Intrahepatic MxA and PKR Protein Expression in Chronic Hepatitis C Virus Infection

G.C. Macquillan, W.B. De Boer, M.A. Platten, Kieran Mccaul, W.D. Reed, G.P. Jeffrey, J.E. Allan

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38 Citations (Scopus)

Abstract

The therapeutic effect of interferon-alpha and ribavirin in the treatment of chronic hepatitis C viral infection is limited. To identify patient characteristics that may predict responsiveness to treatment, the intrahepatic protein expression of two directly induced IFN-alpha effector proteins, MxA and PKR, were studied. Forty liver biopsy samples from patients with a variety of chronic liver diseases were stained for MxA and PKR protein using immunohistochemical techniques. In a HCV patient cohort, 30 liver biopsies were stained for MxA and PKR protein prior to treatment with IFN-alpha and ribavirin. PKR protein expression was not upregulated in viral liverdisease. In contrast, MxA protein expression was significantly upregulated in viral liver disease (P=0.005). In chronic HCV liver disease, moderate to strong cytoplasmic expression of MxA protein was observed in hepatocytes and monocytes, indicating endogenous hepatocellular IFN-alpha pathway activation. In the HCV patient cohort treated with combination therapy, strong pre-treatment MxA hepatocyte expression was predictive of a non-response to treatment (odds ratio 9.33; P=0.01; 95% confidence interval 1.63-53.2). This effect was independent of HCV genotype and viral load. It is concluded that pretreatment hepatocellular MxA expression may become a useful predictor of response to combination treatment with IFN-alpha and ribavirin. (C) 2002 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)197-205
JournalJournal of Medical Virology
Volume68
Issue number2
DOIs
Publication statusPublished - 2002

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