Hepatic expression of type I interferon receptor for predicting response to interferon therapy in chronic hepatitis C patients: a comparison of immunohistochemical method vs. competitive polymerase chain reaction assay

The focus of this study is to determine both mRNA and protein expression levels of the type I interferon (IFN) receptor subunits, IFNalpha receptor (IFNAR1) and IFNalpha/beta receptor (IFNAR2), in the liver, and to assess which quantification method is most useful in predicting response to IFN in chronic hepatitis C patients. Liver biopsy specimens from 41 chronic hepatitis C patients subsequently treated with IFN were immunostained with IFNAR1 and IFNAR2 antibodies, and also analyzed for both receptor subunit mRNA levels, using competitive polymerase chain reaction. Immunostaining of IFNAR1 and IFNAR2 was observed in the cell membrane and cytoplasm of hepatocytes in all liver specimens. Hepatic expression of IFNAR1 (r = 0.45, P = 0.012) or IFNAR2 mRNA (r = 0.46, P = 0.009) was weakly correlated with their protein expression in hepatocytes. The labeling indexes of IFNAR1 (136.7 +/- 94.1 vs. 77.4 +/- 76.8, P = 0.032) and IFNAR2 (153.1 +/- 80.2 vs. 87.2 +/- 75.5, P = 0.011) in liver specimens were significantly higher in sustained virologic responders (n = 17) than in non-sustained virologic responders (n = 24), while mRNA levels of either receptor subunit did not differ between response groups. These results suggest that protein expression-of the type I IFN receptor in liver is a more useful measure than its mRNA expression in predicting response to IFN in chronic hepatitis C patients. (C) 2002 Elsevier Science B.V. All rights reserved.