Original Article
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World J Gastroenterol. Jul 14, 2013; 19(26): 4146-4154
Published online Jul 14, 2013. doi: 10.3748/wjg.v19.i26.4146
Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure
Ying-Hua Niu, Dong-Lin Yin, Hong-Li Liu, Rui-Tian Yi, Yu-Cong Yang, Hong-An Xue, Tian-Yan Chen, Shu-Lin Zhang, Shu-Mei Lin, Ying-Ren Zhao
Ying-Hua Niu, Hong-Li Liu, Rui-Tian Yi, Tian-Yan Chen, Shu-Lin Zhang, Shu-Mei Lin, Ying-Ren Zhao, Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Dong-Lin Yin, Department of Infectious Diseases, No. 3 People’s Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China
Yu-Cong Yang, Molecular Medicine Center, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Hong-An Xue, Department of Infectious Diseases, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Author contributions: Niu YH and Yin DL carried out all the experiments and analyzed results; Niu YH drafted the manuscript; Yang YC helped to perform flow cytometry; Liu HL helped to edit the manuscript; Yi RT and Zhao YR provided help in data analysis and manuscript preparation; Chen TY, Zhang SL, Xue HA and Lin SM participated in study design and critically reviewed the manuscript; Niu YH and Zhao YR revised the manuscript; all authors read and approved the final manuscript.
Supported by The Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China), No. 2008ZX10002-007, No. 2012ZX10002-007; and the Foundation of Shaanxi Provincial Science and Technology Plan Projects, No. 2011K14-09-09
Correspondence to: Dr. Ying-Ren Zhao, Professor of Medicine, Chief, Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, Shaanxi Province, China. zhaoyingren@sohu.com
Telephone: +86-29-85323634 Fax: +86-29-85323634
Received: January 15, 2013
Revised: May 27, 2013
Accepted: June 1, 2013
Published online: July 14, 2013
Abstract

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multi-organ failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry.

RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ± 0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05).

CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.

Keywords: Hepatitis B virus, Acute-on-chronic liver failure, Regulatory T cells, T helper 17 cells, Treg cell to Th17 cell ratio

Core tip: In this study, the expression of circulating Treg and Th17 cells in hepatitis B virus-related acute-on-chronic liver failure (ACLF), chronic hepatitis B (CHB), and normal controls (NC) was measured using flow cytometric analysis. The percentages of circulating Treg and Th17 cells in ACLF group increased significantly compared with that in CHB group and NC group. Furthermore, the ratio of Treg to Th17 cells increased significantly upon recovery. Our study suggests that the reverting ratio of Treg to Th17 cells at the follow-up phase of ACLF could maintain the immune system at a steady state in favour of good prognosis.