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Identification of novel markers for liver fibrosis in HIV/hepatitis C virus coinfected individuals using genomics-based approach.

AbstractOBJECTIVE:
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.
AuthorsDaniel 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
JournalAIDS (London, England) (AIDS) Vol. 22 Issue 12 Pg. 1433-9 (Jul 31 2008) ISSN: 1473-5571 [Electronic] England
PMID18614866 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Validation Study)
Chemical References
  • Biomarkers
  • Mitogen-Activated Protein Kinase 3
  • CD13 Antigens
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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