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

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

K. Katayama et al., Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance, J VIRAL HEP, 8(3), 2001, pp. 180-185

26

INGLESE

Article

Gastroenerology and Hepatology

JOURNAL OF VIRAL HEPATITIS

1352-0504 → ACNP

8

3

2001

180 - 185

ISI

1352-0504(200105)8:3<180:IRTIPP>2.0.ZU;2-K

The aim of this study was to clarify the immunological and virological resp onses to pre-administration of interferon-gamma prior to initiation of inte rferon-alpha treatment in patients with refractory chronic hepatitis C. Twe nty-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/d ay) 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 imm unological 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 th e 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 s ix of 19 patients (end-of treatment response; ETR). Six months after the co mpletion of IFN administration, a virological sustained response (SR) was s een in two of 19 patients. The mean serum levels of IL-10 were significantl y decreased 6 weeks after the start of treatment. Other immunological param eter levels increased significantly during the period of IFN-gamma administ ration, and tended to return to the pretreatment level after the start of I FN-alpha administration. Univariate logistic regression analysis showed tha t 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 en d of the treatment response. These findings suggest that priming with TFN-g amma prior to the initiation of IFN-alpha treatment in patients with refrac tory chronic hepatitis C can modulate the host immune response and this mig ht contribute to viral clearance.