HCV RNA levels in a multiethnic cohort of injection drug users: Human genetic, viral and demographic associations§

Authors

  • Lorenzo Uccellini,

    1. Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD
    2. Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Milan, Italy
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    • These authors contributed equally to this work.

  • Fan-Chen Tseng,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
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    • These authors contributed equally to this work.

  • Alessandro Monaco,

    1. Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD
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  • Fatma M. Shebl,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
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  • Ruth Pfeiffer,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
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  • Myhanh Dotrang,

    1. Computer Sciences Corporation, Rockville, MD
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  • Dianna Buckett,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
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  • Michael P. Busch,

    1. University of California, San Francisco, CA
    2. Blood Systems Research Institute, San Francisco, CA
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  • Ena Wang,

    1. Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD
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  • Brian R. Edlin,

    1. University of California, San Francisco, CA
    2. SUNY Downstate College of Medicine, Brooklyn, NY, and Center for the Study of Hepatitis C, Weill Medical College of Cornell University, New York, NY
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  • Francesco M. Marincola,

    1. Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD
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  • Thomas R. O'Brien

    Corresponding author
    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
    • Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 5052, Bethesda, MD 20892===

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    • fax: 301-480-1917


  • Potential conflict of interest: Dr. Busch consults for, advises, is on the speakers' bureau for, and received compensation from Gen-Probe. He consults for, advises, is on the speakers' bureau of, and received grants from CaridanBCT and Chiron/Novartis. He consults for, advises, and is on the speakers' bureau of Abbott. He advises and is on the speakers' bureau of Merck and Ortho Diagnostics.

  • This research was supported by the Intramural Research Program of the National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institutes of Health [NIH] Clinical Center) and by federal funds from the National Cancer Institute (contracts NO1-CO-12400 and N02-CP-91027). This work was also supported by NIH grants (R01-DA09532, R01-DA12109, R01-DA13245, and R01-DA16159), a grant from the Substance Abuse and Mental Health Services Administration (H79-TI12103; Center for Substance Abuse Treatment), and the City and County of San Francisco Department of Public Health.

  • §

    The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

Abstract

In patients with chronic hepatitis C, the hepatitis C virus (HCV) RNA level is an important predictor of treatment response. To explore the relationship of HCV RNA with viral and demographic factors, as well as IL28B genotype, we examined viral levels in an ethnically diverse group of injection drug users (IDUs). Between 1998 and 2000, the Urban Health Study (UHS) recruited IDUs from street settings in San Francisco Bay area neighborhoods. Participants who were positive by HCV enzyme immunoassay were tested for HCV viremia by a branched-chain DNA assay. HCV genotype was determined by sequencing the HCV nonstructural 5B protein region. For a subset of participants, IL28B rs12979860 genotype was determined by Taqman. Among 1,701 participants with HCV viremia, median age was 46 years and median duration of injection drug use was 26 years; 56.0% were African American and 34.0% were of European ancestry (non-Hispanic). Human immunodeficiency virus type 1 (HIV-1) prevalence was 13.9%. The overall median HCV RNA level was 6.45 log10 copies/mL. In unadjusted analyses, higher levels were found with older age, male gender, African-American ancestry, hepatitis B virus infection, HIV-1 infection, and IL28B rs12979860-CC genotype; compared to participants infected with HCV genotype 1, HCV RNA was lower in participants with genotypes 3 or 4. In an adjusted analysis, age, gender, racial ancestry, HIV-1 infection, HCV genotype, and IL28B rs12979860 genotype were all independently associated with HCV RNA. Conclusion: The level of HCV viremia is influenced by a large number of demographic, viral, and human genetic factors. (HEPATOLOGY 2012;56:86–94)

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