title: Intrahepatic MxA and PKR protein expression in chronic hepatitis C virus infection.
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.
authors.affiliation: Department of Medicine, The University of Western Australia, Australia. gmacq@cyllene.uwa.edu.au
authors.forename: Gerry C
authors.initials: GC
authors.lastname: MacQuillan
authors.forename: W Bastiaan
authors.initials: WB
authors.lastname: de Boer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Platten
authors.forename: Kieran A
authors.initials: KA
authors.lastname: McCaul
authors.forename: William D
authors.initials: WD
authors.lastname: Reed
authors.forename: Gary P
authors.initials: GP
authors.lastname: Jeffrey
authors.forename: Jane E
authors.initials: JE
authors.lastname: Allan
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D019204:GTP-Binding Proteins; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012254:Ribavirin; D019892:eIF-2 Kinase; D019204:GTP-Binding Proteins