Predictive value of the phosphorylation of signal transducers and activators of transcription in the outcome of interferon therapy for chronic hepatitis C

Intervirology. 2008;51(6):394-9. doi: 10.1159/000205264. Epub 2009 Mar 4.

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.

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferons / pharmacology
  • Interferons / therapeutic use*
  • Liver / cytology
  • Liver / drug effects*
  • Liver / immunology
  • Liver / metabolism
  • Male
  • Middle Aged
  • Phosphorylation
  • STAT1 Transcription Factor / biosynthesis
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • STAT3 Transcription Factor / biosynthesis
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • Interferons