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 infecti on are poorly understood. To demonstrate which inflammatory cells migh t be responsible for the necroinflammatory damage in chronic hepatitis C infection, we have correlated the phenotype of the intrahepatic lym phocytes and macrophages with histological activity in liver biopsy an d explant specimens front 19 patients with chronic hepatitis C infecti on. In all stages of disease, more CD8(+) than CD4(+) lymphocytes were found. However, histologically active versus histologically mild hepa titis was associated with a trend toward greater parenchymal concentra tions of CD4(+) lymphocytes (0.71 +/- 0.27 per 10(4) mu m(2) versus 0. 35 +/- 0.15; not significant), significantly less parenchymal CD8(+) l ymphocytes (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 co ntaining cytotoxic granules between the two groups. Greater numbers of CD4(+) lymphocytes were found in liver biopsy specimens with little o r 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 dat a suggest that active histological disease in chronic hepatitis C infe ction may be associated with an increase in CD4(+) lymphocytes and sug gest that CD4(+) T cells may play an important role in the hepatic inj ury ill these patients.