Intrahepatic MxA and PKR protein expression in chronic hepatitis C virus infection

✍ Scribed by Gerry C. MacQuillan; W. Bastiaan de Boer; Michael A. Platten; Kieran A. McCaul; William D. Reed; Gary P. Jeffrey; Jane E. Allan

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 419 KB
• Volume: 68
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.10182

✦ Synopsis

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 liver disease. 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.