Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-α

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Abstract
To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1β, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P=0.0026), β2-microglobulin (P=0.046), soluble interleukin-2 receptor (P=0.021), and soluble CD8 (PP=0.023). Significant correlations were observed between β2-microglobulin concentration and Knodell's index (r=0.638,P=0.00045), the score of piecemeal necrosis (r=0.572,P=0.0023), and the degree of fibrosis (r=0.527,P=0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r=0.412,P=0.037), and the degree of lobular cytolysis (r=0.389,P=0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P=0.042) in patients with a sustained biochemical response. On interferon-α treatment, the levels of β2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P<0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-γ.