These authors contributed equally to this study.
Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus–related chronic hepatitis: Insulin resistance and response to antiviral therapy†
Article first published online: 1 AUG 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 4, pages 1009–1015, October 2007
How to Cite
Persico, M., Capasso, M., Persico, E., Svelto, M., Russo, R., Spano, D., Crocè, L., La Mura, V., Moschella, F., Masutti, F., Torella, R., Tiribelli, C. and Iolascon, A. (2007), Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus–related chronic hepatitis: Insulin resistance and response to antiviral therapy. Hepatology, 46: 1009–1015. doi: 10.1002/hep.21782
Potential conflict of interest: Nothing to report.
- Issue published online: 25 SEP 2007
- Article first published online: 1 AUG 2007
- Manuscript Accepted: 18 APR 2007
- Manuscript Received: 7 FEB 2007
- Funds for Projects of Relevant National Interest (2005-2007) from the Italian Ministry of University
- Italian Ministry of Scientific and Biotechnological Research
The response to antiviral therapy is lower in hepatitis C virus (HCV) patients with genotype 1 than in those with genotype 2. Overexpression of the suppressor of cytokine signaling 3 (SOCS3) gene in liver tissue is associated with a poorer treatment outcome in patients with chronic hepatitis C viral genotype 1. Also, insulin resistance has been implicated in nonresponse to an anti-HCV treatment. To understand why HCV genotype 1 patients respond differently, we investigated SOCS3 gene expression, metabolic syndrome (MS), and the response to therapy in a cohort of patients with HCV-related hepatitis. A total of 198 patients (108 with genotype 1 and 90 with genotype 2) treated with pegylated interferon plus ribavirin were consecutively enrolled in the study. We measured SOCS3 expression in Epstein-Barr virus–transformed lymphoblastoid cell lines derived from peripheral lymphocytes of a subset of 130 patients. MS was more frequent in genotype 1 patients than in genotype 2 patients (P < 0.01). Nonresponders (P < 0.01), MS (P < 0.001), and genotype 1 (P < 0.001) were significantly related to SOCS3 overexpression. However, SOCS3 levels were higher in nonresponders also, regardless of the genotype (P < 0.01). In a univariate analysis, the genotype (P < 0.001), age (P < 0.001), SOCS3 (P < 0.001), and MS (P < 0.001) were significantly related to the response to therapy. However, in a multivariate analysis, SOCS3 was the only independent predictor of the response (odds ratio = 6.7; P < 0.005). Conclusion: We speculate that SOCS3 expression per se may influence the response to antiviral therapy and that the genotype 1b virus might induce its up-regulation. This may account for the different responses to therapy between genotype 1–infected and genotype 2–infected patients. (HEPATOLOGY 2007.)