Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients

Jacob Nattermann, Martin Vogel, Thomas Berg, Mark Danta, Baumgarten Axel, Christoph Mayr, Raffaele Bruno, Christina Tural, Gerd Klausen, Bonaventura Clotet, Thomas Lutz, Frank Grünhage, Michael Rausch, Hans Dieter Nischalke, Knud Schewe, Bernhard Bienek, Georg Haerter, Tilman Sauerbruch, Juergen K. Rockstroh, Ulrich Spengler

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Abstract

Hepatitis C virus (HCV)/human immunodeficirency 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-α. 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.

Original languageEnglish
Pages (from-to)1016-1025
Number of pages10
JournalHepatology
Volume46
Issue number4
DOIs
Publication statusPublished - Oct 2007

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ASJC Scopus subject areas

  • Hepatology

Cite this

Nattermann, J., Vogel, M., Berg, T., Danta, M., Axel, B., Mayr, C., Bruno, R., Tural, C., Klausen, G., Clotet, B., Lutz, T., Grünhage, F., Rausch, M., Nischalke, H. D., Schewe, K., Bienek, B., Haerter, G., Sauerbruch, T., Rockstroh, J. K., & Spengler, U. (2007). Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients. Hepatology, 46(4), 1016-1025. https://doi.org/10.1002/hep.21778