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Hepatic expression of MxA and OAS1 in an ex vivo liver slice assay independently predicts treatment outcomes in chronic hepatitis C
Author(s) -
Cheng J.C.,
Yeh Y.J.,
Huang Y.H.,
Liang K.H.,
Chang M.L.,
Lin C.Y.,
Yeh C.T.
Publication year - 2012
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2011.01538.x
Subject(s) - interferon , liver biopsy , ex vivo , medicine , interferon stimulated gene , hepatitis c , ribavirin , biopsy , gastroenterology , in vivo , immunology , chronic hepatitis , biology , virus , immune system , innate immune system , microbiology and biotechnology
Summary. Antiviral effect of interferon is mediated by the expression of interferon‐stimulated genes (ISGs). However, because of the difficulty in obtaining paired liver biopsies before and after interferon treatment, the key ISGs expressed in human hepatocytes and responsible for interferon‐based antiviral activities in chronic hepatitis C remain illusive. Prior to a standard course of peginterferon plus ribavirin therapy, 104 patients underwent a liver biopsy. A small piece of the liver biopsy sample from each patient was submitted for ex vivo tissue culture in the presence or absence of interferon. Hepatic expression of 8 ISGs was detected by RT‐PCR. The ISG expression patterns and clinicopathological variables were correlated with subsequent treatment outcomes. Multivariate logistic regression analysis showed that hepatic MxA expression ( P = 0.008) and leucocyte count ( P = 0.040) independently predicted the end of therapeutic virological response, while hepatic OAS1 expression ( P = 0.003), genotype 1 ( P = 0.002), HCV‐RNA level ( P = 0.007), AST/ALT ratio ( P = 0.004) and leucocyte count ( P = 0.034) independently predicted the sustained virological response. Immunohistochemistry analysis showed that interferon‐induced OAS1 expression localized to the hepatocytes. In conclusion, hepatic MxA and OAS1 expression predicted, respectively, the end of therapeutic and sustained virological responses in interferon‐based treatment of chronic hepatitis C.