title: [Relationship between the changes in immune cells and HBeAg loss following antiviral treatment in chronic hepatitis B patients].
abstract: OBJECTIVE
  To observe the changes in hepatitis B virus (HBV)-specific and non-specific cellular immunity that accompany viral load decline during adefovir dipivoxil (ADV) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, and to explore the antiviral immunity mechanism underlying the treatment response.
  
  
  METHODS
  Serial analysis of cellular immunological parameters was performed in HBeAg-positive patients (n = 20) throughout the 48-week course of ADV therapy (10 mg/d). HBV-specific T cell reactivity to HBV core antigen (HBcAg) was assessed by enzyme-linked immunosorbent spot assay and cell proliferation assay at pre-treatment (baseline) and post-treatment weeks 4, 12, 24, 36, and 48. Percentage of regulatory T cells (Tregs), as well as activated peripheral natural killer (NK) cells (expressing the NKG2D receptor), was measured by flow cytometry. Comparisons of means were performed by the two-tailed t-test or the Mann-Whitney rank sum test.
  
  
  RESULTS
  After 48 weeks of ADV therapy, HBeAg loss was observed in six of the 20 (30%) patients and 14 patients remained HBeAg-positive. In the patients with HBeAg loss, the viral load reduction was accompanied by a significantly enhanced response rate of HBV-specific interferon (IFN)-gamma-producing CD4+ T cells [measured as (spot forming cells/peripheral blood mononuclear cells); baseline: (661.25+/-281.97) *10(-6) vs. week 48: (280.75+/-104.33) *10(-6), P = 0.045]. In contrast, patients without HBeAg loss showed no significant differences in T cell response rates. The patient groups with and without HBeAg loss showed similar proportions of peripheral blood Tregs during the treatment course, which included a trend of gradual decrease from baseline to week 4 with steady levels thereafter. In addition, both groups showed a similar increase in NKG2D expression that began at week 12 and peaked at week 48.
  
  
  CONCLUSIONS
  HBV-specific T cell reactivity temporally increases in some ADV-treated chronic hepatitis B patients, and this trend is strongly associated with HBeAg loss. Furthermore, recovery of HBV-specific T cell reactivity promotes viral clearance and HBeAg seroconversion.
authors.affiliation: Center of Liver Diseases, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Yue-yong
authors.initials: YY
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Yu-rui
authors.initials: YR
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.forename: Da-wu
authors.initials: DW
authors.lastname: Zeng
authors.forename: Su
authors.initials: S
authors.lastname: Lin
authors.forename: Jia-ji
authors.initials: JJ
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K