RELATIONSHIP BETWEEN THE EFFECTOR T-CELL RESPONSE AND VIREMIA IN SYMPTOMATIC CHRONIC HEPATITIS-C

Objective.-The purpose of this study was to assess the relationship be tween hepatitis C virus (HCV) viremia, HCV genotype, histologic activi ty index, and intrahepatic densities of immunocompetent lymphoid cells in chronic hepatitis C.Method.-Liver biopsy specimens from patients w ith chronic hepatitis and anti-HCV antibodies, 5 with low-level HCV vi remia and 26 with high-level HCV viremia, were studied. Sections of sn ap-frozen specimens were immunostained with monoclonal antibodies dire cted against different subsets of B cells, follicular reticulum cells, and T cells, including CD45RA-naive cells and CD45RO-primed cells. Th e densities of each subset of lymphoid cells were calculated with a co mputerized image analyzer. Hepatitis C virus RNA was measured with a q uantitative branched DNA signal amplification assay, and HCV genotypes were determined with the line probe assay. Results.-A statistical cor relation was found between the level of HCV viremia and the histologic activity index (P = .002). There were also significant correlations b etween the densities of CD3(+) T cells and CD45RO'-primed cells in the liver and the histologic activity index and (P = .024 and P = .005, r espectively), and significant correlations were found between the dens ities of CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, and CD45RO(+) -primed cells and HCV viremia (P = .005, P = .03, P = .03, and P = .02 , respectively). Whatever the viremia status, CD45 RO-primed cells wer e more numerous than CD45RA-naive cells in lobules and portal tracts. The CD45RO/CD45RA ratio was significantly higher when intraportal lymp hoid aggregates were present. Eight patients were infected with genoty pe Ib, and 11 were infected with genotype 3b. There were no statistica l differences in the histologic activity index, viremia, and density o f immunocompetent cells in the liver between these two HCV genotypes. Conclusions.-The results of this study suggest that the density of ant igen-primed effector T cells in the liver of symptomatic patients with chronic hepatitis C is adapted to HCV viremia but is independent of t he occurrence of genotypes 1b or 3a, the most frequent genotypes found in France.