of confirming a positive EIA: to make sure that the antibodies detected in the EIA were truly to HCV and not cross-reactive and to assess persons with antibodies to HCV to ascertain whether HCV infection is current or cleared spontaneously. The likelihood that a positive HCV EIA represents antibodies to HCV (as opposed to cross-reactive antibodies) depends on the strength of the EIA reaction. Values that exceed a particular threshold (for example, 3.8 for tests commonly used in the United States) are likely to be true HCV infections and unlikely to be false-positive (Alter et al., 2003; Pawlotsky et al., 1998). Thus, some laboratories report the ratio of the test result to the cutoff value, and ratios above that threshold can be assumed to represent HCV antibodies. Another way to establish whether a positive EIA reflects HCV antibodies is to run a supplemental antibody test, such as a RIBA recombinant immunoblot assay. By separating the antigens that are grouped in the screening EIA, the supplemental antibody test provides better specificity (Damen et al., 1995). However, supplemental antibody testing does not achieve the second goal of determining whether a person has HCV infection. Thus, most authorities recommend use of HCV-RNA testing as the next step after detection of HCV antibodies with EIA in all settings in which HCV testing is done in at-risk persons (Alter et al., 2003; Ghany et al., 2009). A positive result in both EIA and RNA tests means that a person needs further counseling and medical evaluation for chronic or acute HCV infection.

HCV-RNA testing is more expensive than antibody testing with EIA and may require more sophisticated laboratory capability and a longer reporting interval (Alter et al., 2003). Thus, although all reasonable efforts should be made to confirm positive EIA HCV results before presenting them, HCV-RNA testing may not be feasible in some settings. Lack of available HCV-RNA testing should not be an impediment to EIA testing, but counseling must reflect the uncertainty and the urgency of followup in another venue for further assessment.

Laboratory testing of at-risk populations to identify HCV-infected people has been found to be cost-effective when combined with proper medical-management and harm-reduction strategies (Tramarin et al., 2008). In particular, studies have found that HCV laboratory testing among current and former IDUs is cost-effective. A 2006 study of former IDUs in a prison in the United Kingdom found that laboratory testing and later treatment of inmates cost £16,514 (about $25,000) per quality adjusted life year (Castelnuovo et al., 2006). A 2008 study in Italy found that laboratory testing (followed by appropriate medical management) of IDUs resulted in a substantial difference in the incidence of premature death. In contrast, HCV laboratory testing for people who are in the hospital for surgery but have no other risk factors is unlikely to be cost-effective (Tramarin et al., 2008).

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