The Initial Study On The Relationship Between No Response To Interferon Alpha Treatment In Chronic Hepatitis Band Liver Differential Gene Expression

Objective: To screen the differentially expressed genes between responders(Rs) and nonresponders(NRs) in CHB patients treated with IFN-α, and to explore the molecular basis for treatment failure.Methods: Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy.Gene expression levels were compared between 7 NRs and 6 Rs,Gene Ontology category and KEGG pathway were analyzed for differentially expressed genes, and the selected differentially expressed genes were confirmed using real-time polymerase chain reaction.Results: We identified 3592 genes whose expression levels differed significantly between all Rs and NRs (P <0 .05); many of these genes are IFN stimulated genes(ISGs) and immune related genes.The ISGs are more highly expressed while immune related genes are inhibited in NRs before IFN-αtreatment.Two ISGs(CEB1 and USP18) which are linked in an IFN-inhibitory pathway are highly expressed in NRs, and a potential antiviral gene ISG20 is inhibited in NRs, suggesting a possible rationale for treatment non-response.Conclusions: NRs and Rs have different liver gene expression profiles before IFN-αtreatment. Preactivation of the IFN signaling pathway leading to the increased expression of inhibitory ISGs and inhibition of immune response in the pretreatment livers were associated with NRs.