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


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.
Hussein
Mahmoud R
MR
Department of Pathology, Assiut University Hospitals, Faculty of Medicine, Assiut, Egypt. mrh17@swissinfo.org
Ahmed
Rabab A
RA
D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000601:surgery; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology