Predictive value of suppressor of cytokine signal 3 (SOCS3) in the outcome of interferon therapy in chronic hepatitis C
Article first published online: 13 JUL 2009
© 2009 The Japan Society of Hepatology
Volume 39, Issue 9, pages 850–855, September 2009
How to Cite
Miyaaki, H., Ichikawa, T., Nakao, K., Matsuzaki, T., Muraoka, T., Honda, T., Takeshita, S., Shibata, H., Ozawa, E., Akiyama, M., Miuma, S. and Eguchi, K. (2009), Predictive value of suppressor of cytokine signal 3 (SOCS3) in the outcome of interferon therapy in chronic hepatitis C. Hepatology Research, 39: 850–855. doi: 10.1111/j.1872-034X.2009.00529.x
- Issue published online: 27 AUG 2009
- Article first published online: 13 JUL 2009
- Received 7 January 2009; revision 3 March 2009; accepted 12 March 2009.
- hepatic C virus;
- insulin resistance;
- signal transducers and activators of transcription;
- suppressor of cytokine signaling 3
Aims: Suppressor of cytokine signaling 3 (SOCS3) can suppress Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling by blocking an IFN-induced protein. In this study, the relationship between SOCS3 and phosphorylation of STAT1 in the liver and outcome of interferon therapy were examined.
Methods: Prior to interferon treatment, we immunostained for SOCS3 and phosphorylated-STAT1 (P-STAT1) in 59 liver specimens from chronic hepatitis C virus (CHC) patients and compared the expression of SOCS3 and clinicopathological factors. Fifty-one patients were receiving peg-interferon alpha-2b and ribavirin therapy and also compared interferon therapy effect and the expression of SOCS3.
Results: Immunostaining for SOCS3 was mainly seen in the periportal area. The concentration of P-STAT1 nuclei was significantly larger in specimens with < 30% area immunostaining to SOCS3 than those in which this area was ≥ 30% (10.6 ± 8.8 vs. 4.6 ± 6.1, P = 0.004). SOCS3 immunostaining score was significantly correlated with aspartate amino transferase (r = 0.373, P = 0.003), alanine amino transferase (r = 0.337, P = 0.008), platelets (r = −0.273, P = 0.037), and homeostatic model assessment (r = 0.339, P = 0.008). On univariate analysis and multivariate analysis, SOCS3 immunostaining score (0 or 1) and age (<60 years old) were significant predictors of interferon response (odds ratio 10.888; P = 0.010; odds ratio 3.817, P = 0.045 respectively).
Conclusion: SOCS3 expression in the liver prior to interferon therapy was correlated with increased insulin resistance and might be a useful predictor of HCV clearance by interferon therapy.