Lymphocyte and macrophage phenotypes in chronic hepatitis C infection. Correlation with disease activity.
The pathogenesis of chronic hepatitis C and the mechanisms underlying progressive liver disease in patients with chronic hepatitis C infection are poorly understood. To demonstrate which inflammatory cells might be responsible for the necroinflammatory damage in chronic hepatitis C infection, we have correlated the phenotype of the intrahepatic lymphocytes and macrophages with histological activity in liver biopsy and explant specimens from 19 patients with chronic hepatitis C infection. In all stages of disease, more CD8+ than CD4+ lymphocytes were found. However, histologically active versus histologically mild hepatitis was associated with a trend toward greater parenchymal concentrations of CD4+ lymphocytes (0.71 +/- 0.27 per 10(4) microns 2 versus 0.35 +/- 0.15; not significant), significantly less parenchymal CD8+ lymphocytes (0.90 +/- 0.1 versus 1.70 +/- 0.3; t = 2.32, P = 0.03) and a greater parenchymal CD4/CD8 ratio (4.1 +/- 2.8 versus 0.91 +/- 0.3; t = 1.65, P = 0.07). No difference was found in the number of cells containing cytotoxic granules between the two groups. Greater numbers of CD4+ lymphocytes were found in liver biopsy specimens with little or no staining for hepatitis C virus antigen (1.47 +/- 0.88 versus 0.27 +/- 0.27; t = 2.28, P < 0.05). No significant differences were found in the macrophage subsets between the three stages of disease. Our data suggest that active histological disease in chronic hepatitis C infection may be associated with an increase in CD4+ lymphocytes and suggest that CD4+ T cells may play an important role in the hepatic injury in these patients.
Khakoo
S I
SI
Academic Department of Medicine, Royal Free Hospital, London, United Kingdom.
Soni
P N
PN
Savage
K
K
Brown
D
D
Dhillon
A P
AP
Poulter
L W
LW
Dusheiko
G M
GM
D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002452:Cell Count; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D008099:Liver / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008856:Microscopy, Fluorescence