title: Upregulation of NKG2C+ natural killer cells, TLR-2 expression on monocytes and downregulation of regulatory T-cells influence PEG-IFN treatment efficacy in entecavir-suppressed patients with CHB.
abstract: BACKGROUND
  There is increasing evidence that host immune responses influence antiviral efficacy in chronic hepatitis B (CHB). The aim of this study was to characterize the immunological features responsible for improved treatment responses with pegylated interferon (PEG-IFN)-α2a in entecavir (ETV)-suppressed patients with CHB.
  
  
  METHODS
  Peripheral natural killer (NK) cells, Toll-like receptors (TLRs), T-cell subsets, regulatory T-cells (Tregs) and programmed death 1 (PD-1) were evaluated dynamically in 77 patients undergoing a clinical trial (OSST trial, NCT00940485) by flow cytometry. Response was defined as hepatitis B e antigen (HBeAg) seroconversion, hepatitis B surface antigen (HBsAg) loss and HBsAg seroconversion (either as singular events or in combination at week 48).
  
  
  RESULTS
  Compared with ETV responders or PEG-IFN-α non-responders, PEG-IFN-α responders exhibited a significant decline in HBsAg during treatment (P=0.033 and P<0.001, respectively) and a significant decline in Treg proportions from week 12 to week 24 (P=0.036 and P=0.004, respectively). Moreover, PEG-IFN-α responders showed a significantly higher increase in the NKG2C(+) NK cell proportions from baseline to week 12 (P=0.0073) and of TLR2(+) monocytes at week 12 than PEG-IFN-α non-responders (P=0.039).
  
  
  CONCLUSIONS
  Successful response to PEG-IFN-α correlates with an early significant restoration of impaired immune responses. Although antiviral treatment response can be achieved by both IFN and ETV, the underlying immunological features vary which may explain the generally observed difference in off-treatment durability of response between the two treatments, as well as effects on HBsAg.
authors: Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Weiming
authors: W
authors: Yan
authors: Di
authors: D
authors: Wu
authors: Xiaojing
authors: X
authors: Wang
authors: Tao
authors: T
authors: Chen
authors: Qintao
authors: Q
authors: Lai
authors: Qi
authors: Q
authors: Zheng
authors: Jiaji
authors: J
authors: Jiang
authors: Jinlin
authors: J
authors: Hou
authors: Meifang
authors: M
authors: Han
authors: Qin
authors: Q
authors: Ning
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C100416:peginterferon alfa-2a