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Predictive value of suppressor of cytokine signal 3 (SOCS3) in the outcome of interferon therapy in chronic hepatitis C


Dr Hisamitsu Miyaaki, The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Email:


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.

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