Table of Contents
Hepatitis Research and Treatment
Volume 2013, Article ID 917261, 6 pages
http://dx.doi.org/10.1155/2013/917261
Clinical Study

Involvement of Differential Relationship between HCV Replication and Hepatic PRR Signaling Gene Expression in Responsiveness to IFN-Based Therapy

1Department of Gastroenterology, Osaka National Hospital, Hoenzaka 2-1-14, Chuo-ku, Osaka 540-0006, Japan
2BML, Inc., Kawagoe 350-1101, Japan
3Department of Gastroenterology, Minamiwakayama National Hospital, Tanabe 646-8558, Japan

Received 12 March 2013; Revised 14 November 2013; Accepted 2 December 2013

Academic Editor: Man-Fung Yuen

Copyright © 2013 Nobukazu Yuki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aim. To gain an insight into the effect of HCV replication-associated interference with the IFN system on hepatic mRNA expression involved in IFN production. Methods. Relative mRNA expression of TLR3/RIG-I signaling genes involved in IFN-β production was correlated with positive- and negative-strand HCV RNAs in pretreatment liver tissues responsive and nonresponsive to peginterferon and ribavirin for chronic hepatitis C genotype 1. Treatment response was analyzed for per protocol population at weeks 12 ( ) and 24 ( ) and at 24 weeks aftertreatment ( ). Results. HCV replication had no relation to the expression of TLR3, RIG-I, TRIF, IPS-1, IRF3, and IFN-β mRNAs in responders. In striking contrast, positive- and/or negative-strand HCV showed positive correlations with TLR3, RIG-I, TRIF, IPS-1, and IRF3 mRNAs in week-12 nonresponders; with RIG-I, TRIF, IPS-1, and IRF3 mRNAs in week-24 nonresponders; and with TLR3, RIG-I, and IRF3 mRNAs in posttreatment nonresponders. Thus mRNA expression of TLR3/RIG-I signaling genes was increased in relation to viral replication in nonresponders. Conclusions. The findings in IFN nonresponders may imply a host feedback response to severe impairment of the IFN system associated with HCV replication.