Immunological response to interferon-γ priming prior to interferon-α treatment in refractory chronic hepatitis C in relation to viral clearance

• Published in: Journal of viral hepatitis 2001-05, Vol.8 (3), p.180-185
• Main Authors: Katayama, K., Kasahara, A., Sasaki, Y., Kashiwagi, T., Naito, M., Masuzawa, M., Katoh, M., Yoshihara, H., Kamada, T., Mukuda, T., Hijioka, T., Hori, M., Hayashi, N.
• Format: Article
• Language: English
• Subjects: Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; beta 2-Microglobulin - blood; CD4 Antigens - blood; CD8 Antigens - blood; Cytokines - blood; Drug Administration Schedule; Female; Hepacivirus - genetics; Hepacivirus - immunology; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - virology; Humans; IL-10; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-gamma - administration & dosage; Interferon-gamma - adverse effects; Logistic Models; Male; Middle Aged; Neopterin - blood; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - chemistry; RNA, Viral - isolation & purification; Th1 cytokine; Th2 cytokine; Viral Load
• ISSN: 1352-0504; 1365-2893
• DOI: 10.1046/j.1365-2893.2001.00274.x

The aim of this study was to clarify the immunological and virological responses to pre‐administration of interferon‐γ prior to initiation of interferon‐α treatment in patients with refractory chronic hepatitis C. Twenty‐two nonresponders to 6‐months of IFN‐α treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN‐γ (1 MIU/day) was administered daily for 14 days followed by natural IFN‐α (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‐γ, TNF‐α, 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‐α 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‐γ administration, and tended to return to the pretreatment level after the start of IFN‐α 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‐γ prior to the initiation of IFN‐α treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.