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

• Published in: Hepatology (Baltimore, Md.) Vol. 46; no. 4; pp. 1016 - 1025
• Main Authors: Nattermann, Jacob, Vogel, Martin, Berg, Thomas, Danta, Mark, Axel, Baumgarten, Mayr, Christoph, Bruno, Raffaele, Tural, Christina, Klausen, Gerd, Clotet, Bonaventura, Lutz, Thomas, Grünhage, Frank, Rausch, Michael, Nischalke, Hans Dieter, Schewe, Knud, Bienek, Bernhard, Haerter, Georg, Sauerbruch, Tilman, Rockstroh, Juergen K., Spengler, Ulrich
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2007
• Subjects: Acute Disease; Adult; Aged; Antiviral Agents - therapeutic use; Cell Line, Tumor; Chronic Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Genotype; Hepatitis C - complications; Hepatitis C - drug therapy; Hepatitis C - genetics; HIV Infections - complications; Humans; Interferon-alpha - therapeutic use; Interleukin-6 - genetics; Interleukin-6 - metabolism; Male; Middle Aged; Polyethylene Glycols - therapeutic use; Polymorphism, Single Nucleotide - genetics; Recombinant Proteins; Ribavirin - therapeutic use; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Treatment Outcome
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.21778

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. (HEPATOLOGY 2007.)