Association among Fas expression in leucocytes, serum Fas and Fas-ligand concentrations and hepatic inflammation and fibrosis in chronic hepatitis C.
BACKGROUND
Replication of the hepatitis C virus (HCV) in peripheral blood mononuclear cells (PBMC) may impair immune functions and establish persistent infection. The aim of this study was to assess the influence of HCV on PBMC and their susceptibility to apoptosis in relation to liver inflammation and fibrosis.


METHODS
Eighty-one patients with chronic hepatitis C (CHC) were enrolled in this study. Flow cytometry was used to determine the amount of T cells (CD4(+), CD8(+)), B cells (CD19(+)), monocytes (CD14(+)) and natural killer cells (CD16(+)) in the peripheral blood and the expression of CD95(+) (CD95/APO-1) in each subset. Serum concentrations of sFas and sFasL were assessed by the enzyme-linked immunosorbent assay method.


RESULTS
An increased expression of Fas was observed in CD4(+) and CD8(+) cells in CHC. There was a more prominent expression of Fas on CD4(+) cells in HCV genotype 1b in contrast to 3a. Increased Fas expression on CD4(+) cells was seen in advanced stages of liver disease. Fas expression on monocytes was lower in advanced stages of liver inflammation and fibrosis. Serum sFas concentration was higher in CHC compared with the control group. There was an association between sFasL concentration and inflammatory activity in the liver. Serum sFasL concentration correlated positively with the mean intensity of fluorescence of the Fas receptor in CD4(+) and CD8(+) cells, granulocytes and monocytes.


CONCLUSIONS
These findings indicate that there is an increased susceptibility of PBMC to apoptosis, which can be attributed to the constant contact of leucocytes with the inflamed liver tissue, or from direct HCV influence.
Panasiuk
Anatol
A
Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
Parfieniuk
Anna
A
Zak
Janusz
J
Flisiak
Robert
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D053222:Fas Ligand Protein / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D019014:fas Receptor / Q000097:blood*
D053222:Fas Ligand Protein; D019014:fas Receptor