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

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 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. (HEPATOLOGY 2007;46:1016-1025.) Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus; interferon alpha; pegylated interferon alpha; SVR, sustained virological response. From the

Effect of interleukin-6 and insulin resistance on early virological response of Egyptian chronic hepatitis C patients to combined pegylated interferon plus ribavirin therapy

“…These findings were in agreement with the results of Nattermann et al [10], who reported that a higher level of IL-6 is significantly associated with SVR compared with a lower level. In contrast, Cotler et al [17] reported that there was no significant difference in basal IL-6 levels between the groups of responders and nonresponders to IFN therapy.…”

“…Thus, individuals can be classified into high (genotypes IL-6-174 GG and IL-6 -174 GC) and low (genotype IL-6-174 CC) IL-6 producers [9]. This polymorphism has been associated with response to HCV-specific treatment [10].…”

Protein-protein interaction network and mechanism analysis of hepatitis C

“…Moreover, the effect of IL6 C174G gene polymorphisms on the treatment of acute and chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients has been reported previously (Nattermann et al, 2007), confirming our results. IL6, a major proinflammatory cytokine, is produced in various tissues, including activated leukocytes, adipocytes, and endothelial cells (Pradhan et al, 2001).…”

Serum Interleukin-6 Concentration Associated with Response to Therapy for Chronic Hepatitis C Patients

“…Also this finding were in agreement with the results of Faisal et al [17] and Nattermann et al [18] who reported that a higher level of IL-6 is significantly associated with SVR compared with a lower level. In contrast, Cotler et al [19] reported that there was no significant difference in basal IL-6 levels between the groups of responders and non-responders to IFN therapy.…”