Analysis of the mononuclear inflammatory cell infiltrate in the cirrhotic, dysplastic nodules and hepatocellular carcinomas in patients with chronic hepatitis C infection

Abstract

Background: Hepatocarcinogenesis is a multistep process entailing the transitions from normal liver→ chronic hepatitis and cirrhotic nodules (CH/CNs) → dysplastic nodules (DNs) →hepatocellular carcinomas (HCCs). We hypothesized that hepatocarcinogeneis on top of chronic hepatitis C (CH-C) is associated with alterations in the mononuclear inflammatory cell infiltrate (MICs) in response to altered antigenicity of the damaged hepatocytes. Materials and Methods: A total of 19 hepatic resection specimens entailing the entire continuum of the lesional steps of the hepatocarcinogenesis (on top of CH-C) were evaluated for MICs using immunohistological methods and mouse monoclonal antibodies (CD3, CD20, CD68 and T-cell intracellular associated antigen, TIA-1). Results: HCCs were: 1) overrepresented in elderly males (56.1 ± 2.0 years, with male to female ratio of 1.8:1), and 2) more common in the right than in left lobe (1.1:1) The transitions from normal liver to the subsequent lesional steps (CH-C/CNs, DNs and HCCs) was associated with statistically significantly (p < 0.000) increased density of: tumor infiltrating lymphocytes (9.5 ± 0.2 vs. 87.1 ± 1.3 vs. 73.6 ± 1.6 vs. 72.1 ± 3.5), CD20+ B cells (4.4 ± 0.2 vs. 35.0 ± 2.9 vs. 11.3 ± 1.8 vs. 11.3 ± 1.6), CD68+ macrophages (1.4 ± 0.1 vs. 9.5 ± 1.8 vs. 22.3 ± 1.6 vs. 18.8 ± 2.0), CD3+ cells (5.4 ± 0.1 vs. 87.0 ± 1.3 vs. 62.2 ± 1.3 vs. 61.0 ± 3.4) and TIA-1+ cytototoxic T cells (0.4 ± 0.1 vs. 11.6 ± 2.0 vs. 24.9 ± 1.2 vs. 30.5 ± 1.6). Conclusions: Increased MICs during hepatocarcinogeneis (on top of CH-C) may reflect change in the antigenicity of the damaged hepatocytes. Although both B (humoral response) and T (cell mediated immunity) lymphocytes were involved, the later were the most numerous immunocytes. A considerable fraction of these T cells was TIA-1+ cells suggesting their cytotoxic potential. ©2005 Landes Bioscience.