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 between hepatitis C virus (HCV) viremia, HCV genotype, histologic activity index, and intrahepatic densities of immunocompetent lymphoid cells in Chronic hepatitis C. Method. - Liver biopsy specimens from patients with chronic hepatitis and anti-HCV antibodies, 5 with low-level HCV viremia and 26 with high-level HCV viremia, were studied. Sections of snap-frozen specimens were immunostained with monoclonal antibodies directed against different subsets of B cells, follicular reticulum cells, and T cells, including CD45RA-naive cells and CD45RO-primed cells. The densities of each subset of lymphoid cells were calculated with a computerized image analyzer. Hepatitis C virus RNA was measured with a quantitative branched DNA signal amplification assay, and HCV genotypes were determined with the line probe assay. Results. - A statistical correlation was found between the level of HCV viremia and the histologic activity index (P = .002). There were also significant correlations between the densities of CD3⁺ T cells and CD45RO⁺- primed cells in the liver and the histologic activity index and (P = .024 and P = .005, respectively), and significant correlations were found between the densities 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, CD45RO-printed cells were more numerous than CD45RA-naive cells in lobules and portal tracts. The CD45RO/CD45RA ratio was significantly higher when intraportal lymphoid aggregates were present. Eight patients were infected with genotype 1b, and 11 were infected with genotype 3b. There were no statistical differences in the histologic activity index, viremia, and density of immunocompetent cells in the liver between these two HCV genotypes. Conclusions. - The results of this study suggest that the density of antigen-primed effector T cells in the liver of symptomatic patients with chronic hepatitis C is adapted to HCV viremia but is independent of the occurrence of genotypes 1b or 3a, the most frequent genotypes found in France.