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Attenuation of Responsiveness to Interferon-α Treatment by Preceded Overactivation of Interferon-mediated Pathway in Patients Chronically Infected by Hepatitis C Virus


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Title: Attenuation of Responsiveness to Interferon-α Treatment by Preceded Overactivation of Interferon-mediated Pathway in Patients Chronically Infected by Hepatitis C Virus
Authors: Nakata, Keisuke / Nakao, Kazuhiko / Morikawa, Takashi / Inokuchi, Kaoru / Hamasaki, Keisuke / Tsuruta, Shotaro / Kato, Yuji / Yatsuhashi, Hiroshi / Kusumoto, Yukio / Ishii, Nobuko / Eguchi, Katsumi
Issue Date: 20-Dec-2000
Citation: Acta medica Nagasakiensia. 2000, 45(3-4), p.15-19
Abstract: 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.
Keywords: interferon treatment / chronic hepatitis C / inter feron regulatory factor-1 / interferon regulatory factor-2 / hepatitis C virus
URI: http://hdl.handle.net/10069/16165
ISSN: 00016055
Type: Departmental Bulletin Paper
Text Version: publisher
Appears in Collections:Volume 45, No. 3-4

Citable URI : http://hdl.handle.net/10069/16165

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