title: Peripheral Blood Mononuclear Cell Gene Expression Remains Broadly Altered Years after Successful Interferon-Based Hepatitis C Virus Treatment.
abstract: BACKGROUND
  Inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) is altered in chronic Hepatitis C Virus (HCV) infection. Duration of changes after pegylated interferon- (peg-IFN-) based HCV treatment is unclear.
  
  
  METHODS
  PBMC mRNA expression of 184 inflammatory response genes was analyzed (nCounter GX Human Inflammation Kit, Nanostring) from peg-IFN treatment nonresponders (NR, n = 18), sustained virologic responders (SVR, n = 22), and spontaneous clearers (SC, n = 15). Logistic regression was used for comparison.
  
  
  RESULTS
  Median time from last treatment was 2 and 2.7 years in SVR and NR, respectively (p = NS). Mean mRNA counts were significantly different for 42 and 29 genes comparing SVR to SC patients and NR to SC, respectively, and no genes comparing SVR to NR. Differential expression of 24 genes was significantly different in both SVR and NR groups compared to SC. Among these 24 acute and chronic inflammatory cascade genes, significant upregulation was noted for proinflammatory transcription regulators Fos, CEBPB, and MyD88 in SVR and NR compared to SC. HDAC4 was significantly downregulated in SVR and NR compared to the SC group.
  
  
  CONCLUSIONS
  PBMC inflammatory gene expression patterns in SVR resemble NR more than SC patients. A generalized inflammatory response persists in PBMCs long after successful peg-IFN treatment for HCV infection.
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94304, USA ; Division of Infectious Diseases & Geographic Medicine, Stanford University, Stanford, CA 94305-5107, USA.
authors.forename: Paul Ravi
authors.initials: PR
authors.lastname: Waldron
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA 94304, USA ; Division of Infectious Diseases & Geographic Medicine, Stanford University, Stanford, CA 94305-5107, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016174:Hepacivirus / Q000276:immunology*; D006521:Hepatitis, Chronic / Q000276:immunology / Q000628:therapy*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D011092:Polyethylene Glycols; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; C100416:peginterferon alfa-2a