title: High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B.
abstract: OBJECTIVE
  Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood.
  
  
  METHODS
  Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300 copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry.
  
  
  RESULTS
  Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2 pg/ml, p=0.003) and the validation (142.2 vs. 89.9 pg/ml, p=0.004) trials. Serum levels of IL-21 (p=0.005) or HBV-DNA (p=0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4(+) and CD8(+) T cells during the first 12 weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations.
  
  
  CONCLUSIONS
  Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Shi-Wu
authors.initials: SW
authors.lastname: Ma
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.forename: Yong-Yin
authors.initials: YY
authors.lastname: Li
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Tang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Jiang
authors.forename: Yue-Xin
authors.initials: YX
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Liu
authors.forename: William G H
authors.initials: WG
authors.lastname: Abbott
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Dong
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Naoumov
authors.forename: Jin-Lin
authors.initials: JL
authors.lastname: Hou
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000097:blood*; D008297:Male; D009705:Nucleosides / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D016896:Treatment Outcome; D000098546:Interleukin-21
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D007378:Interleukins; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D000410:Alanine Transaminase; D000098546:Interleukin-21; D013936:Thymidine