title: Gene expression patterns that correlate with hepatitis C and early progression to fibrosis in liver transplant recipients.
abstract: OBJECTIVE
  Liver transplant recipients infected with hepatitis C virus (HCV) develop recurrent hepatitis soon after transplantation and, in some cases, progress to fibrosis within the first 2 years. Our goals were to identify molecular processes influencing the liver disease progression and to find potential gene markers of early fibrosis.
  
  
  METHODS
  We performed gene expression profiling on serial liver biopsy specimens obtained from 13 (11 infected and 2 uninfected) transplant recipients within the first year after transplantation at 0, 3, 6, and 12 months. The data were compared with clinical observations and with a gene expression database obtained for 55 nontransplant HCV-infected and uninfected liver samples.
  
  
  RESULTS
  We identified several specific gene expression patterns. The first pattern was unique for the transplant recipients regardless of their infection status. The corresponding genes encoded stress response proteins and blood proteins involved in coagulation that were differentially expressed in response to posttransplantation graft recovery. The second pattern was specific to HCV-infected samples and included up-regulation of genes encoding components of the interferon-mediated antiviral response and immune system (antigen presentation, cytotoxic response). This up-regulation pattern was absent or suppressed in the patients who developed early fibrosis, indicating that the disease progression might result from an impaired liver response to infection. Finally, we identified gene expression patterns that were specific for 12-month biopsy specimens in all 4 HCV-infected patients who developed early fibrosis.
  
  
  CONCLUSIONS
  The identified gene expression patterns may prove useful for diagnostic and prognostic applications in HCV-infected patients, including predicting early progression to fibrosis.
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195-8070, USA.
authors.forename: Maria W
authors.initials: MW
authors.lastname: Smith
authors.forename: Kathie-Anne
authors.initials: KA
authors.lastname: Walters
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Korth
authors.forename: Matthew
authors.initials: M
authors.lastname: Fitzgibbon
authors.forename: Sean
authors.initials: S
authors.lastname: Proll
authors.forename: Jill C
authors.initials: JC
authors.lastname: Thompson
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Shuhart
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Furlong
authors.forename: Paula P
authors.initials: PP
authors.lastname: Cox
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.forename: John D
authors.initials: JD
authors.lastname: Phillips
authors.forename: James P
authors.initials: JP
authors.lastname: Kushner
authors.forename: Nelson
authors.initials: N
authors.lastname: Fausto
authors.forename: Robert L
authors.initials: RL
authors.lastname: Carithers
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D000328:Adult; D017951:Antigen Presentation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000502:physiology; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D007372:Interferons