This systematic review describes characteristics and outcomes of HCV screening programs in the general population, and includes 67 programs. In total, 24 of them were exclusively set up for the purpose of HCV screening, whereas 41 were integrated in already existing health care facilities (not aimed at HCV risk groups), and two programs used both an integrated and nonintegrated approach. Altogether, the programs that were published identified approximately 25,700 HCV-infected individuals. Clearly, large-scale, and long-term screening and referral programs are needed to address the HCV-related burden of disease in an era of potent therapy for HCV.
The programs were highly heterogenic in their organization, recruitment, and screening procedure, and the vast majority did not use a comparison group to assess the effectiveness of their screening program. Hence, we cannot draw firm conclusions as to which screening program strategy, or which program characteristic (e.g., free-of-cost vs. low-cost screening, anonymous vs. nonanonymous screening, use of particular media to promote screening) is more effective than another in attracting or motivating individuals for screening or in attracting those at higher risk for HCV. Screening programs that compare different recruitment and screening strategies are needed to gain insight into effectiveness of strategies and program characteristics.
In addition, many studies did not report program characteristics (e.g., the laboratory tests that were used). The same was true for screening uptake and follow-up data regarding HCV-related care, and even if reported, there was not much consistency (e.g., some reported the SVR rate among those who completed treatment, whereas others reported that treatment was ‘rather successful’). The underreporting and the lack of uniformity of data reporting greatly hinder the comparison of screening programs. Data reporting standards (see Parameters of screening programs) are needed to be able to compare screening program characteristics and outcomes in order to find out which factors are effective. If demonstration projects for HCV screening are not able to demonstrate direct effects in terms of number of individuals who tested positive for HCV that are linked to care, secondary evaluation measures could be used. For instance by monitoring rates of HCV screening and positivity in the hospital or referral laboratory and by comparing these data with data from previous years or from hospitals or laboratories that were not involved in the demonstration project.
In general, we noticed relatively high HCV prevalences in programs that used a prescreening selection based on HCV risk factors (especially in programs that used elevated ALT or a history of IDU as indications for HCV screening) or migrant status, in programs that were carried out in intermediate to high HCV-prevalence countries or regions, and in programs in psychiatric clinics. Also, relatively high HCV prevalences were found in nonintegrated programs in low HCV-prevalence countries that targeted the general population (see Additional file 1: Table S1, row 1–7), even without a prescreening risk assessment. These programs might have screened a self-referred population, and may have attracted those at risk of HCV in the general population, and therefore observed prevalences are higher than those in the general population. For the study by Hayashi etal (see Additional file 1: Table S1), screening was performed in a specific region in Japan with a presumably high HCV prevalence, explaining the very high prevalence that was found. In most studies, a history of IDU was the main risk factor among the identified HCV-infected individuals. In general, low HCV prevalences were found in programs that targeted health care workers, and in programs that were carried out in antenatal clinics. Programs in STD and GP clinics that did not use a prescreening risk selection also found relatively low HCV prevalences.
Only one study reported that the promotion of the screening program was based on theoretical insights or knowledge about determinants facilitating participation in screening programs. None of the studies reported the use of simple tools that may increase the screening uptake, such as reminder messages , or support with planning of when and how to get screened (i.e., creating implementation intentions ). In many studies, and especially those describing nonintegrated programs, the uptake of screening was not reported.
We found that integrated screening programs in general screened a larger number of individuals than did nonintegrated screening programs in low HCV-prevalence countries. Integrated screening programs have three advantages in that they do not have to attract their target population for screening, and they can use a facility that is familiar to the public. In addition, they can facilitate continuous screening and follow-up of individuals at relatively low cost, whereas nonintegrated programs offer screening usually for a limited period. On the other hand, integrated screening programs only reach those who have a reason to visit such facilities (unless media campaigns have been used to attract more people), whereas nonintegrated programs may attract a different risk population that otherwise would not be screened and do not perceive themselves at risk for HCV (i.e., the hidden population). We believe that both approaches are useful and complementary. In addition, since nonintegrated screening in general is more complex to organize, it may be efficient to screen for other diseases simultaneously, when risk groups overlap.
We identified several studies that did not confirm HCV antibody test results. Many of the identified programs targeted asymptomatic individuals in the general population with a relatively low HCV prevalence. In such populations, unconfirmed HCV antibody test results may include 35% (range: 15%–60%) false-positive test results . Hence, the program outcomes that are reported may include a substantial degree of uncertainty, and should be interpreted with care. We like to emphasize that HCV screening programs should use validated screening methods, and describe the tests that were used when publishing the results of their screening programs.
As for study limitations, the majority of the screening programs that were evaluated in this review occurred in just a few countries (USA, UK, and France), most likely since this review was limited to studies published in English, French, German, Spanish, and Dutch. Therefore, the results may not be generalizable to other (non-Western) countries or countries with a higher HCV prevalence. With respect to publication bias, this review only includes screening programs that were published and programs that were successful in identifying HCV-infected individuals may have been more likely to be published. However, we did identify several programs in which no individuals were diagnosed. Furthermore, as identification of HCV-infected individuals serves a clinical goal and not necessarily a scientific goal, not all screening efforts have been evaluated or published. Our search identified several announcements of HCV screening activities [103, 104] or cost-effectiveness evaluations of screening activities  that did not provide any further information about the screening program and/or outcomes. Further, our review describes several screening programs, but it cannot determine the efficiency and effectiveness of these screening programs in preventing future HCV-related morbidity and mortality. Measuring these effects of HCV screening programs is a challenge because randomized, controlled trials or comparison groups and decades of follow-up time are required. As an alternative method, mathematical modelling studies can be useful to estimate long-term effects of screening programs (e.g., [106, 107]), especially when certain program outcomes (e.g., participation rate, prevalence) are used as parameters in the model. The efficiency and effectiveness of screening also depends on the uptake and outcomes of therapy and other preventive measures that may follow from diagnosis. Efficiency relates to the number needed to be screened to identify a treatable case of HCV. Surprisingly, most studies did not report such data, and merely mentioned that HCV-infected individuals were notified of their test result and referred for clinical care. Following Wilson and Jungners third screening principle , facilities for diagnosis and treatment should be available. This means that the screening program itself is as important as the efforts that are undertaken to bring identified patients into care and have them benefit from preventive measures and/or treatment. Hence, evaluation reports of screening programs should include clinical follow-up and systematically report outcomes.
A recent systematic review by Jones etal on the effectiveness and cost-effectiveness of interventions aimed at raising awareness of and/or increasing engagement in case finding and screening with high-risk groups for HCV and HBV and practitioners included only programs with a comparison group (e.g., randomized controlled trials, pre- and postintervention data, repeated cross-sectional studies) . About half of the studies (12/25) included in that review were aimed at high-risk groups for HCV that are relatively easy to target, such as current IDU and incarcerated individuals, whereas our review includes studies that aimed to identify the hidden population of HCV-infected individuals. Jones etal identified drug services and primary care as settings in which interventions could effectively increase screening uptake. They also found that DBS screening in addition to venipuncture might increase HCV screening uptake in drugs services or prisons. In our review, a few studies reported the use of home collection tests, DBS, or oral fluid tests, but these studies did not demonstrate high screening uptake. Further insight into the effect of alternative noninvasive screening procedures on screening uptake is needed. As in our review, Jones etal concluded that improvement of health outcomes following diagnosis for those identified with chronic HCV deserves careful attention.
In the United States it has recently been recommended that all people born between 1945 and 1965 should be offered a one-time screening without prior risk assessment , since HCV prevalence in this group is four times greater than adults aged 20 years or older who were born outside of the birth cohort, and identifying this group through a high risk profile has been unsuccessful so far. More importantly, this screening strategy is estimated to be cost-effective assuming an uptake of 15% . Although a relatively low uptake of 15% was assumed in the cost-effectiveness model in the USA, those who participate may not be representative for the total population of baby boomers. It may be that those at lower risk for HCV (i.e., the worried-well) could be more likely to respond. Thus, although it may be promising, the effectiveness of such an intervention needs to be demonstrated in practice. Nevertheless, it should be examined whether it is feasible and cost-effective to implement such a birth cohort screening in countries with a lower HCV prevalence.