BACKGROUND: In 1999, NAT of blood donations was implemented to detect “window-period” infections. Blood donors who have confirmed NAT results positive for the presence of HCV in the absence of anti-HCV are likely to have been recently infected. Of over 26.8 million donations tested between March 3, 1999, and March 31, 2003, 810 were HCV-reactive by NAT. A subset of these donors was assessed for recent exposure risk.

STUDY DESIGN AND METHODS: All anti-HCV– blood donors with reactive, unconfirmed HCV NAT results were invited to participate in a study that included an extensive demographic and risk questionnaire. Confirmed HCV+ cases were compared to HCV– (falsely positive) controls for histories of potential risk factors during the 6 months before donation.

RESULTS: Recent injection drug use (IDU) was independently associated with HCV infection (29.2% vs. 0% of cases vs. controls, p < 0.001). In addition, likely sources were identified for three other cases (4.6%), including occupational exposure, sexual contact with an HCV-infected partner (who was an IDU), and perinatal exposure, none of which was known to the donors at the time of donation. Incarceration was independently associated with HCV infection among the group not reporting IDU and after removal of the three donors with likely sources of risk (14.6% vs. 1.3% of cases vs. controls, p < 0.001).

CONCLUSIONS: A likely risk, primarily IDU, was found for 43 percent of HCV+ donors whose infections were identified solely by NAT. Because the maximum efficiency of the donor history questions may have been reached, NAT will continue to be an important measure to interdict recently infected blood donors.