Predictive value of the phosphorylation of signal transducers and activators of transcription in the outcome of interferon therapy for chronic hepatitis C.
OBJECTIVE
Signal transducers and activators of transcription (STATs) play a critical role in antiviral defense. To better understand pegylated interferon (IFN)-alpha and ribavirin combination therapy resistance, we examined the STAT expression in the liver.


METHODS
We immunostained Phospho-STAT1 (P-STAT1) and Phospho-STAT3 (P-STAT3) in 59 hepatitis C virus (HCV)-infected liver tissues and compared the expression of these STATs proteins and the clinicopathological factors.


RESULTS
The number of P-STAT1 observed correlated significantly with the body mass index (BMI; p = 0.03) and homeostatic model assessment (p = 0.007). The number of P-STAT3 observed correlated significantly with the ALT level (p = 0.002) and platelet count (p = 0.002). The number of P-STAT1 nuclei in the sustained virological response (SVR) group was significantly larger than in the non-SVR group (p = 0.003). On multivariance analysis, the number of P-STAT1 nuclei (p = 0.004) and age (p = 0.016) were significant predictors of SVR.


CONCLUSIONS
P-STAT1 in the liver tissue prior to IFN therapy correlated with an increased BMI and increased insulin resistance, and might be a useful predictor of HCV clearance by IFN therapy. On the other hand, P-STAT3 might play a critical role in the hepatocellular response against inflammatory damage.
Miyaaki
Hisamitsu
H
First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. miyaaki-hi@umin.ac.jp
Ichikawa
Tatsuki
T
Nakao
Kazuhiko
K
Takeshita
Shigeyuki
S
Shibata
Hidetaka
H
Ozawa
Eisuke
E
Akiyama
Motohisa
M
Miuma
Satoshi
S
Eguchi
Katsumi
K
D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016896:Treatment Outcome
D000998:Antiviral Agents; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D007372:Interferons