title: Increased CD4+CD25+ regulatory T cells correlate with poor short-term outcomes in hepatitis B virus-related acute-on-chronic liver failure patients.
abstract: BACKGROUND
  The roles of CD4(+)CD25(+) regulatory T cells (Treg) in chronicity of hepatitis B virus (HBV) infection have been confirmed. We aimed to explore alteration of Treg in patients with HBV-related acute-on-chronic liver failure (ACLF).
  
  
  METHODS
  Thirty-two HBV-related ACLF patients, 44 chronic hepatitis B patients, and 41 healthy controls were recruited. We detected frequencies of peripheral Treg and intrahepatic forkhead winged helix transcription factor (Foxp3)(+) cells. Inhibitory activity of Treg was assessed by functional suppression assays. Serum interferon-γ and interleukin-10 were also determined.
  
  
  RESULTS
  Peripheral Treg and intrahepatic Foxp3(+) cells were more markedly increased in ACLF than chronic hepatitis B and controls (all p < 0.001), and the Foxp3(+) cells located predominantly in the portal areas. The Treg frequency was positively correlated with HBV DNA load, international normalized ratio, model of end stage liver disease score, and serum interleukin-10 level in ACLF patients. Functional assays in vitro demonstrated that ACLF patients exhibited higher suppressive effects of Treg on proliferations of autologous CD4(+)CD25(-) T cells than controls. On logistic regression, prolonged international normalized ratio and higher peripheral Treg frequency predicted 30-day survival of ACLF.
  
  
  CONCLUSIONS
  The patients with HBV-related ACLF exhibit increased amounts of Treg, of which redistribution from periphery to liver seems to modulate liver inflammation. Higher Treg amounts are associated with more severe liver disease in ACLF, and its level in combination with international normalized ratio may assist prediction of short-term outcomes of HBV-related ACLF.
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Wen-Zhao
authors.initials: WZ
authors.lastname: Yan
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: zhaocy2005@163.com.
authors.forename: Cai-Yan
authors.initials: CY
authors.lastname: Zhao
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Che
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Liu
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Wang
authors.affiliation: Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000473:pathology*; D000328:Adult; D015704:CD4 Antigens / Q000032:analysis*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Chronic hepatitis B; Forkhead-winged helix transcription factor; Immune response; Liver failure; Regulatory T cell