title: MxA induction may predict sustained virologic responses of chronic hepatitis B patients with IFN-alpha treatment.
abstract: The objective of this study was to find potential biomarkers for predicting sustained virologic responses to interferon-alpha (IFN-alpha) treatment in chronic hepatitis B (CHB) patients. A total of 101 CHB patients were treated with pegylated IFN-alpha2a for 48 weeks and followed up for 24 weeks, including 34 IFN responders (IFN-Rs) and 67 IFN nonresponders (IFN-NRs). After peripheral blood mononuclear cells (PBMCs) and Epstein-Barr virus-transferred B (EBV-B) cell lines were treated with different concentrations of IFN-alpha in vitro, activated IFN-stimulated gene factor3 (ISGF3) and IFN-gamma-activation factor (GAF) were measured by EMSA, and MxA, OAS1, and PKR mRNA were measured by real-time PCR. Polymorphisms in the MxA promoter were genotyped to find the possible association. IFN-alpha-activated ISGF3 and GAF levels were similar between IFN-NRs and IFN-Rs. However, MxA mRNA induction in IFN-Rs was higher than that in IFN-NRs, and such discrepancy increased when highly concentrated IFN was used to stimulate. The OAS1 and PKR mRNA induction have a similar pattern between IFN-Rs and IFN-NRs. In addition, frequency of the MxA-88G/T genotype was significantly different between IFN-Rs and IFN-NRs, and this polymorphism was also functional because MxA mRNA induction in patients with GG genotype was lower than those with GT genotype. Regression analysis showed that MxA mRNA induction after 10,000 IU/mL IFN stimulation could serve as an independent factor for predicting IFN-alpha, with an area under curve (AUC) of 0.838, a positive predictive value of 68% for IFN-Rs, and a negative predictive value of 89% for IFN-NRs. MxA mRNA induced by IFN-alpha might predict sustained virologic responses to IFN-alpha treatment in CHB patients.
authors: Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors: Xiao-Fei
authors: XF
authors: Kong
authors: Xin-Xin
authors: XX
authors: Zhang
authors: Qi-Ming
authors: QM
authors: Gong
authors: Jian
authors: J
authors: Gao
authors: Shen-Ying
authors: SY
authors: Zhang
authors: Lin
authors: L
authors: Wang
authors: Jie
authors: J
authors: Xu
authors: Yue
authors: Y
authors: Han
authors: Gen-Di
authors: GD
authors: Jin
authors: Jie-Hong
authors: JH
authors: Jiang
authors: Dong-Hua
authors: DH
authors: Zhang
authors: Zhi-Meng
authors: ZM
authors: Lu
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D051379:Mice; D064547:Myxovirus Resistance Proteins; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D019204:GTP-Binding Proteins; C100416:peginterferon alfa-2a