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AIDS. 2008 Jul 31;22(12):1433-9. doi: 10.1097/QAD.0b013e328304dfe7.

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

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Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.



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.


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.


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).


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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