Prospective study of the meaning of indeterminate results of the recombinant immunoblot assay for hepatitis C virus in blood donors.

Abstract The interpretation of "indeterminate" results of the recombinant immunoblot assay (RIBA) is a particularly sensitive issue for Transfusion Services, and donors with such a serological condition require long-term follow-up. In the Immunohaematology and Transfusion Medicine Division of Umberto I University Hospital (Rome, Italy), 102,979 donor blood units were screened for hepatitis C virus (HCV) antibodies by enzyme-linked immunosorbent assay (ELISA) over a 5-year period (01.01.2000 - 31.12.2004). Since 24.10.2001, HCV-RNA testing was added. All samples repeatedly reactive by ELISA were then submitted to a HCV confirmatory assay (RIBA). Among the 102,979 donors we found 271 positive to HCV ELISA testing. The results of the RIBA assay for these donors were negative in 178 (65.7%) cases, positive in 28 (10.3%) and indeterminate in 65 (24.0%). Of the 65 subjects with an indeterminate pattern, 24 completed a sufficient follow-up (median 25 months; range, 6 - 52), during which some (n = 8; 33%) converted to a negative status, some (n = 16; 67%) maintained their reactivity pattern, but none became seropositive for HCV. The HCV-RIBA indeterminate status may indicate either a non-specific reaction (false positive) or a real pre-existing or initial infection and does not, therefore, enable a prediction of outcome. The use of HCV genomic assays (nucleic acid amplification testing), which are more specific than antibody-based assays (ELISA, RIBA), therefore improves HCV blood donor testing by allowing an accurate interpretation of such primary assays.