PATTERNS OF SEROLOGICAL MARKERS IN TRANSFUSION-TRANSMITTED HEPATITIS-C VIRUS-INFECTION USING 2ND-GENERATION HCV ASSAYS

A semiautomated dot blot assay and cDNA polymerase chain reaction (PCR) were used to study longitudinal anti-hepatitis C virus (HCV) recognition patterns in relation to presence of HCV-RNA in transfusion recipients and their infectious donors. In 9 recipients, 4 different patterns of HCV infection were observed: (A) persistent HCV carriage accompanied by chronic hepatitis in 6, (B) acute resolved hepatitis, but persistent HCV replication in one, and (C) continuous HCV replication without hepatitis in one and (D) acute resolved hepatitis with clearance of infection in one. This last self-limited infection was characterized by the disappearance of HCV-RNA as well as anti-HCV reactivity. In contrast, antibody reactivity persisted in 7 of 8 patients with chronic HCV infection who could be followed until 1990. Seven of the 9 recipients developed antibodies to all recombinant peptides in dot blot assay; one became positive for anti-C33 and anti-core and one developed anti-core only. The sequence of appearance of antibodies differed among individual patients. In 7 patients with full anti-HCV recognition patterns, the sequence of events was (mean and limits in days after transfusion): onset of hepatitis at day 50 (22-74), seroconversion of anti-C33 at day 91 (59-129), anti-core at day 133 (54-203), and anti-C100 at day 143 (59-365). The incorporation of C33 and core proteins, in addition to C100, in the second generation anti-HCV ELISA enhanced the detection rate in the HCV-infected transfusion recipients from 7/9 (78%) to 9/9 (100%). In 4 of the 7 anti-C100 seroconverters anti-HCV was detectable 38-277 days earlier in the new ELISA. However, the development of anti-HCV in the second-generation ELISA was still delayed [54-192 (mean 103) days after transfusion and 0-135 (mean 53) days after onset of hepatitis]. We conclude that combined application of anti-HCV immunoblot techniques and cDNA-PCR in consecutive samples is necessary for reliable,diagnosis of either ongoing productive or resolving HCV infection.