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

✍ Scribed by 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

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 340 KB
• Volume: 46
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.21778

✦ Synopsis

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 HIVpositive patients with acute (n ‫؍‬ 52) and chronic (n ‫؍‬ 60) hepatitis C treated with pegylated interferon-␣. 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 (Odds 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.