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Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance.

Abstract
The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-gamma prior to initiation of interferon-alpha treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-alpha treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-gamma (1 MIU/day) was administered daily for 14 days followed by natural IFN-alpha (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-alpha treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-gamma administration, and tended to return to the pretreatment level after the start of IFN-alpha administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-gamma prior to the initiation of IFN-alpha treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.
AuthorsK Katayama, A Kasahara, Y Sasaki, T Kashiwagi, M Naito, M Masuzawa, M Katoh, H Yoshihara, T Kamada, T Mukuda, T Hijioka, M Hori, N Hayashi
JournalJournal of viral hepatitis (J Viral Hepat) Vol. 8 Issue 3 Pg. 180-5 (May 2001) ISSN: 1352-0504 [Print] England
PMID11380795 (Publication Type: Clinical Trial, Journal Article)
Chemical References
  • Antiviral Agents
  • CD4 Antigens
  • CD8 Antigens
  • Cytokines
  • Interferon-alpha
  • RNA, Viral
  • beta 2-Microglobulin
  • Neopterin
  • Interferon-gamma
Topics
  • Antiviral Agents (administration & dosage, adverse effects)
  • CD4 Antigens (blood)
  • CD8 Antigens (blood)
  • Cytokines (blood)
  • Drug Administration Schedule
  • Female
  • Hepacivirus (genetics, immunology)
  • Hepatitis C, Chronic (drug therapy, immunology, virology)
  • Humans
  • Interferon-alpha (administration & dosage, adverse effects)
  • Interferon-gamma (administration & dosage, adverse effects)
  • Logistic Models
  • Male
  • Middle Aged
  • Neopterin (blood)
  • RNA, Viral (chemistry, isolation & purification)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Viral Load
  • beta 2-Microglobulin (blood)

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