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Compartmentalization and its implication for peripheral immunologically-competent cells to the liver in patients with HBV-related acute-on-chronic liver failure

Authors


  • Zhengsheng Zou and Dongping Xu contributed equally to this work.

  • This work was supported by grants from National Natural Science Foundation of China (No: 30571749), National Grand Program on Key Infectious Disease (No. 2009ZX10004-309 and No. 2008ZX10002-007) and National Key Basic Research Program of China (2001CB51003).

Dr Fu-Sheng Wang, Research Center of Biological Therapy, Beijing Institute of Infectious Diseases, Beijing 302 Hospital, 100 Xi Si Huan Middle Road, Beijing 100039, China. Email: fswang@public.bta.net.cn

Abstract

Aims:  This study attempts to characterize the feature of immunologically competent cells (ICCs) and evaluate its clinical implication in patients with acute-on-chronic liver failure (ACLF) in relation to chronic hepatitis B virus (HBV) infection.

Methods:  Circulating ICCs were examined in ACLF patients (n = 75), as well as in patients with hepatitis B (CHB, n = 31), CHB-related liver cirrhosis (LC, n = 36), and normal controls (NC, n = 30). Intrahepatic ICCs in some patients were further analyzed via immunohistochemical and flow cytometric assays.

Results:  Total lymphocytes, CD4+ T cells, CD8+ T cells, and NK cells in circulation were numerically lower in the ACLF and LC groups compared to the CHB and NC groups. Importantly, the number of these cells was significantly lower in non-surviving ACLF patients compared with surviving ACLF patients. In comparison to NC, ACLF patients displayed a significantly higher ratio of liver-infiltrating CD4+ T-cell frequency than its circulating counterpart, suggesting that the possiblility of the ICCs compartmentalization from the peripheral blood into the liver in ACLF. Immunohistochemical analysis showed that intrahepatic CD4+ cells, CD8+ cells, and CD56+ cells were significantly higher in the ACLF group compared with the other three groups, suggesting a stronger cellular immune response-mediated inflammation in ACLF group than other patient groups.

Conclusions:  The abnormal prevalence of circulating and intrahepatic ICCs possibly acts as an important factor that may drive the progression of HBV-related ACLF.

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