Abstract | 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). CONCLUSION: 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.
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Authors | Daniel L Suzman, Mary McLaughlin, Zonghui Hu, David E Kleiner, Brad Wood, Richard A Lempicki, Joann M Mican, Anthony Suffredini, Henry Masur, Michael A Polis, Shyam Kottilil |
Journal | AIDS (London, England)
(AIDS)
Vol. 22
Issue 12
Pg. 1433-9
(Jul 31 2008)
ISSN: 1473-5571 [Electronic] England |
PMID | 18614866
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Validation Study)
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Chemical References |
- Biomarkers
- Mitogen-Activated Protein Kinase 3
- CD13 Antigens
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Topics |
- Adult
- Biomarkers
(blood)
- Biopsy
- CD13 Antigens
(genetics)
- Female
- Gene Expression Profiling
(methods)
- Genomics
- HIV Infections
(complications)
- Hepatitis C, Chronic
(complications)
- Humans
- Liver
(pathology)
- Liver Cirrhosis
(diagnosis, genetics, virology)
- Male
- Middle Aged
- Mitogen-Activated Protein Kinase 3
(genetics)
- Models, Statistical
- Oligonucleotide Array Sequence Analysis
(methods)
- Severity of Illness Index
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