3RD-GENERATION HEPATITIS-C VIRUS TESTS IN ASYMPTOMATIC ANTI-HCV-POSITIVE BLOOD-DONORS

This study evaluated the performance of third-generation anti-HCV assays in blood donors who were positive by second-generation anti-HCV, and assessed any possible relationship between antibody patterns, HCV replication and liver damage. Fifty-two second-generation enzyme immunoassay-positive asymptomatic Italian blood donors were retested for anti-HCV by third-generation enzyme immunoassay and recombinant immunoblot assay (Ortho third-generation enzyme immunoassay, third-generation recombinant immunoblot assay), utilising recombinant C33c and NSS and synthetic peptide C100 and C22 antigens, and for HCV-RNA by ''nested'' polymerase chain reaction with 5' region primers. Alanine aminotransferases were tested monthly for 6 months. Two out of 52 second-generation enzyme immunoassay-positive donors were third-generation enzyme immunoassay, third-generation recombinant immunoblot assay and HCV-RNA negative. Among 50 third-generation enzyme immunoassay-positive cases, two had a third-generation enzyme immuno-assay optical density less than or equal to 1: one was third-generation recombinant immunoblot assay and HCV-RNA negative, and the other was third-generation recombinant immunoblot assay ''indeterminate'' and HCV-RNA-positive. The remaining 48 cases had third-generation enzyme immunoassay optical density>1: six were third-generation recombinant immunoblot assay negative (one HCV-RNA+ve), eight ''indeterminate'' (two HCV-RNA+ve) and 34 positive (22 HCV-RNA+ve), All ''indeterminate'' subjects reacted only to C22. HCV-RNA was positive in 22/34 cases with positive third-generation recombinant immunoblot assay (two or more Ags), 3/9 ''indeterminate'' and 1/11 negative. Alanine amino-transferases were abnormal in 13 cases with positive third-generation recombinant: immunoblot assay, one was ''indeterminate'' and three were negative. There was, however, a significant relation between C33c positivity and raised alanine aminotransferases (p<0.023). Reactivity to C33c was strongly related to viraemia; 21/29 C33c-positive cases were also HCV-RNA positive, as opposed to 5/25 C33c negative. Viraemia was often but not always associated with liver damage, alanine aminotransfoase levels being abnormal in 13/26 (50%) HCV-RNA positive and 4/28 (14%) HCV-RNA negative subjects (p<0.005). Third-generation HCV tests can reduce the number of second-generation enzyme immunoassay positive donors with a negative HCV-RNA. The concordance between third-generation enzyme immunoassay and third-generation recombinant immunoblot assay is high (96%). Some third-generation enzyme immunoassay/third-generation recombinant immunoblot assay positive, HCV-RNA-negative subjects might have latent viraemia. An ''indeterminate'' third-generation recombinant immunoblot assay pattern or even a negative third-generation recombinant immunoblot assay does not exclude active infection, since HCV-RNA is often present. (C) Journal of Hepatology.