Interferon-antibodies and the breakthrough phenomenon during ribavirin/interferon-alpha combination therapy and interferon-alpha monotherapy of patients with chronic hepatitis C

Z Gastroenterol. 1999 Aug;37(8):715-23.

Abstract

Background/aims: The significance of interferon antibodies with respect to response to treatment in patients with chronic hepatitis C treated with interferon-alpha (INF-alpha) remains a matter of debate. The influence of ribavirin on IFN-antibody formation in combination therapy with IFN-alpha has not yet been studied. Therefore we evaluated the relationship between IFN-antibodies and response to ribavirin/IFN-alpha combination therapy and IFN-alpha monotherapy.

Methods: We studied 169 patients with chronic hepatitis C who were treated either with IFN alpha 2a (6 MU, thrice weekly) alone or in combination with ribavirin (14 mg/kg per day) for twelve weeks. Thereafter, patients who achieved a virological response (HCV-RNA-negative) were treated with 3 MU IFN-alpha thrice weekly for another 40 weeks. IFN antibodies were analyzed and quantified by a double-antigen sandwich enzyme immunoassay (EIA). In 86 patients two neutralization assays--an antiviral neutralization assay as well as an antiproliferative neutralization assay--were performed in addition. The relationship of the development of IFN-antibodies with the virologically defined response to treatment was analyzed.

Results: Ribavirin did neither influence the prevalence nor the level of IFN-antibodies. The frequencies of IFN-antibody formation did not differ in the response groups. However, patients with breakthrough showed significantly higher IFN-antibody titers as compared to responder at end of treatment (median 1,336 BU/ml vs. 148 BU/ml; p = 0.018). Among the breakthrough patients those with IFN-antibodies showed the reappearance of HCV-RNA during therapy significantly earlier (median week 24) than those without IFN-antibodies (median week 32; p = 0.03).

Conclusion: The addition of ribavirin to IFN-alpha does not influence the formation of IFN-antibodies. The development of high-titer IFN-antibodies during IFN-alpha or ribavirin/IFN-alpha therapy of patients with chronic hepatitis C may account for the early occurrence of breakthrough in some patients, while other mechanisms seem to be responsible for this phenomenon in the majority of the afflicted patients.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies / blood*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / immunology
  • Drug Therapy, Combination
  • Female
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects*
  • Interferon-alpha / immunology
  • Interferons / immunology*
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Ribavirin / administration & dosage
  • Ribavirin / adverse effects*
  • Treatment Outcome

Substances

  • Antibodies
  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Ribavirin
  • Interferons