Plasma IL-6 and IL-9 predict the failure of interferon-α plus ribavirin therapy in HIV/HCV-coinfected patients

J Antimicrob Chemother. 2012 May;67(5):1238-45. doi: 10.1093/jac/dkr595. Epub 2012 Jan 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Female
  • Follow-Up Studies
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interleukin-6 / blood*
  • Interleukin-9 / blood*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Ribavirin / administration & dosage*
  • Treatment Failure
  • Viral Load

Substances

  • Antiviral Agents
  • IL6 protein, human
  • IL9 protein, human
  • Interferon-alpha
  • Interleukin-6
  • Interleukin-9
  • Ribavirin