A scoping review on HCV screening strategies: population to screen and the test types

Abstract

Background

Hepatitis C virus (HCV) is a genetically diverse blood-borne pathogen causing liver inflammation and damage. It is one of the global public health problems responsible for claiming thousands of lives every year. Although there are various HCV testing strategies depending on the specific circumstances and guidance of local authorities, the proportion of diagnosed HCV cases in Low- and Middle-Income Countries (LMICs) is estimated to be less than 5%. This review analyzes and documents evidence for different ways of screening HCV.

Methods

The updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines have been used as the basis for this scoping review. Retrieved articles were screened and extracted by three independent individuals to make sure that all pertinent literatures were included.

Results

A total of 8318 records were retrieved from four electronic databases (Scopus, PubMed, CINAHL and Google Scholar). Of the total retrieved records and after applying the pre-defined inclusion criteria, we included 51 studies in this review. According to the studies included in this review, three major screening approaches were noted: The universal, targeted, and risk-based HCV screening strategies. Population to screen include the baby boomer cohort, pregnant women, key populations, those experiencing homelessness, adults visiting health facilities, employees, and social event attendants. A “one-stop-shop” HCV testing initiative at different settings, such as prisons, addiction rehabilitation centers, and community dropping centers, were found to increase HCV test uptake among key populations. Integrating HCV screening with the existing HIV and Sexually Transmitted Infection (STI) clinics was highlighted to identifying and linking HCV-infected individuals to appropriate care and treatment. Although there are many ways of diagnosing HCV for treatment, identifying those who were reactive for HCV antibody first, followed by an HCV-antigen test for those antibody-positive, were found to be the most cost-efficient way of diagnosing HCV infection.

Conclusion

HCV screening among pregnant women, the baby boomer cohort, adults visiting health facilities, engaging in injection drug use, incarcerated individuals, and those experiencing homelessness are useful approaches in identifying HCV-antibody positive individuals. An efficient way to reach the most at-risk people is to incorporate HCV screening into community service centers and clinics.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12889-025-23809-7.

Introduction

Hepatitis C virus (HCV) is a highly genetically heterogenous blood borne pathogen that is responsible for acute and chronic hepatitis. It causes liver inflammation, sometimes leading to serious liver damage, including cirrhosis and risk of hepatocellular carcinomas [1]. The HCV spreads mainly through contaminated blood [2]. However, other multiple modes of transmission such as iatrogenic transmission (resulting from medical procedures), intravenous drug use and sexual transmission were reported to contribute to the spread of the virus. HCV is among the global public health challenges with an estimated 50 million people living with chronic disease, with approximately 1 million new cases emerging each year. In 2022, the World Health Organization (WHO) reported that HCV caused about 242,000 deaths worldwide, mostly resulting from severe complications like cirrhosis and primary liver cancer [3]. Sub-Saharan Africa is known for having a notably high prevalence of HCV, with an approximate overall rate of 5.3% [4]. In the region, multiple modes of transmission such as iatrogenic transmission (resulting from medical procedures), intravenous drug use and sexual transmission were reported to contribute to the spread of the virus [4]. When examining specific regions within the region, the central African region stands out with the highest estimated prevalence of 6%, west Africa has an estimated prevalence of 2.4%, while southern and east Africa has the lowest prevalence of 1.6% [4]. For instance, HCV is a public health problem in Ethiopia. The prevalence of HCV (based on antibody test) in the general population is estimated to range from 0 to 22% with a pooled estimate of 2%, and higher rates (4%) reported among HIV patients [5].

In 2019, it is estimated that less than a quarter of all individuals with chronic HCV infections were tested while the rest have remained undiagnosed, and not accessing appropriate treatment [6]. The proportion of diagnosed HCV-antibody positive cases in Low- and Middle-Income Countries (LMICs) is estimated to be less than 5%. This could be attributed to lack or weak hepatitis C surveillance programs to inform the regional epidemiology, complex and unaffordable diagnostic algorithms and assays, poor infrastructure and laboratory capacity, use of low-quality test assays and high cost of direct-acting antivirals (DAAs) for those in need, although they have been diagnosed [7]. HCV testing strategies vary depending on the specific circumstances and guidance of local authorities.

According to the Centers for Disease Control and Prevention (CDC) USA, universal screening involves offering HCV testing to all adults at least once in their lifetime and offering testing to pregnant mothers at each pregnancy in settings where the HCV prevalence is greater than 0.1% [8]. The goal of this strategy is to identify individuals who may not be aware of their HCV infection [9, 10]. While universal screening of pregnant women provides an opportunity to treat HCV-positive mothers and reduce vertical transmissions [11], a more efficient approach is risk-based screening of pregnant women [12]. The risk based HCV screening is also recommended for certain groups with elevated risk of acquiring HCV, such as people who engage in injection drug use [13, 14], individuals with a history of blood transfusions [15], healthcare workers with increased exposure [16], and those with high-risk sexual behaviors [17, 18]. HCV testing may also be recommended for individuals receiving healthcare services, including those with unexplained liver disease, elevated liver enzyme levels, or individuals who are candidates for certain medical procedures like organ transplantation and hemodialysis [19].

The above-mentioned screening strategies provide the basis for selecting efficient ways of screening and treatment options that help reduce the transmission risks associated with HCV. However, it is important to note that although there are multiple HCV screening options, there is lack of synthesized evidence regarding their implementation in different settings. Hence, this review aims to systematically organize key concepts on the overall HCV screening strategies. There is a key tension between a “screen all strategy”, which has a high cost of diagnosis and high opportunity cost especially in low prevalence settings verses a “risk-based strategy” with lower costs but an exclusion of a minority of those infected from diagnosis altogether. Ultimately, this scoping review lays the foundation on how best to implement these strategies effectively and reach people from all backgrounds who are at risk of acquiring the virus.

Study objectives

The major objective of this scoping review is to identify and summarize the body of evidence related to the overview of HCV diagnostic strategies.

Specific objectives:

• To summarize the existing HCV testing approaches in terms of identifying HCV infected individuals in different groups and settings.

• To explore and compile the types of tests used for screen HCV.

Methods

This scoping review has been guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines modified for a Scoping review [20]. The following steps were followed to develop the result of review: (i) research questions, (ii) search strategy, (iii) eligibility criterion, (iv) relevant studies, (v) charting the data and (vi) collecting and summarizing the result. The methods have been registered at OSF on October 2, 2023 10.17605/OSF.IO/NPW4C.

Research questions

• What strategies are being used in across various population groups for HCV screening?

• What types of tests are used for screening HCV in different testing contexts?

Search strategy

The articles were identified through electronic data bases such as: Medline/PubMed, CINAHL Scopus libraries and Google Scholar by developing search strategies (appendix 2). We also conducted a hand search, citation tracing and search for relevant grey literature. Boolean operators such as “AND” and “OR” were used with key search terms such as, HCV, Hepatitis C Virus, test, diagnosis, identify, screen, strategy, approach, and implementation. Retrieved articles were screened by three independent individuals to make sure that all pertinent literatures were included. The articles were downloaded to Endnote reference manager to maintain and manage citations, and facilitate the review process. Unpublished documents like reports were searched from The Ethiopian Ministry of Health and the Ethiopian Public Health Institute’s library.

Eligibility criteria

Studies with both qualitative (N = 7) and quantitative (N = 44) data were included in this review. Primary quantitative data of the studies were collected through cross-sectional (N = 21) and longitudinal study designs (N = 7). Studies with secondary record reviews (N = 4) and mathematical modellings (N = 12) were also included. Of those studies that used primary data, five were pilot studies. Data were gathered at a household level (N = 6) and at different facilities (N = 28) including health facilities, rehabilitation, and dropping centers. The rest 17 articles used data from mixed sources for modeling, work place, social event, and people living on street.

In this Scoping Review, we have included all studies conducted on HCV diagnostics from published and unpublished sources. All non-review studies conducted from 2010 to 2023 were included in this scoping review. Furthermore, the inclusion criteria follow the Population, Concepts and Context (PCC) framework described by Joanna Briggs Institute (JBI) [20], shown in Table 1.

Table 1.

Inclusion criteria using population, concepts and context framework (PCC)

Population, Concepts and Context framework (PCC)
Population
HCV diagnosed population of any age group and category in both qualitative and quantitative studies
Concepts
HCV/Hepatitis C Virus
HCV diagnosis/test strategies
Context
All studies conducted in worldwide
Studies done from 2010 to 2023

Exclusion criteria

• HCV diagnosis in non-human

• Systematic reviews and meta-analysis

• Any context other than HCV diagnosis

• Studies conducted before 2010

• Studies and reports in other languages than English and Amharic

Relevant studies

A structured and systematic search strategies were developed to identify relevant studies from different databases. Once the articles were identified, title and abstracts were reviewed by three independent experts to identify relevant studies. Disagreement between two reviewers were resolved by discussion among independent reviewers. We have used a comprehensive data extraction checklist to collect important information from the studies. Data were extracted on the study population, location/region of study, study design, outcomes, method of diagnosis and results.

Data collection, charting and, quality assessment

Data was extracted by two experts (SA and GF) using a standardized data extraction checklist on Microsoft excel. Endnote was used to combine search results from databases and to remove duplicate articles initially. Then, relevant studies were screened by their titles and abstracts. The data extraction checklist included author name, year of publication, region (an area where studies were conducted), study design, study type, diagnostic method used, type of sample used, type of test used, population group, sample size, and the number of participants with HCV. The tool was piloted and refined before the actual use. A draft data extraction checklist to collect important information from the studies was developed based on the review objectives and eligibility criteria (Appendix 1). The checklist was pre-tested on a purposive sample of studies to ensure its clarity, relevance, and comprehensiveness. Two independent reviewers piloted the tool by extracting data from this sample, after which discrepancies and challenges were discussed and resolved. Insights gained from this pre-testing phase informed refinements to the extraction form, including clarification of ambiguous items and addition of missing data fields.

Statistical analysis

Descriptive statistics were used to summarize the characteristics of the selected studies, including geographic locations, and objectives of the studies. To ease the data analysis, and based on the review question, we have defined two sub-categories to classify studies: HCV screening strategies with focus on population to screen, and the laboratory test strategies. Each study included was assigned to either of the categories mentioned. The two groups were further classified based on idea similarities and summarized. This analysis has enabled us to providing valuable insights into the current landscape of HCV screening strategies.

Ethics statement

Ethical approval was not required.

Results

A total of 8318 records were retrieved from four electronic databases. We identified 5167 records in Scopus, 2871 in PubMed, 46 in CINAHL and 234 in Google scholar (Fig. 1).

Fig. 1.

Flowchart of study selection

Of the total 51 studies included in this review, forty of them focus on the efficiency in terms of identifying HCV positives and feasibility of screening HCV in various population groups, while 11 studies examine the effectiveness of different laboratory test strategies in linking patients to care. Of the 40 studies that emphasize which population group to test, four approaches were identified. These include universal HCV screening, HCV screening among key populations, HCV screening among health care seekers, and HCV screening among employees and social event attendants (Appendix 3).

Studies in this review were conducted in almost all regions of the world. The majority of the articles, 17 (33%), are from the USA and 15 (29%) are from Europe. Only two studies conducted in Africa were identified and included. Both the articles were from Egypt. See more in Table 2 below.

Table 2.

Geographic distribution of articles included in the review (N = 51)

Sr. No	Regions	Number	Percent
1	USA	17	33%
2	Europe	15	29%
3	Asia	8	16%
4	Australia	5	10%
5	South America	4	8%
6	Africa	2	4%

Universal screening

The universal screening strategy is further classified as screening among pregnant women, screening among adults over 40 years and birth cohorts, and screening among the general adult population over 18 years old.

Universal screening in pregnant women

Six studies from the USA, the Netherlands, Australia, and Egypt examine the reliability and cost effectiveness of universal screening in pregnant women in contrast to risk-based screening. All the articles summarizes that Universal screening for hepatitis C in pregnant women is more reliable and cost-effective than risk-based screening [21–26], even when the prevalence of HCV is low [24]. Although the majority of women who test positive for HCV antibodies have identifiable risk factors, it is important to note that there is a small number who may not be detected if a risk-based screening approach is utilized [21, 25]. Also, inconsistency in identifying risk factors, and HCV infection among women who did not have any known risk factors were observed [26].

Universal screening in baby boomer and above 40 years

Seven studies conducted in Korea, Canada, Norway, the USA, China, and Brazil have evaluated the strategy to identify HCV among baby boomers (N = 3) and all adults above 40 years old (N = 4). Three studies show that the prevalence of HCV antibody in the baby boomer cohort is high [27–29]. The reactive antibody was higher in those who were born between 1945 and 1965 than in those born in other years and in the general population. However, a substantial number is missed when focused on the birth cohort and risk factors [27, 29]. In Korea [30] and China [31], HCV screening in population older than 40 years was found to be highly cost-effective. However, this strategy was found to be inefficient as it missed as many as 39% of HCV-positive individuals in Norway [32]. It was also reported to have no difference in reaching the HCV-exposed population in Brazil [33].

Universal screening among all adult population

Studies from USA and United Kingdom highlight a high prevalence of HCV infection among adult patients visiting emergency departments [34–36]. The study in London identified a relatively lower HCV prevalence of 2% among emergency department visitors while the studies in New York and California have shown 6% and 16% (on average) HCV prevalence in similar setting, respectively. Prior selection of patients to be screened and use of an electronic alert system to remind test orders has contributed to the high rate of detecting HCV-infected adults [34, 36]. Two community-based pilot studies conducted in Georgia and Spain have shown that HCV screening in the household level is feasible and is an essential approach to increasing test uptake and linkage to the care of patients who are not aware of their infection [37, 38]. The studies have reported the community-based HCV prevalence of 3.6% in Georgia in 2022 and 1.14% in Spain in 2018. In addition, a model-based analysis that compared the cost effectiveness of different HCV screening strategies suggested that screening the entire population in the USA and linking it to care is projected to be cost saving in the long run [39].

Screening among Key populations and those experiencing homelessness

A total of 10 studies from the UK, USA, China, Italy, Iran, and Nepal that evaluated HCV screening strategies among key populations and the those experiencing homelessness were identified. Three were on people who engage in injection drug useand other engaging in non- injection drug use, three on incarcerated individuals and those under community supervision, two on men who have sex with men (MSM), and another two experiencing homelessness. Studies on PWID and other engaging in non- injection drug usewere conducted in rehabilitation and drop-in centers. The highest HCV prevalence among PWID was seen in Iran (47.1%) [40] while the lowest was seen in the study conducted in Ohio, USA [41]. All the studies among engaging drug useshow the feasibility of integrating the screening program with the prevention centers and are efficient to screen HCV with a high HCV yield [40–42]. Two studies were conducted in prison settings in Italy [43] and Iran [44]. Each study enrolled over 1800 incarcerated individuals, and the HCV positive yield was more than 5% in the total enrolled. A study among individuals under community supervision in the USA also showed a high HCV yield of 18% and improved linkage to care [45].

Two studies have assessed the cost-effectiveness of HCV screening in HIV-negative MSM and the use of the individuals level HCV self-tests. According to these studies, HCV screening among HIV-negative pre-exposure prophylaxis (PrEP) users is effective in the UK [46] and self-testing is claimed to be cheaper than the standard HCV screening in China [47]. Studies conducted among those experiencing homelessness emphasis the need for community-based HCV screening among those experiencing homelessness [48, 49]. A hospital-based screening is inadequate in identifying and linking HCV-positive those experiencing homelessness [49]. Besides, community-based screening in this group is an efficacious and simple approach to counselling, testing, and treating those in need [48].

Screening among health care seekers at different health service outlets

Seven studies in the USA and Europe have evaluated HCV screening implementation among health care seekers at different clinics and hospitals. Integrating HCV screening with the existing HIV and STI clinics has been assessed to be effective in identifying and linking HCV-infected individuals [50–52]. A higher prevalence rate than national estimates was observed in outpatient emergency department and pharmacy visitors with potential HCV exposure such as injection drug use and undergoing routine phlebotomy [53–55]. A one-time HCV screening of newly admitted patients to the gastroenterology service identified a high yield of HCV, especially in the baby boomer cohort and engaging in injection drug use [27]. Similarly, a screening among patients presenting for first chemotherapy shows high HCV prevalence, and a risk-based screening would have missed 5% of patients with anti-HCV [56].

Screening among employees and social event attendants

A pilot study in Japan shows that workplace HCV screening of employees helps detect new HCV positives, referrals for treatment, and follow-up [57]. Another approach to HCV screening in Florida, USA was to provide HCV screening to cultural state fair attendants. Although the respondent rate is low, HCV prevalence among the state fair attendants was 4.4% [58].

One study from LMIC, Egypt, emphasizes that HCV screening in high-risk populations is cost-effective. However, screening in the general population is considered a cost-saving strategy [59]. Similarly, a study from Malaysia suggests a stepwise HCV screening strategy, screening a high-risk population first, followed by the general population. This helps buy time to mobilize the investment necessary for universal screening [60].

The HCV screening strategies in this review were ranked based on their efficiency in terms of identifying HCV positives. The most efficient strategy across all articles in the review involved screening key populations and those experiencing homelessness, with an 86% HCV positivity rate among those experiencing homelessness in Los Angeles in 2019 [48], followed by 47.1% HCV positives among Persons Who Inject Drugs (PWIDs) in Iran [61]. The second efficient strategy identified was universal screening among baby boomer and adult populations, showing a 23% HCV rate in patients aged 18 years and born after 1945 in a level I trauma center in North California [36]. However, this strategy identified a lower rate of HCV (0.7%) among baby boomer in Canada [62], and adult population in Spain (1.14%) [63]. The third efficient strategy was screening among health care seekers at various health service outlets, revealing a 16.3% HCV rate among patients at a Sexually Transmitted Disease (STD) clinic in North Carolina [50]. Screening HCV among health care seekers at emergency department in Denmark shows a lower rate of 0.8% [53]. On the other hand, the least efficient strategy was universal screening among pregnant women, with the highest HCV positivity rate among pregnant women being 4.2% in Egypt [25].

Laboratory test strategies

HCV testing points

Six studies from Australia, Canada, and Spain have demonstrated the significant role of point-of-care testing as part of the HCV elimination plan in linking individuals to treatment. A one-stop-shop HCV testing initiative at different settings, such as prisons, addiction rehabilitation centers, and community clinics, increases HCV test uptake and reduces time to link those individuals infected for treatment [64–67]. For instance, a randomized controlled pilot study in Singapore shows that point of care testing of HCV using rapid test along with education and direct referral for treatment in residential areas has increased the odds of HCV treatment initiation by 9.13 [64]. In addition, the use of HCV reflex testing further enhances this strategy by reducing sample contamination levels and streamlining the diagnosis process [68, 69].

Test type and order

Regarding the choice of tests, five studies from Australia, Georgia, Vietnam, and Spain reported the validity and efficiency of different combination of tests to diagnose active HCV infection for treatment. The studies compared the antigen-antibody test (Ag-Ab), the antigen-antibody-viral load test (Ag-Ab-VL), and the antibody-viral load test (Ab-VL). The performance and effectiveness of HCV core antigen test (HCV-core Ag), and HCV antibody test (HCV-Ab) were also evaluated. Among these strategies, the Ab-Ag approach was found to be the most cost-efficient way of diagnosing HCV infection [70, 71]. Furthermore, cost-effectiveness of the combined HCV Ab and Ag test increases when the prevalence of HCV in the tested population is above 1% [72, 73]. Lastly, while both HCV-Ab and HCV-core Ag tests exhibit similar specificity, the HCV-core Ag test demonstrates higher sensitivity than the HCV-Ab test. HCV-core Ag test is also less labor-intensive and has a higher level of accuracy in patients with lower viral loads. This makes it a cost-effective test for low-resourced settings [74].

Discussions

One of the main findings in this review is that, compared to risk-based HCV screening, universal screening is more dependable and economical for all pregnant women. Screening HCV among key populations and those experiencing homelessness, universal screening of the baby boomer cohort and adults, and screening among adults seeking health care services yields a high number of HCV-positives. Regarding where to locate individuals for screening, testing for HCV at households, workplaces, and cultural events is both practical and vital for increasing the number of people tested. Furthermore, coordinating HCV testing initiatives at different settings, such as prisons, addiction rehabilitation centers, and community dropping centers, increases HCV test uptake among key populations. Integrating HCV screening with the existing HIV and STI clinics has been assessed to be effective in detecting and linking HCV-infected individuals to appropriate care and treatment. Although there are many ways of screening HCV, identifying individuals who are reactive for HCV-antibody first, followed by an HCV-antigen test for those antibody-positive, is the most cost-efficient way of diagnosing HCV infection.

According to this review, universal HCV screening among pregnant women irrespective of their risk exposure, is crucial to early detection of HCV infection. This allows for the appropriate medical follow-up and counselling, including determining the need for antiviral therapy following delivery [75]. Besides, risk-based HCV screening misses a substantial number of HCV-infected pregnant women, which could lead to a missed opportunity to prevent mother-to-child transmission of the virus [21–26]. This could be associated with the fact that mothers may not know the risk factors that might have exposed them to the infection or remember their exposure to specific risk factors. Some mothers may not report their risk of exposure to HCV because there may be stigma associated with it. Hence, they are less likely to report their risk exposure and request HCV test. In line with this, the Center for Disease Control and Prevention (CDC) recommends testing all pregnant mothers for HCV at every pregnancy in settings where the active HCV prevalence is greater than 0.1% [76].

Our review highlights that progressively expanding HCV screening in the general population permits a stepwise increase in efforts while maintaining cost-effectiveness. Initially targeting higher-risk populations within the general population can optimize the use of limited resources, and focus on those who are more likely to have the infection [60]. Targeting on these groups ensures that more positive cases are identified and treated [77]. Early identification of HCV cases in high-risk groups allows early intervention including education, counseling, and prompt initiation of antiviral therapy [78]. Treating HCV at an early stage can lead to better outcomes, reducing liver damage, liver cancer risk, and the need for transplantations [79]. Starting with high-risk groups also enables healthcare providers to establish partnerships with community organizations, outreach programs, and support groups [80]. This collaborative approach can help raise awareness, reduce stigma, and improve screening and treatment uptake among the general population [81].

Many articles in this review show the high rate of HCV infection among baby boomers and older adults over 40 years. This high rate of HCV among the baby boomers and older adults could be related to HCV exposure prior to the virus’s discovery or implementation of preventive measures [82]. The other articles in this review demonstrate that compared to the general populations, HCV-positive yield is higher among those who engage in injection drug use, incarcerated individuals, and those experiencing homelessness. This could be associated with practice of sharing contaminated needles and lower access to prevention interventions [83, 84]. Routine HCV screening among these populations helps identify infected individuals who may not have been previously diagnosed, and provides an opportunity for treatment to cure them reducing complications from the disease at the later age [85]. It also reduces HCV transmission among PWIDs, those experiencing homelessness, incarcerated individuals, and the broader community upon their release [86].

This scoping review also indicates that integrating HCV screening at different settings and with different services like HIV and STIs increases the HCV test uptake and reduces missed opportunities among key populations. These settings often serve populations that are at higher risk for HCV infection, such as people who inject drugs (PWID) or those with a history of incarceration [87]. By integrating HCV screening with the services, they already access, it becomes easier to identify and reach those who may be unaware of their HCV status [88, 89]. Many individuals feel uncomfortable seeking HCV testing due to the stigma associated with the disease. Such service integration helps normalize the process and reduce stigma by offering a familiar and non-judgmental environment for them to get tested [81]. It also minimizes potential impediments to HCV testing, such as transportation issues and time constraints [81]. This also promotes a holistic and comprehensive approach to healthcare utilization. It enables collaboration between various health care providers and increases the likelihood of individuals to receive the necessary education and awareness about HCV and follow-up care if an HCV infection is detected, promoting continuity of care [90]. To further overcome the stigma and distance related challenges related to HCV test uptake, The World Health Organization (WHO) endorsed the first pre-qualified HCV antibody self-test [91].

The review on HCV screening strategies emphasizes the effectiveness of different methods for detecting HCV infections in individuals. The most efficient approach, regardless of the study’s location, was found to be targeting key populations and those experiencing homelessness for screening. While universal screening across various demographics such as adults, baby boomers, and healthcare seekers has proven benefits in detecting a high number of HCV cases, it may lead to a lower HCV rates when compared to the general population in certain countries. For instance, the screening of baby boomers and adult population in North California revealed a high prevalence of HCV [36]. Conversely, when screening baby boomers in Canada, a lower rate of HCV (0.7%) was identified compared to the overall national prevalence of 1.03% in the same year [92]. Similarly, while screening healthcare seekers is effective in identifying many HCV-positive individuals, screening at an emergency department in Denmark showed a lower HCV rate (0.8%) [53] compared to the HCV prevalence in the general population of the country (2.6%) [93]. This indicates that customizing screening approaches for different populations can improve the effectiveness of detecting HCV. Nevertheless, it is crucial to consider additional elements when choosing screening methods, particularly factors specific to the country’s HCV epidemiology.

According to our analysis, although there are several HCV screening algorithms available, the most cost-effective technique to diagnose HCV infection is to first establish which individuals are reactive for HCV antibodies, and then test those antibody positives for HCV antigen. In resource-limited settings and during mass screening with large number of sample, pooling samples for HCV antibody screening further boosts the methods’ effectiveness offering substantial cost reduction without sacrificing accuracy [94, 95]. The use of antibody test as the first test is cost-effective because the majority of individuals who are HCV antibody-reactive do not have an active HCV infection, and hence do not need treatment [96]. By identifying HCV antibody-reactive individuals, we narrow down the pool for further testing of those who may potentially have an active infection and need treatment. HCV antibody tests have high sensitivity and specificity, meaning they can accurately detect the presence of HCV antibodies. However, they cannot differentiate between active infection and past exposure [97] as it cannot be used to monitor treatment response. By conducting HCV antigen tests on individuals who are antibody-positive, we can determine if the virus is actively replicating within their system, indicating an active HCV infection [98] which is foundation to monitor the treatment effectiveness. By focusing on individuals who are HCV antigen-positive, healthcare professionals can provide appropriate interventions such as antiviral therapy and lifestyle modifications to prevent disease progression and transmission [99]. This sequential testing approach may help optimizing resources and reducing unnecessary treatment in individuals without active HCV infection. In order to prevent the loss of patients who test positive for anti-HCV antibodies without receiving a confirmatory test, it is recommended to perform both tests using a venous blood sample or a dried blood sample [DBS] sampling method with multiple spots taken from the same blood sample (reflex testing) [100]. This eliminates follow-up visits, reduces diagnosis-to-treatment time from weeks to days, and supports WHO elimination goals [85]. Relatively low-cost, time-saving and easy-to-operate HCV core antigen assays are also emerging to be used as an alternative test for the HCV antigen test [101]. HCV core antigen assays are useful for fast turnaround time for results and monitoring treatment response due to their correlation with HCV Ribonucleic acid (RNA) levels [102]. It is a preferred screening assay for HCV infection in resource-limited settings where polymerase chain reaction (PCR) may not be readily available for monitoring treatment response in patients undergoing HCV treatment [103]. PCR test on another hand is a highly sensitive and specific test that can detect very low levels of viral RNA, hence considered as the gold standard for diagnosing and monitoring HCV infection [104]. It is widely used when high sensitivity is required, such as in patients with suspected early-stage infection or those with very low viral loads [105]. The choice between HCV core antigen and PCR tests depends on the specific clinical scenario and available resources. It is also important to note that specific testing strategies may vary depending on the context, HCV prevalence and availability of resources.

The strength of this review is that it provides a comprehensive understanding of HCV screening strategies. We have mapped out the existing literature systematically. We also believe that our search is exhaustive. It can be used as a reference by researchers who intend to explore a broad question related to the screening strategies. However, this study has some limitations. We encountered a limited number of articles addressing HCV screening strategies in LMICs, particularly within Africa. Additionally, the review was restricted to studies published in English and Amharic, which may have resulted in the exclusion of relevant evidence available in other languages. We also limited our inclusion to studies published after 2010, potentially introducing selection bias, and excluded systematic reviews and meta-analyses, which may have further restricted access to comprehensive information. Therefore, readers should interpret the findings with these limitations in mind. Given these gaps, we recommend further research focused on HCV screening strategies in LMICs to strengthen the evidence base.

Conclusion

HCV screening among pregnant women, the baby boomer cohort, adults visiting health facilities, those who engage in injection drug use, incarcerated individuals, and those experiencing homelessness is effective in identifying HCV-positive individuals. Screening in the general public is cost-effective in the long run due to early detection leading to timely treatment, preventing disease progression and related costly complications. One efficient way to reach the most at-risk people is to incorporate HCV screening into community service centers and clinics. HCV-antibody test followed by HCV-antigen test algorithm is an effective approach to diagnose HCV for treatment and care. HCV antibody testing is commonly used for initial screening, while PCR testing is preferred to confirm active infection and monitoring treatment response.

Author contributions

SA, SI, DW and JD have developed the review idea, the review question and the method of the review. They also revised the manuscript. SA and GF have extracted relevant studies and data, and analyzed the findings. SA drafted the manuscript. AR has supervised the review process and edited both the protocol and the manuscript. ZK, AK, AM, and WA guided the review process and revised the manuscript.

Funding

This research was funded by the National Institute for Health and Care Research (NIHR) (133208) using UK international development funding from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK government.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.