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