Gene expression patterns that correlate with hepatitis C and early progression to fibrosis in liver transplant recipients.
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.
Smith
Maria W
MW
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195-8070, USA.
Walters
Kathie-Anne
KA
Korth
Marcus J
MJ
Fitzgibbon
Matthew
M
Proll
Sean
S
Thompson
Jill C
JC
Yeh
Matthew M
MM
Shuhart
Margaret C
MC
Furlong
Jeffrey C
JC
Cox
Paula P
PP
Thomas
David L
DL
Phillips
John D
JD
Kushner
James P
JP
Fausto
Nelson
N
Carithers
Robert L
RL
Katze
Michael G
MG
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
D007372:Interferons