Intrahepatic lymphocyte phenotypes in hepatitis C virus infection: a comparison between cirrhotic and non-cirrhotic livers.

Aim: The pathogenesis of viral hepatitis involves the activation of cellular immunity, including intrahepatic lymphocytes (IHL). Lym-phocyte phenotypes play a fundamental role in the pathogenesis of chronic hepatitis C virus (HCV) infection, the progression of liver fibrosis and subsequent hepatocellular carcinoma. The aim of this study was to evaluate the frequency of intrahepatic mononuclear cell phenotypes in patients with chronic HCV. Another aim was to assess the relationship of nonparenchymal cells with liver fibrosis.

Methods: Liver fibrosis was evaluated with the Histologic Activity Index. Fourteen liver biopsies showed mild fibrosis (group 1), and 11 bridging fibrosis (group 2). Fourteen samples were explants from HCV patients who underwent liver transplantation (group 3). CD4 and CD8 T-lymphocytes, CD20 (B lymphocytes), CD16 (macrophage), and CD57 (NK) cells were detected using monoclonal antibodies on paraffin-embedded tissue.

Results: A minority of lobular cells stained for T- or B-lymphocytes. Most lobular cells stained with macrophage antibodies, and were more common in bridging fibrosis, compared to mild fibrosis. The percentages of lobular CD4 and CD8 cells were significantly lower in regenerative nodules of cirrhotic livers. There was a strong negative correlation between lobular CD8 and fibrosis score (R= -0.65), and a strong positive correlation between CD16-stained mononuclear cells (macrophages) and fibrosis score (R=0.66). In portal and periportal areas, CD4 but not CD8 lymphocytes decreased in parallel with fibrosis. B-lymphocytes were more commonly found in the portal areas than in the lobule. CD57-positive cells were rare in both lobule and portal areas, and their frequency was not different in the three groups studied.

Conclusions: In hepatitis C, lobular mononuclear cells are mostly macrophages and appear associated with bridging fibrosis. Cirrhotic livers display significantly lower numbers of lobular CD4 and CD8 lymphocytes. This finding could help explain a decrease in immune surveillance and the promotion of neoplastic growth in HCV-associated cirrhosis.