RESUMO
UNLABELLED: 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. CONCLUSION: The level of HCV viremia is influenced by a large number of demographic, viral, and human genetic factors.
Assuntos
Hepacivirus/genética , Hepatite C Crônica/genética , Interleucinas/genética , RNA Viral/genética , Abuso de Substâncias por Via Intravenosa/virologia , Adulto , Fatores Etários , Estudos de Coortes , Feminino , Genótipo , Infecções por HIV/etnologia , Infecções por HIV/genética , Hepatite C Crônica/etnologia , Humanos , Interferons , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Abuso de Substâncias por Via Intravenosa/etnologia , Abuso de Substâncias por Via Intravenosa/fisiopatologia , População Urbana , Carga Viral , Viremia/etnologia , Viremia/genética , Viremia/virologia , Adulto JovemRESUMO
Among 1369 Urban Health Study participants, we evaluated genetic models for the association of IL28B genotype (rs12979860 and rs8099917) with hepatitis C virus (HCV) clearance. For rs12979860, adjusted odds ratios for spontaneous HCV clearance were as follows: IL28B-CC, 3.88 (P < .001); IL28B-CT, 1.48 (P = .08). On the basis of Akaike information criteria values and χ(2) tests, a supra-additive (quadratic) model fit these data best. Models based on rs8099917 provided poorer fit. Evidence that a supra-additive rs12979860-based model best fits the association of IL28B-genotype with HCV clearance may improve clinical prediction models and foster a better understanding of functional mechanisms underlying this association.