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


CONCLUSIONS
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.
Miyaaki
Hisamitsu
H
The First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Japan.
Ichikawa
Tatsuki
T
Nakao
Kazuhiko
K
Matsuzaki
Toshihisa
T
Muraoka
Toru
T
Honda
Takuya
T
Takeshita
Shigeyuki
S
Shibata
Hidetaka
H
Ozawa
Eisuke
E
Akiyama
Motohisa
M
Miuma
Satoshi
S
Eguchi
Katsumi
K