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Volume 48, Number 2, April 2015

Increased CD4+CD25+ regulatory T cells correlate with poor short-term outcomes in hepatitis B virus-related acute-on-chronic liver failure patients 

Chuan Shen, Wen-Zhao Yan, Cai-Yan Zhao, Hong-Hao Che, Xiao-Yu Liu, Zhen-Zhong Liu, Ya-Dong Wang, Wei Wang, Meng Li, Jian Gao

Received: March 10, 2013    Revised: October 15, 2013    Accepted: October 31, 2013   


Corresponding author:

Cai-Yan Zhao
Corresponding author. Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang 050051, China. 


Background and purpose: 

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). 



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. 



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. 



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. 


Key words:

Chronic hepatitis B, Forkhead-winged helix transcription factor, Immune response, Liver failure, Regulatory T cell