Prognostic value of the soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alfa

Background/Aims: High serum levels of the soluble interleukin 2 receptor (sIL-2R) have been reported in patients with chronic hepatitis C. The aims of this study were to determine the evolution of sIL-2R considered as an indicator of activation of T cells in patients with hepatitis C virus (HCV) treated with IFN-α and to correlate sIL-2R serum levels with parameters reflecting ongoing liver disease and with outcome of interferon treatment. Methods: In a case-control study, we studied patients enrolled in a multicenter randomized clinical trial which had demonstrated the benefit of a reinforced regimen of interferon α. Each of the 26 sustained virological responders (SVR) was paired for treatment regimen with two non-responders (NR). Results: Prior to treatment, higher levels of sIL-2R were found in the sera of 78 patients compared with healthy controls (3791±210 pg/ml versus 956±88 pg/ml (p<0.001)). In the 78 patients after 4 weeks of treatment, the levels of sIL-2R were higher than pretreatment levels (4308±206 pg/ml (p<0.01)). In the NR, levels of sIL-2R increased significantly after 4 weeks of treatment compared with pretreatment levels (p<0.01), and levels of sIL-2R at week 72 were not significantly different from those at pretreatment. Conversely, in the SVR, levels of sIL-2R at week 4 did not significantly increase compared to pretreatment values, and thereafter gradually decreased. At week 72, levels of sIL-2R were significantly lower than before treatment (p<0.001). The difference between levels of sIL-2R at week 4 and before initiation of treatment (Δ s IL-2R) was smaller in the SVR than in the NR (142±219 pg/ml versus 704±107 pg/ml (p<0.02). The disappearance of HCV RNA from the serum at week 4 showed a sensitivity of 92% (95% confidence interval 86–98) and a specificity of 60% (95% confidence interval 49–71), Δ sIL-2R had a sensitivity of 42% (95% confidence interval 31–53) and a specificity of 81% (95% confidence interval 79–90) for the prediction of a sustained virological response 6 months after stopping treatment. The disappearance of HCV RNA from serum at week 4 and Δ sIL-2R were independent and early predictive factors for a sustained virological response 6 months after stopping treatment. Conclusions: At week 4, Δ sIL-2R may be a more specific parameter than the disappearance of HCV RNA for assessing total, and hence more sustained, elimination of HCV infection 6 months after stopping treatment.