living with chronic hepatitis C worldwide.1 The HCV cascade of care remains unsatisfactory in many countries, especially due to a relatively low rates of facility-based HCV testing and to several barriers from screening to HCV treatment.2 Additionally, the number of people tested for HCV infection dramatically decreased in 2020/2021 due to the COVID-19 pandemic, resulting in a reduction in the number of HCV treatment started. Hepatitis Elimination Programmes in several countries were disrupted due to lockdowns combined with over-burdened healthcare systems during the pandemic.3

Self-testing is an innovative strategy in which people can collect their own specimen and perform a test themselves. Currently, HIV self-testing (HIVST) has been recommended by the World Health Organization (WHO) as an alternative for HIV testing in several countries.4 Similarly, HCV Self-Testing (HCVST) can be a strategy to scale up HCV testing and population knowledge about their need to seek for specific care. WHO has been recommending HCVST as an additional approach to facility-based HCV testing. However, this WHO guidance suggests that use of HCVST should be adapted to local context and that this approach must be followed by HCV infection confirmation (HCV-RNA) and linkage-to-treatment.5 Recently, the first oral fluid HCVST test was pre-qualified by WHO (https://www.who.int/news/item/10–07–2024-who-prequalifies-the-first-self-test-for-hepatitis-c-virus). However, few studies have evaluated feasibility of HCVST, especially in large sample size of general population from Western countries. This study aimed to evaluate acceptability, usability, re-reading/re-testing agreement and participant’s perspectives post-HCVST among health-facility users in the Primary Care System in Rio de Janeiro (Brazil).

From 945 subjects who were seeking for finger-prick HCV RT during the study period, a total of 688 participants agreed to perform HCVST. Three participants were excluded due to eating or drinking 15 min before HCVST (Fig. 1). Therefore, 685 participants (74% female; median age of 52 [IQR 39‒61] years; 75% with self-report brown/mixed or black skin colour, 52.4% with schooling ≤ 10-years and 37.8% were unemployed) were included (Fig. 1). A total of 17.7% (n = 121) had type-2 diabetes and 41.9% (n = 287) had blood hypertension. Regarding risk factors for HCV infection, 6.1% (n = 42) had previous blood transfusion; 27.3% (n = 187) had tattoo or piercing and only 1.0% (n = 7) were People Who Inject Drugs (PWID). Additionally, the sexual risk of HCV transmission was low in this sample: 41.3% (n = 283) reported that they did not have sex 6 months prior to HCVST and those who had sex, 95.5% (n = 384/402) had 1‒2 sexual partners. Table 1 describes the socio-demographic characteristics of included participants. People who agreed to participate in the study (n = 688) were younger (age = 52 [IQR 39‒61] vs. 54 [44‒63], p = 0.028) and had a higher proportion of people with more than 10-years of schooling (47.2% vs. 32.7%, p < 0.001] compared to those who did not agree (n = 257) (Supplementary Table 1).

Fig. 1.

Flow-chart of study.

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Post-testing perspectives

In post-testing analyses, most people felt safe performing HCVST 93% (95% CI 91‒95) and most people would be willing to recommend HCVST for a parent, a friend, or a sexual partner 99% (95% CI 99‒100) and would be willing to repeat HCVST 99% (95% CI 98‒99). However, 41% (95% CI 37‒45) would not perform blood-based HCVST (Fig. 2A). Participants reported that the main advantages of HCVST would be the easiness (93%), the convenience (30%) or the privacy (29%) of HCVST. People reported that interpreting HCVST result was mostly easy 70% (95% CI 67‒73) or very-easy 23% (95% CI 20‒26). Additionally, 73% (95% CI 70‒77) and 24% (95% CI 21‒27) reported that the overall experience of HCVST was easy or very-easy, respectively (Fig. 2B).

Fig. 2.

Overall participant’s perspectives post-HCV self-testing (A) and perception of difficult for reading results and performing HCVST (B).

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This study highlighted the feasibility and re-reading/re-testing agreement of HCVST using oral-fluid kits in general population. Additionally, HCVST was very well accepted for HCV testing by participants from the Primary Care System from Rio de Janeiro (Brazil). Our findings have implications for validating HCVST as an useful tool to scale up HCV testing in strategies targeting the (micro) elimination of HCV by 2030.7

Few studies with limited sample size have described the acceptability and usability of HCVST using OraQuick® HCV Rapid Antibody Test. Those studies included mostly key populations and were conducted in different countries: people with chronic liver disease (n = 95) from USA,8 general population from Egypt (n = 116),9 PWID (n = 150) from Kenya,10 Men who have Sex with mMen (MSM) from China11 and MSM and/or PWID from Vietnam (n = 104 MSM and n = 105 PWID),12 and Georgia (n = 100 MSM and n = 100 PWID).13 A recent systematic review and meta-analysis that pooled data from those previous studies reported relatively high estimates for the usability and re-reading/re-testing agreement of oral fluid HCVST. Briefly, in this review the pooled proportion of people who correctly collected oral fluid sample collection was 87.2% (95% CI 76.0‒95.3) and the pooled proportion of people who performed HCVST without needing assistance in any step was 62.6% (95% CI 37.2‒84.8). Additionally, the pooled rate (95% CI) of re-reading 95.0% (91.5‒97.6) and re-testing agreement (94.4% [90.3‒97.5]) were high. Finally, most people would be willing to test again (pooled = 92.6% [95% CI 86.7‒97.0]) and would recommend HCVST to a friend/relative or sexual partner (pooled rate = 94.4% [95% CI 84.7‒99.6]).14 Most findings of the present study conducted in a large sample size among Primary Care System users in Brazil are aligned with the results from this previous systematic review/meta-analysis. We observed a similar proportion of people who needs assistance for self-testing, high rates of re-reading and re-testing agreement and high acceptance in post-testing questionnaires. On the other hand, we reported a higher proportion of people who incorrectly collected oral fluid sample 32.8% (95% CI 29.4‒36.5). This might be explained by the fact that most studies included in the systematic review were performed in key population who are more used to perform HIV self-testing than people attending the Primary Care System. Despite this relatively high proportion of incorrect sample collection and the need of assistance in our study, we observed a high re-reading and re-testing concordance for oral fluid HCV test.

In the present study, we observed that 41% (95% CI 37‒45) of participants would not perform blood based HCVST. Similarly, pooled data from the systematic review reported that 66.4% (95% CI 60.5‒72.1) would prefer oral-fluid rather than blood-based HCVST.14 Data on acceptability and usability of blood-based HCVST remain scare. Majam et al. reported a high usability of three HCVST fingerstick prototypes: CareStart® (AccessBio, Inc., Somerset, NJ, USA), SD Bioline® HCV (Abbott Rapid Diagnostics Ltd., Jena, Germany) and First Response® HCV Card Test (Premier Medical Corporation Pvt Ltd., Gujarat, India).15 Additionally, an ongoing protocol is comparing HCVST using an oral-fluid (OraQuick® HCV Rapid Antibody Test) and a blood-based (First Response® HCV) HCVST in key population from Malaysia (NCT04982718) .16

The main hypothesis is that HCVST might increase the number of people tested, diagnosed, and referred for treatment and HCV cure. However, this strategy might have a higher cost compared to the standard-of-care. A controlled-trial conducted in MSM from China reported that HCVST increased HCV testing in 60% to 70% compared to the standard-of-care (community-engaged information and recommendation for facility-based testing). Those authors reported a slightly higher cost of HCVST (US$ 1445 vs. US$ 1309), but a lower cost per person tested (U$ 49.83 vs. US$ 654.52) in MSM without HIV infection when compared to standard-of-care.17 Additionally, a recent Cost-Effectiveness Analysis (CEA) reported that the cost of using HCVST might be extremely variable according to the country/setting and this strategy seems to be more cost-effective in populations with high prevalence of HCV infection.18

Few challenges remain to be addressed for implementing HCVST. Difficulties with instructions and/or collecting samples can be barriers/challenges for self-testing for STIs including HCV infection.19 Videos using artificial intelligence can help to reduce errors. For the present study, we used a video with animations and an IFU printed with high-quality figures approved by the manufacturer. In post-testing survey, most people included in our study classified the IFU as comprehensive (99.5%) and judged that the video helped them to perform HCVST (99.2%). The best type of delivery service of HCVST remains unclear. There are few trials evaluating different types of kits distribution (secondary distributions, postal or peer delivery models) or the use of internet-technologies to uptake HCV testing using HCVST in Georgia (NCT04961723),20 Malaysia (NCT04982718)16 and Pakistan (NCT04971538) .21 A potential concern could be the misuse or harm of HCVST (such as coercive testing, violence or discrimination). Since direct evidence for HCVST remain scare, experts have been supporting the use of indirect evidence from HIV self-testing to support HCVST recommendations.22 Therefore, misuse of HCVST might be low since there were few cases of coercion (n = 4/13,267)23 and n = 0/1,06,324 in large sample studies that assessed misuse of HIV self-testing. Additionally, the WHO HCVST guideline reported that there was no difference in intimate partner violence comparing HIVST to standard testing (RR = 0.92, 95% CI: 0.60–1.12; moderate certainty evidence) .25

The best way to implement HCVST in HCV Elimination Programs must be adapted considering local context. Additionally, the use of this tool to improve the HCV continuum of care must be combined with governmental willing, extensive investment in awareness of HCV infection, community outreach and a well-defined linkage to HCV infection confirmation and access to treatment. In Brazil, people can perform HCV rapid tests in facility-based basic health units, and procedures for HCV care, including HCV viral load and universal access to highly effective direct-acting agents, are available for free as part of the Brazilian Public Health System. Despite the availability of those tools and drugs for free, the HCV cascade of care remains unsatisfactory in Brazil.26 This might be related to barriers from HCV testing to start of treatment but also associated with a high proportion of undiagnosed HCV infection due to an unsatisfactory rate of HCV testing. HCVST can be a useful tool for scale up HCV testing. However, this strategy will not impact in the HCV cascade of care if there is a deficient post-testing service.

Our study has limitations. Firstly, this study might have had a selection bias as people who agreed to participate in the study were younger and had higher schooling than those who did not agree. Additionally, we acknowledge that we included middle-aged women with lower education level rather than general population. However, all consecutive individuals aged 18‒79 years who accepted to have fingerstick HCV RT from July to September 2022 were invited to participate in this study. Additionally, there were no additional significant differences in socio-demographics characteristics between those who agreed compared to those who did not agree to participate in this HCVST study (Supplementary Table 1). Secondly, we acknowledge that this study was conducted in a setting of relatively low prevalence of HCV infection. We mostly recruited aged women with a low sexual risk of HCV infection in our study. However, this reflexes the profile of people attending a primary care health unit of the Brazilian Public Health System.27 Moreover, the aim of this study was to assess the usability of HCVST rather than to evaluate the diagnostic value of HCVST kits or the prevalence of HCV infection. Thirdly, we used OraQuick® HCV Rapid Antibody Test kits for professional use adapted for HCVST. Currently, there is no WHO prequalified HCVST kit in the market. All previous studies also used oral fluid HCV kits approved for health professional testing that were re-packed for self-testing. In the present study HCVST were used as RUO and all participants had fingerstick rapid test HCV SD Bioline® and professional use of OraQuick® HCV Rapid Antibody Test for clinical decision-making. Finally, the lack of a one-to-one in-person demonstration on how to use the HCVST kit by a trained study staff might be considered as a limitation. However, we provided a written/pictorial IFU and a step-by-step video translated into the local language that were approved by the Brazilian Ministry of Health, by local IRBs and by the local representative of kit manufacturer to be used exclusively for this study. Additionally, participants performed HCVST supervised by a healthcare worker. People may have felt embarrassed by the presence of the healthcare worker, and this could have impacted our findings regarding the proportion of errors during the procedure. Further studies might be needed to provide evidence of feasibility of unsupervised oral fluid HCVST.

The main strength was the large sample size included in this study. There is few evidence of usability of HCVST among general population, especially in Western countries. Previous studies that assessed feasibility of oral fluid HCVST have included a limited sample, mostly key populations, from Eastern Europe and Asia-Pacific regions. Additionally, only a single study has evaluated usability of HCVST in 116 participants from the general population from Egypt.9 We evaluated the feasibility of oral fluid HCVST among 685 users of the Primary Care System in Brazil, the largest country in Latin America. Other strengths would be the observation of HCVST procedures by a trained investigator, the performance of a second oral fluid HCV test by a healthcare worker for re-testing agreement and the use of fingerstick HCV RT for clinical decision.

In summary, oral fluid HCVST was very well-accepted, feasible and had high re-reading/re-testing agreement in people attending the Primary Care System in Rio de Janeiro (Brazil). However, challenges in collecting samples and a relatively high proportion of individuals requiring assistance can pose significant barriers to HCVST, particularly in real-world settings. The use of HCVST might be a game changer to increase the number of people tested, especially in countries with hard-to-reach populations. However, health authorities and policy makers from different countries and/or regions would need to evaluate the best way to implement HCVST in their HCV Elimination Programs. Future research, especially evaluation of unsupervised testing, implementation, cost-effectiveness studies and those assessing different types of HCVST distribution, are needed considering local context to support the use of HCVST as a public health strategy.

HCV, Hepatitis C-Virus; HIVST, HIV Self-Testing; WHO, World Health Organization; HCVST, HCV Self-Testing; INI/FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas da Fundação Oswaldo Cruz; SMS/RJ, Secretaria de Saúde do Município do Rio de Janeiro; IRB, Institutional Review Board; RT, Rapid Test; REDCap, Research Electronic Data Capture; IFU, Instructions For Use; RUO, Research Use Only; CI, Confidence Interval; PWID, People Who Inject Drugs; MSM, Men who have Sex with Men; CEA, Cost-Effectiveness Analysis.

The study protocol was approved by the Institutional Review Board (IRB) from INI/FIOCRUZ (IRB 42,225,821.9.1001.5262), and SMS/RJ (IRB 42,225,821.9.3004.5279). All participants signed an informed consent prior to enrollment in this study.

All data from the current study were based on published studies and reported in the manuscript, tables and supplementary material. In addition, data are available upon request to Hugo Perazzo, the corresponding author, from Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro (RJ), Brazil.

This work was supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) [grant number E-26/201.351/2021 and E-26/203.693/2021]; and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 445957/2020-4]. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Hugo Perazzo: Conceptualization, Supervision, Formal analysis, Funding acquisition, Writing – original draft, Writing – review & editing. Cristiane Villela-Nogueira: Data curation, Investigation, Writing – review & editing. Maria K. Gomes: Data curation, Investigation, Writing – review & editing. Andre Daher: Project administration, Data curation, Investigation, Writing – review & editing. Cristiane Siqueira-do-Valle: Project administration, Data curation, Investigation, Writing – review & editing. Ketiuce Zukeram: Project administration, Data curation, Investigation, Writing – review & editing. Ana Cristina G. Ferreira: Supervision, Data curation, Writing – review & editing. Karen Cristine Tonini: Supervision, Data curation, Writing – review & editing. Elton Carlos de Almeida: Supervision, Data curation, Writing – review & editing. Sandra W. Cardoso: Supervision, Data curation, Writing – review & editing. Beatriz Grinsztejn: Conceptualization, Supervision, Investigation, Writing – review & editing. Valdilea G. Veloso: Conceptualization, Supervision, Investigation, Writing – review & editing.