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

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

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

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

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.

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

J Nattermann,M Vogel,T Berg,M Danta,B Axel,C Mayr,R Bruno,C Tural,G Klausen,B Clotet,T Lutz,F ,M Rausch,HD Nischalke,K Schewe,B Bienek,G Haerter,T Sauerbruch,JK Rockstroh,U Spengler, ,

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Hepatology (Baltimore, Md.)

VOLUME: 46

Page Numbers: 1016-25

Journal Abbreviation: Hepatology

ISSN: 0270-9139

DAY: 30

MONTH: Oct

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 8302946

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

AFFILIATION: Department of Internal Medicine I, University of Bonn, Bonn, Germany. Jacob.Nattermann@ukb.uni-bonn.de

Country: United States

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MEDLINETA: Hepatology

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