Prognostic value of the soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alfa. Multicenter GER-CYT 04 Group.
OBJECTIVE
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-alpha 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 alpha. 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 (delta 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), delta 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 delta sIL-2R were independent and early predictive factors for a sustained virological response 6 months after stopping treatment.


CONCLUSIONS
At week 4, delta 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.
Naveau
S
S
Service d'Hépatogastroentérologie, Hôpital Antoine Béclère, Clamart, France.
Balian
A
A
Degos
F
F
Daurat
V
V
Chevret
S
S
Gayno
S
S
Bastie
A
A
Riachi
G
G
Bartolomei-Portal
I
I
Barange
K
K
Moussalli
J
J
Bailly
F
F
Chaumet-Riffaud
P
P
Emilie
D
D
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012016:Reference Values; D012995:Solubility; D016896:Treatment Outcome
D016898:Interferon-alpha; D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D000410:Alanine Transaminase