Hepatic STAT1-nuclear translocation and interleukin 28B polymorphisms predict treatment outcomes in hepatitis C virus genotype 1-infected patients

PLoS One. 2011;6(12):e28617. doi: 10.1371/journal.pone.0028617. Epub 2011 Dec 12.

Abstract

Background: We investigated associations between signal transducer and activator of transcription (STAT) 1 in pretreated liver tissues, interleukin (IL) 28B polymorphism and treatment response in hepatitis C virus (HCV)-infected patients treated with peginterferon and ribavirin.

Methods and findings: We performed immunostaining analysis of STAT1 in liver tissues and determined IL28B polymorphism at rs8099917. We then compared the results with treatment outcomes in HCV genotype 1 patients with high viral load who were receiving peginterferon plus ribavirin. In univariate analysis, younger age, white blood cell counts, virological responder, early virological responder (EVR), mild activity (A1) of liver inflammation grading, and lower STAT1 nuclear-stain of hepatocytes in zone 1, zone 2 and total zones of liver were associated with sustained virological responder (SVR). Multivariate analysis showed that EVR, age and hepatic STAT1 nuclear-stain in zone 2 of liver were independent predictors of SVR. It was also revealed that IL28B and STAT1-nuclear translocation in hepatocytes are independent predictors of response to treatment with peginterferon and ribavirin in chronic hepatitis C patients.

Conclusions: Concomitant assessment of lower STAT1 nuclear-stain of hepatocytes and IL28B polymorphism is useful for prediction of SVR in HCV genotype 1 patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Hepatocytes / virology
  • Humans
  • Immunohistochemistry
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Japan
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Liver / virology
  • Male
  • Middle Aged
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide / genetics*
  • Protein Transport / drug effects
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use
  • STAT1 Transcription Factor / metabolism*
  • Treatment Outcome

Substances

  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a