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Differential reactivity of anti-hepatitis C virus screening assays in patients with waning antibodies

Hepatitis C virus (HCV) leads to persistent infection. Viral clearance can be obtained through pharmacological treatment or spontaneously. After viral clearance, anti-HCV antibodies (Abs) slowly decline and finally disappear. Subjects with a resolved HCV infection are reactive to anti-HCV screening assays for a long time. These subjects pose a diagnostic challenge, and therefore, a more accurate interpretation of laboratory tests is needed for cases with resolved HCV infection. However, the performances of anti-HCV screening assays against declining anti-HCV Abs have not been assessed. Here we evaluated 1509 samples with different screening assays. Screening assays provided discrepant results in patients with waning Abs. The identification of signal-to-cut-off values indicative of waning Abs for each anti-HCV assay could avoid unnecessary confirmatory tests and reduce the impact of misdiagnosis.