BACKGROUND: T cell mediated immune destruction is an important mechanism of liver injury in patients with chronic hepatitis C. Serum levels of soluble interleukin-2 receptor(sIL-2R) seem to serve as a marker for the T cell activation and progressive liver injury, This study examined serum levels of sIft-2R and hepatitis C virus (HCV) RNA in patients with chronic HCV infection to determine the correlation with the severity of chronic hepatocellular damage. METHODS: Serum levels of sIft-2R in 73 patients with HCV infection (chronic hepatitis 52, liver cirrhosis 9, hepatocellular carcinoma 12) and 40 healthy controls were measured by sandwich enzyme immunoassay (CELLFREE, T Cell Sciences, USA). HCV RNA was quantified by QUANTIPLEX(TM) HCV RNA 2.0 assay (Chiron, USA) with duplication. This assay is a sandwich nucleic acid hybridization procedure using branched DNA amplification for the quantitation of HCV RNA. RESULTS: The sIL-2R levels of 52 patients with chronic hepatitis (591.4+/-238.7U/mL), 9 with liver cirrhosis(949.4+/-721.9 U/mL), and 12 with hepatocellular carcinoma (1,167.4+/- 554.4 U/mL) were significantly higher than those of healthy controls(370.8+/-71.8 U/mL) (p<0.001). A progressive and significant increase occurred in sIL-2R levels with chronic hepatitis C, liver cirrhosis and hepatocellular carcinoma (HCC) in order (p(0.001). The HCV RNA was detected in all patients and the means of HCV viral load were 3.3 MEq/mL in chronic hepatitis, 2.8 MEq/mL in cirrhosis, and 3.7 MEq/mL in HCC. There was no significant correlation between HCV RNA and the severity of liver injury in chronic HCV infection. There were no correlations among sIL-2R, HCV RNA and serum ALT. CONCLUSIONS: These results suggest that chronic hepatocellular injury by HCV progress mainly by T cell mediated immune response, not by direct cytopathic injury. Also, sIL-2R can be useful as a marker in monitoring the patients with HCV infection at high risk of getting HCC.