title: CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study.
abstract: OBJECTIVE
  There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR.
  
  
  METHODS
  Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment.
  
  
  RESULTS
  Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 10(7) IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 10(7) IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%).
  
  
  CONCLUSIONS
  Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan ; Department of Medicine, National Yang-Ming University Hospital, I-Lan, Taiwan.
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Lee
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Su
authors.forename: Yuan-Jen
authors.initials: YJ
authors.lastname: Wang
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.forename: Kuei-Chuan
authors.initials: KC
authors.lastname: Lee
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use; D054370:Chemokine CXCL9 / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D054370:Chemokine CXCL9; D016207:Cytokines; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a