Identification of novel markers for liver fibrosis in HIV/hepatitis C virus coinfected individuals using genomics-based approach.
OBJECTIVE
The degree of liver fibrosis is a determinant for initiation of therapy for hepatitis C virus. Liver biopsy is invasive, risky and costly, but is required to assess fibrosis. This study intended to identify novel noninvasive markers to accurately assess fibrosis in HIV/hepatitis C virus coinfection.


METHODS
Using 100 biopsies from 68 HIV/hepatitis C virus coinfected patients, we developed a predictive model consisting of six serum markers along with age and antiretroviral therapy experience. DNA microarray analysis of peripheral blood mononuclear cells associated with a subset of 51 biopsies obtained from 28 patients was performed and incorporated into a second model.


RESULTS
The eight-marker model yielded an area under the receiver operating characteristic curve of 0.904. Combined analysis of clinical and DNA microarray data in the 51-biopsy subset identified two genes (alanine amino peptidase-N and mitogen-activated protein kinase kinase-3) that predicted fibrosis with high significance. The four-marker model that included the two genes and two serum markers had an area under the receiver operating characteristic curve of 0.852, which did not differ significantly from the eight-marker model on this subset (area under the receiver operating characteristic curve = 0.856, P = 0.96).


CONCLUSIONS
Both models accurately predicted fibrosis with an accuracy of 87.9%, thereby sparing 83% of patients from obtaining a biopsy. DNA microarray analysis can be invaluable in identifying novel biomarkers of liver fibrosis.
Suzman
Daniel L
DL
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
McLaughlin
Mary
M
Hu
Zonghui
Z
Kleiner
David E
DE
Wood
Brad
B
Lempicki
Richard A
RA
Mican
Joann M
JM
Suffredini
Anthony
A
Masur
Henry
H
Polis
Michael A
MA
Kottilil
Shyam
S
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018826:CD13 Antigens / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012720:Severity of Illness Index
D015415:Biomarkers; D048052:Mitogen-Activated Protein Kinase 3; D018826:CD13 Antigens