SOLUBLE CD8 AND SOLUBLE CD4 ANTIGENS IN VIRAL-HEPATITIS AND ALCOHOLIC CIRRHOSIS

Serum levels and production of soluble CD8 and soluble CD4 antigens by peripheral blood mononuclear cells were determined in patients with alcoholic cirrhosis and acute or chronic viral hepatitis. Patients with chronic viral hepatitis had significantly increased soluble CD8 serum levels (n=18; 734+/-143 U/ml) (mean+/-SD) compared to healthy controls (n=80; 312+/-141 U/ml; p<0.001) and patients with alcoholic cirrhosis (n=12; 505+/-256 U/ml; p=0.006), whose soluble CD8 concentrations were also higher than controls (p<0.001). In contrast, soluble CD4 antigen serum levels were similar in all groups. In addition, patients with chronic hepatitis showed an increased production of soluble CD8, but not soluble CD4, after mitogenic stimulation of their peripheral blood mononuclear cells compared to controls or patients with alcoholic cirrhosis. Patients with acute viral hepatitis, studied within the first 2 weeks after onset of jaundice, showed markedly elevated serum concentrations of soluble CD8 (n=4; 807+/-379 U/ml; p<0.001 vs. controls), but not soluble CD4. In addition, nine patients with chronic hepatitis C were studied during and after treatment with alpha interferon. Soluble CD8 serum concentrations of six treatment responders were not found to be different from the low levels seen in controls, whereas three non-responders had increased soluble CD8 levels which were similar to levels in untreated patients with chronic hepatitis C. After interferon-alpha therapy ended, a significant elevation of soluble CD8 serum concentrations was observed in four relapsing patients, which paralleled the serum ALT increase. In contrast, in two patients with sustained low ALT even after termination of interferon-alpha treatment, soluble CD8 serum concentrations remained in the normal range. Determination of soluble CD8 concentrations in serum could be a valuable parameter for the activation of cytotoxic T lymphocytes known to be involved in liver cell destruction in chronic liver disease. (C) Journal of Hepatology.