title: HCV RNA levels in a multiethnic cohort of injection drug users: human genetic, viral and demographic associations.
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 log(10) 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.
  
  
  CONCLUSIONS
  The level of HCV viremia is influenced by a large number of demographic, viral, and human genetic factors.
authors.affiliation: Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Uccellini
authors.forename: Fan-Chen
authors.initials: FC
authors.lastname: Tseng
authors.forename: Alessandro
authors.initials: A
authors.lastname: Monaco
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Shebl
authors.forename: Ruth
authors.initials: R
authors.lastname: Pfeiffer
authors.forename: Myhanh
authors.initials: M
authors.lastname: Dotrang
authors.forename: Dianna
authors.initials: D
authors.lastname: Buckett
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Brian R
authors.initials: BR
authors.lastname: Edlin
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D015995:Prevalence; D012367:RNA, Viral / Q000235:genetics*; D018570:Risk Assessment; D012737:Sex Factors; D018709:Statistics, Nonparametric; D015819:Substance Abuse, Intravenous / Q000208:ethnology / Q000503:physiopathology / Q000821:virology*; D014505:Urban Population; D019562:Viral Load; D014766:Viremia / Q000208:ethnology / Q000235:genetics / Q000821:virology; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda