title: Plasma IL-6 and IL-9 predict the failure of interferon-α plus ribavirin therapy in HIV/HCV-coinfected patients.
abstract: BACKGROUND
  The cytokine profile plays an important role in treatment outcome of hepatitis C virus (HCV) infection, and probably modulates the immune response against HCV. The aim of this study was to evaluate which cytokines affect the response to interferon-α (IFN-α) and ribavirin therapy and how these cytokines change 72 weeks after starting anti-HCV therapy in HIV/HCV-coinfected patients.
  
  
  METHODS
  We carried out a retrospective follow-up study of 65 patients on anti-HCV therapy. A sustained virological response (SVR) was defined as an undetectable HCV viral load up to 24 weeks after the end of treatment. Cytokines were measured using a multiplex immunoassay kit.
  
  
  RESULTS
  On starting anti-HCV therapy, non-responder (NR) patients had higher levels of interleukin (IL)-6, IL-9, IL-10 and tumour necrosis factor (TNF)-α (P < 0.05), while IL-17A levels were increased in SVR patients (P = 0.058). However, only patients with high levels of IL-6 and IL-9 had decreased odds to achieve SVR (P < 0.05). Plasma levels of IL-6 and IL-9 had a high predictive value for SVR failure [area under the ROC curve (AUC) 0.839 (95% CI 0.733-0.945) and AUC 0.769 (95% CI 0.653-0.884)]. In addition, during anti-HCV therapy, IL-1β showed an increase in NR patients (P = 0.015) and IL-10 decreased in SVR patients (P = 0.049). After clearing HCV infection, low levels of TNF-α, IL-6, IL-9, IL-10, IL-13 and IL-22 were found in SVR patients (P < 0.05), as well as IL-1β, but only near statistical significance (P = 0.073).
  
  
  CONCLUSIONS
  High plasma levels of IL-6 and IL-9 had a high predictive value for SVR failure. Furthermore, clearing of HCV infection was associated with low inflammatory and T helper (Th)2/Th9/Th22 cytokine levels.
authors.affiliation: Laboratorio de Epidemiología Molecular de Enfermedades Infecciosas, Centro Nacional de Microbiología,  Instituto de Salud Carlos III, Majadahonda, Madrid,  Spain.
authors.forename: María
authors.initials: M
authors.lastname: Guzmán-Fulgencio
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Jiménez
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López
authors.forename: Jaime
authors.initials: J
authors.lastname: Cosín
authors.forename: Pilar
authors.initials: P
authors.lastname: Miralles
authors.forename: Dariela
authors.initials: D
authors.lastname: Micheloud
authors.forename: Ma Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood*; D016906:Interleukin-9 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; C508600:IL6 protein, human; C508607:IL9 protein, human; D016898:Interferon-alpha; D015850:Interleukin-6; D016906:Interleukin-9; D012254:Ribavirin