title: Hepatic STAT1-nuclear translocation and interleukin 28B polymorphisms predict treatment outcomes in hepatitis C virus genotype 1-infected patients.
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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D044466:Asian People / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007564:Japan; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D021381:Protein Transport / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D050794:STAT1 Transcription Factor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494079:STAT1 protein, human; C100416:peginterferon alfa-2a