Low-positive anti-hepatitis C virus enzyme immunoassay results: An important predictor of low likelihood of hepatitis C infection

Background: Tests for hepatitis C antibodies (anti-HCV enzyme immunoassays) are usually described as positive or negative. Several studies, mainly in blood donors, have found that specimens with low signal/cutoff NO ratios are commonly negative when tested with a recombinant immunoblot assay (RIBA) or for HCV RNA. Methods: We retrospectively reviewed 17 418 consecutive anti-HCV results from a screening program for high-risk veterans; 2986 (17.1%) samples were anti-HCV-positive, and 490 (16.4%) had S/C ratios less than or equal to3.7 (low positive). Additional tests were performed in 1814 anti-HCV-positive individuals. Results: RIBA was performed in 263 patients with low-positive anti-HCV; results were negative in 86%, indeterminate in 12%, and positive in 2%. Only 16 of 140 individuals (11%) with low-positive anti-HCV values were HCV RNA-positive, whereas HCV RNA was positive in 90% of 1435 individuals with high-positive anti-HCV values (P < 0.0001). Compared with those with high-positive anti-HCV, individuals with low-positive anti-HCV values were older (P < 0.0001) and were less likely to have risk factors for HCV (P < 0.0001 for most), multiple increased alanine aminotransferase (ALT) activity values (30% vs 81%; P < 0.0001), or positive antihepatitis B core antigen (19% vs 59%; P < 0.0002). Among 634 individuals with high anti-HCV titers and multiple increased ALT activity values, 95% were HCV RNA positive. Conclusions: The S/C ratio is important even in high-risk individuals; laboratories should report the S/C ratio along with anti-HCV EIA results and perform supplemental RIBA testing in those with low-positive values to avoid reporting false-positive results. (C) 2003 American Association for Clinical Chemistry.