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.
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Authors | K 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 |
Journal | Journal of viral hepatitis
(J Viral Hepat)
Vol. 8
Issue 3
Pg. 180-5
(May 2001)
ISSN: 1352-0504 [Print] England |
PMID | 11380795
(Publication Type: Clinical Trial, Journal Article)
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Chemical References |
- Antiviral Agents
- CD4 Antigens
- CD8 Antigens
- Cytokines
- Interferon-alpha
- RNA, Viral
- beta 2-Microglobulin
- Neopterin
- Interferon-gamma
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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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