MxA induction may predict sustained virologic responses of chronic hepatitis B patients with IFN-alpha treatment.
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.
Kong
Xiao-Fei
XF
Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Zhang
Xin-Xin
XX
Gong
Qi-Ming
QM
Gao
Jian
J
Zhang
Shen-Ying
SY
Wang
Lin
L
Xu
Jie
J
Han
Yue
Y
Jin
Gen-Di
GD
Jiang
Jie-Hong
JH
Zhang
Dong-Hua
DH
Lu
Zhi-Meng
ZM
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
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