Inflammatory markers in chronic hepatitis C.
To test the hypothesis that inflammation in hepatitis C follows mechanisms common to immune-activated pathways, the distributions of T and B cells, adhesion molecules and transforming growth factor-beta (TGF-beta) were assessed in liver biopsies with chronic inflammation due to hepatitis C (HCV, n = 8) and other causes (non-HCV, n = 10). Frozen sections were immunostained using primary antibodies to CD2, CD20, CD4, CD8, intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM)-1, HLA-DR, lymphocyte function-associated antigen (LFA)-1, and TGF-beta. Inflammatory cells positive for each immunophenotypic marker were counted, and positive staining for adhesion molecules, HLA-DR and TGF beta was graded in triads and lobules and compared in HCV and non-HCV biopsies. In all biopsies, T cells were more frequent than B cells, both in triads and lobules. CD20+, CD4+, CD8+ and LFA-1+ cells were increased in HCV compared to non-HCV biopsies. Portal lymphoid aggregates were present in 6 of 8 HCV biopsies and 3 of 10 non-HCV biopsies. Aggregates consisted of CD20+, CD4+, CD8+ and LFA-1+ cells, and ICAM-1 and VCAM-1 were increased. Sinusoidal lining cells in HCV biopsies and non-HCV biopsies with inflammation expressed HLA-DR, ICAM-1, and CD4. TGF-beta was increased in foci of necrosis. Inflammation in chronic HCV involves common immune-mediated cellular effector pathways and the inflammation in the portal triads represents aggregation of both T and B cells, mediated in part by upregulation of adhesion molecules on portal stromal cells; this is possibly in response to antigens draining from necroinflammatory foci in the lobules. TGF-beta is increased in active necroinflammatory foci, but not in portal lymphoid aggregates.
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Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA.
Allan
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C
Savas
L
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Baker
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S
Barnard
G
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Bonkovsky
H L
HL
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D001706:Biopsy; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D015703:Antigens, CD; D015415:Biomarkers; D016169:Lymphocyte Function-Associated Antigen-1; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1