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Intrahepatic MxA and PKR protein expression in chronic hepatitis C virus infection
Author(s) -
MacQuillan Gerry C.,
de Boer W. Bastiaan,
Platten Michael A.,
McCaul Kieran A.,
Reed William D.,
Jeffrey Gary P.,
Allan Jane E.
Publication year - 2002
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.10182
Subject(s) - ribavirin , protein kinase r , hepatitis c virus , medicine , alpha interferon , virology , liver disease , interferon , liver biopsy , hepatitis c , antiviral protein , hepacivirus , immunology , virus , biology , biopsy , gene , rna , cancer , biochemistry , cell cycle , cyclin dependent kinase 2
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 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. J. Med. Virol. 68:197–205, 2002. © 2002 Wiley‐Liss, Inc.