Attenuation of Responsiveness to Interferon-α Treatment by Preceded Overactivation of Interferon-mediated Pathway in Patients Chronically Infected by Hepatitis C Virus
The Interferon (IFN) receptor-mediated signal transduction pathways involve the two novel DNA-binding factors, interferon regulatory factor-1 (IRF-1) and IRF-2. Both recognize the same DNA sequence, in which the expression ratio of IRF-1 to IRF-2 is relevant to induction of IFN-inducible genes, because IRF-1 acts as a transcriptional activator and IRF-2 as a counterpart. In the present study, 54 patients with chronic hepatitis C and the age-and sex-matched 7 subjects with fatty liver as a control were subjected to analysis of the expression ratio of IRF-1 to IRF-2 mRNA in the liver tissue obtained at the time of livert biopsy by reverse transcription-polymerase chain reaction in combination with a restriction fragment length polymorphism assay. The expression ratio of IRF-1 to IRF-2 mRNA in the liver tissue in patients chronically infected by hepatitis C virus (HCV) was significantly higher than that in control, although the values did not correlate with the serum levels of HCV-RNA. Of 54 patients, 28 received IFN treatment, resulting in complete response in 8 patients. With respect to responsiveness to IFN treatment, patients who had complete response had the relatively lower ratios of IRF-1 to IRF-2 mRNA in the liver tissue, compared with those who did not. These results indicate that the IFN-mediated pathway is spontaneously activated in patients with chronic hepatitis C, and that its preceded overactivation counteracts on the efficacy of IFN treatment in these patients
