RESUMO
Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.
Assuntos
Infecções por HIV/complicações , Hepatite C/genética , Hepatite C/virologia , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/genética , Hepacivirus/genética , Humanos , Interferons , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Análise de Regressão , Resultado do TratamentoRESUMO
UNLABELLED: Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) coinfection poses a difficult therapeutic problem. Response to HCV-specific therapy is variable but might be influenced by host genetic factors, including polymorphisms of cytokine genes. Here, we studied whether interleukin-6 (IL-6) C174G gene polymorphism affects the response to antiviral treatment in HCV-infected HIV-positive subjects. We determined IL-6 genotypes in HIV-positive patients with acute (n = 52) and chronic (n = 60) hepatitis C treated with pegylated interferon-alpha. Two hundred ten HCV monoinfected, 197 HIV monoinfected, and 100 healthy individuals were studied as controls. Patients were classified into high and low producers according to IL-6 genotypes. Rates of sustained virological responses (SVRs) were compared between the IL-6 genotypes. Signal transducer and activator of transcription three phosphorylation was analyzed by Western blot in HCV core-transfected human hepatoma cell line (HUH7) cells. Distribution of IL-6 genotypes did not differ significantly between the study groups. SVR was achieved in 63% of HIV/HCV coinfected patients. Carriers of the IL-6 high producer (HP) genotype had significantly higher SVR rates than patients with an IL-6 low producer genotype (70.1% versus 52%; P < 0.002). This effect was seen in both HIV-positive patients with acute (74% versus 33%; P < 0.05) and chronic (66% versus 33%; P < 0.05) hepatitis C. Multivariate analysis confirmed IL-6 HP carriage as an independent positive predictor for SVR (Odd's ratio 6.1; P = 0.004). This effect corresponds to the in vitro observation that in HCV core-transfected HUH7 cells, IL-6 overcomes the HCV core-mediated inhibition of STAT3 activation. CONCLUSION: Response rates to HCV-specific treatment are higher in HCV/HIV-positive patients carrying the IL-6 HP genotype, which might be because of IL-6 mediated STAT3 activation.