title: Predictive value of the phosphorylation of signal transducers and activators of transcription in the outcome of interferon therapy for chronic hepatitis C.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. miyaaki-hi@umin.ac.jp
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Miyaaki
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakao
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Takeshita
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Shibata
authors.forename: Eisuke
authors.initials: E
authors.lastname: Ozawa
authors.forename: Motohisa
authors.initials: M
authors.lastname: Akiyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miuma
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D007372:Interferons