Objectives: Hepatitis C virus (HCV) infection induces extra-hepatic manifestations, most of which are considered to be mediated by circulating immune complexes. For evaluating this association in a wider perspective, complement activity was determined in sera from apparently healthy individuals, and hypocomplementemia was tested for correlation with HCV viremia.
Methods: Sera from 10,532 voluntary blood donors were stored at 4 degrees C overnight, serially diluted 2-fold, and tested for hemolytic activity by a microtitration method and antibody to HCV (anti-HCV) by passive hemagglutination with recombinant HCV antigens of the second generation. HCV RNA was determined in sera with anti-HCV or hypocomplementemia, or both, by polymerase chain reaction with nested primers deduced from the 5'-noncoding region of the HCV genome.
Results: Hypocomplementemia was detected in 53 (0.5%) of 10,532 donations and anti-HCV in 94 (0.9%). Anti-HCV was detected in 48 (91%) of the 53 sera with hypocomplementemia, more frequently than in 46 (0.44%) of 10,479 sera without (p < 0.001). Among 94 sera positive for anti-HCV, HCV RNA was detected in 45 (94%) of 48 sera with hypocomplementemia, more often than in 10 (22%) of 46 sera without (p < 0.001).
Conclusions: A close association of hypocomplementemia with HCV viremia among apparently healthy blood donors would reflect circulating immune complexes which may cause extrahepatic diseases, such as cryoglobulinemia and membranoproliferative glomerulonephritis, in some HCV carriers. The storage of sera from HCV carriers at 4 degrees C before the test would have contributed to a decreased hemolytic activity due to the cold activation of complement by cryoglobulins involving HCV.