title: Hepatic expression of MxA and OAS1 in an ex vivo liver slice assay independently predicts treatment outcomes in chronic hepatitis C.
abstract: 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.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: J-C
authors.initials: JC
authors.lastname: Cheng
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Yeh
authors.forename: Y-H
authors.initials: YH
authors.lastname: Huang
authors.forename: K-H
authors.initials: KH
authors.lastname: Liang
authors.forename: M-L
authors.initials: ML
authors.lastname: Chang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lin
authors.forename: C-T
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage; D001706:Biopsy; D002478:Cells, Cultured; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D015870:Gene Expression; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000008:administration & dosage; D007372:Interferons / Q000008:administration & dosage*; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D012254:Ribavirin / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012254:Ribavirin; D007372:Interferons; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins