6.5. Summary of the evidence
A systematic review and meta-analysis of the impact and cost–effectiveness of different HCV testing approaches (general population or focused testing) was precluded by the limited number of available studies and because of the heterogeneity of settings and populations studied and outcomes measured. Therefore, a narrative review was undertaken in different settings, alongside consideration of recent systematic reviews of HCV seroprevalence in different populations. The three main testing approaches evaluated were (i) routine testing throughout the entire population; (ii) focused or targeted testing of the highest-risk groups; and (iii) routine testing among specific birth cohorts. The overall quality of evidence was rated as low.
Overall, there were 31 relevant studies based on a previously published systematic review (158) and 12 additional studies identified in an updated search (159–192) (see
Web annex 5.2). The majority of studies were from Europe or the US, and very few from LMICs. Fourteen studies evaluated testing in the general population (125, 159–171); 13 in PWID and STD clinics (174–177, 179–181); three in recipients of blood transfusions (160, 161, 182); one among HIV-infected MSM (183); two among pregnant women (184, 185), and two in other populations (186, 187).
Focused testing. Focused testing of PWID, people in prisons or closed settings and HIV-infected MSM was shown to be cost-effective in all settings (159, 176, 180, 183, 188). This was the case among PWID even when the studies assumed poor follow-up rates, limited access to therapy (159, 180) and a high risk of reinfection. The higher the treatment rates, the greater the population impact, and the more cost–effective HCV case-finding becomes (189). Among prisoners, targeting testing to those prisoners with a history of injection drug use further improved cost–effectiveness (176). Among HIV-positive MSM population (183), cost–effectiveness was dependent on appropriate linkage to effective therapy and retention in care.
“Birth-cohort” testing. Most countries have at least some component of a “birth cohort” HCV epidemic (i.e. of easily identified age or demographic groups known to have a higher HCV prevalence), and several cost–effectiveness studies from the US and Portugal show that birth cohort testing is cost effective when compared to risk-based screening or current testing approaches (125, 166, 168, 190).
Routine testing in the general population. A major limitation of existing cost–effectiveness studies of testing in the general population is that they were conducted based on the use of interferon-based regimens and not using the new DAA curative treatments, and in HICs (125, 151, 160, 162, 163, 165, 167, 169, 170). Only one cost–effectiveness study has been undertaken in a LMIC – in Egypt, which has a very high prevalence of disease. Routine testing was shown to be cost-effective even when treatment was based on use of pegylated interferon (PEG-IFN) and ribavirin (PEG-RBV) (191).
Drivers of cost–effectiveness. In all analyses, the cost–effectiveness of testing for HCV was most sensitive to variations in prevalence, treatment efficacy (i.e. the replacement of IFN/RBV with significantly improved efficacy of DAAs), progression rates from chronic HCV to cirrhosis, and levels of linkage to care and treatment (164, 165, 170). It was relatively insensitive to costs of screening and treatment.
Based on this narrative review of heterogeneous studies of cost–effectiveness of testing approaches from HICs, the overall quality of evidence was rated as low.
6.6. Rationale for the recommendations on testing approaches for HCV infection
The Guidelines Development Group recognized that HCV epidemics around the world are heterogeneous but are largely represented by mixtures of three main epidemic patterns for which a specific testing approach is appropriate. These are as follows:
Infection related to high-risk behaviours – requiring focused or targeted testing in the highest-risk groups;
Infection related to past generalized exposures that have since been identified and removed (i.e. “birth cohort epidemic”) – requiring routine testing among specific birth cohorts that are readily identified and that have a high prevalence of HCV infection;
Generalized population epidemic with high prevalence generally related to a widespread, often iatrogenic, exposure – requiring routine testing throughout the entire population.
Few countries have epidemics that fall into one of the above three profiles. Rather, the majority have mixed epidemic profiles, with some combination of all these components. Determining the optimal strategic mix of HCV testing approaches to increase the diagnosis rate, and in particular, the approach to testing outside of high-risk risk groups will depend on a country's unique HCV epidemic profile (see
chapter 19).
The lack of evidence from LMICs on evaluation of different testing approaches was noted. Testing in high-risk behaviour groups and in settings with a large proportion of patients such as PWID, MSM, prisoners, HIV-infected persons and commercial sex workers was cost–effective in all settings. The best approach to testing outside of high-risk risk groups depends on a country's unique HCV epidemiology. Most countries have at least some component of a “birth cohort” epidemic, and “birth cohort” testing is likely to be cost–effective in most settings. In most epidemic settings, routine screening of the entire population may not be cost–effective.
Balance of benefits and harms
Focused risk-based testing. The Guidelines Development Group considered that those specific populations at the highest risk of acquisition and transmission of HCV such as PWID, people in prisons and other closed settings, MSM and sex workers should be prioritized for testing, as this was both cost–effective and had a high yield of case-finding. In settings with a high prevalence, this also means focused testing of adults and children with a clinical suspicion of chronic viral hepatitis infection (i.e. clinical symptoms or signs of cirrhosis or HCC, or abnormal liver function tests or ultrasound scan). Other higher-risk groups for focused testing include persons who have had tattoos, body piercing or scarification, unsafe medical procedures, received blood products in countries where screening of blood is not carried out routinely, as well as partners and close contacts of people with HCV infection. The Guidelines Development Group recognized that the priority groups will differ across countries and settings, and that it will be important to ensure adequate linkage to care after diagnosis.
Children. The Guidelines Development Group also considered that screening was indicated for children born to mothers with HCV infection (especially if also HIV infected) because of an increased risk for MTCT after 18 months of age.
Key benefits of focused testing
Focused testing in health facilities can successfully increase the uptake of viral hepatitis testing, case detection rate, and referral to specialist-level care and other key services.
Focused testing of these populations can be offered in high-prevalence settings such as harm reduction and drug treatment services for PWID. Other existing opportunities for health-facility -based testing can also be used (e.g. dedicated HIV, STI and TB outpatient clinics, and other primary care, outpatient and inpatient settings), as well as testing in the community.
A clinically guided testing approach is also likely to identify a larger proportion of people with HCV in highly endemic settings and therefore result in a lower cost per positive person found.
Risks of focused testing. Although ascertaining high-risk behaviours is a very effective way of identifying persons for testing, many people are unwilling to admit to stigmatizing behaviours, and health-care providers are also reluctant to ask (or have too limited time). As a result, medical records capture this information poorly, as the use of electronic medical records to flag high-risk persons for testing is limited.
Birth-cohort testing. The best approach to testing outside of groups with high risk behaviour or exposure depends on a country's unique HCV epidemiology. For example, in many settings, unsafe injection practices will probably have more of an impact on HCV prevalence than illicit injecting drug use. The Guidelines Development Group concluded that whenever there is an easily identified demographic group that has a high HCV prevalence (e.g. all individuals born in a certain time period), routine testing for HCV within that cohort, i.e. “birth cohort” testing will likely be cost–effective and should be considered. This will largely apply to those countries where routine screening of the blood supply for HCV in the 1990s and improvements in injection safety practices have since removed the exposure risk. A conditional recommendation was made mainly because of low quality of evidence.
Key benefits of birth cohort testing
Recent studies in the US showed birth cohort screening to be cost–effective when compared with risk-based screening. While typically identified as being the infection pattern in North America and Europe, many countries have at least some component of “birth cohort” epidemic in their HCV epidemiology, and therefore “birth cohort” testing is likely to be cost–effective in most settings.
A key advantage of this generally one-off screening approach is that it avoids the need to identify specific behavioural risks as the basis for screening, because providers may not be skilled at identifying high-risk behaviours, and individuals may not remember that they received a blood product, or report to previous risk-taking behaviour on direct questioning.
Key risks of birth cohort testing. More recent data suggest that a significant proportion of the HCV-infected population is not captured as part of birth cohort screening (192). A further challenge is that this approach requires reliable data on both the age distribution of the population and prevalence according to age, which is not available in most countries.
General population testing. Routine screening for HCV in the general population was generally not considered cost–effective outside specific settings with high general population prevalence. The application of a one-off birth cohort screening approach to testing the general population will be more widely applicable. Therefore, a conditional recommendation was made to support consideration of general population testing in intermediate- and high-prevalence settings.
Acceptability, values and preferences
A values and preferences survey of 104 stakeholders from 43 (20 high-income, 23 low- and middle-income) countries identified the following target populations as priority for hepatitis C testing: blood donors (>85%), children born to HCV-infected mothers (55%), persons living with HIV (50%), pregnant women (40%), MSM (25%), prisoners (25%), sex workers (<10%), and those chronically ill (25%). General population testing for HCV infection was supported by 30% of respondents.
