SIGNIFICANCE OF HIGHLY POSITIVE C22-3 INDETERMINATE 2ND-GENERATION HEPATITIS-C VIRUS (HCV) RECOMBINANT IMMUNOBLOT ASSAY (RIBA) AND RESOLUTION BY 3RD-GENERATION HCV RIBA

Second-generation recombinant immunoblot assay (RIBA) is widely used f or the validation of anti-hepatitis C virus (HCV) antibody detection. The aims of this work were (i) to determine, in terms of liver disease and HCV replication, the significance of a peculiar ''indeterminate'' second-generation RIBA pattern characterized by the presence of high titers of antibodies directed to c22-3, a protein bearing core epitope s and (ii) to determine whether a more advanced version of the same st rip assay, namely a third-generation RIBA, mag solve the problem of su ch indeterminate patterns. Sixty patients for which c22-3 indeterminat e second-generation RIBAs were highly positive were studied. Forty-two of them (70%) were immunocompromised. Serum transaminases were increa sed in 46 cases (77%), and HCV RNA was detected by PCR in 50 cases (83 %). Third-generation RIBA remained highly positive c22 indeterminate f or 9 patients (15%) but was positive for 51 (85%), mostly because of i ncreased sensitivity for the detection of both anti-c100 and anti-c33c antibodies. These results suggest that third-generation RIBA mag achi eve resolution of most of these cases but that highly positive c22 ind eterminate third-generation RIBA mag persist when used with some patie nts with very low titers of anti-HCV nonstructural protein antibodies.