Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy  

作　　者：Juan Zhao Ji-Yuan Zhang Hong-Wei Yu Yu-Lan He Jing-Jing Zhao Juan Li Yue-Ke Zhu Qin-Wei Yao Jin-Huan Wang Hai-Xia Liu Shu-Yun Shi Zheng-Sheng Zou Xiang-Sheng Xu Chun-Bao Zhou Fu-Sheng Wang Qing-Hua Meng 

机构地区：[1]Department of Hepatology,Beijing You An Hospital,Capital Medical University,Beijing,China [2]Research Center for Biological Therapy,The Institute of Translational Hepatology,Beijing 302 Hospital,Beijing,China [3]Department of Infectious Disease,Beijing 302 Hospital,Beijing,China [4]juan Zhao and Ji-Yuan Zhang contributed equally to this work.

出　　处：《Cellular & Molecular Immunology》2012年第5期417-422,共6页中国免疫学杂志（英文版）

基　　金：ACKNOWLEDGEMENTS This study is supported by the National Natural Science Foundation of China （Nos. 30801039 and 81072424） and the major projects of viral hepatitis from Beijing Municipal Science and Technology Commission （No. H020920020890）. We thank the volunteers who generously participated in this study.

摘　　要：Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells （mDCs） and the efficacy of methylprednisolone （MP） treatment for hepatitis B virus （H BV）-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical （CM） management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells （mDCs） and the efficacy of methylprednisolone （MP） treatment for hepatitis B virus （H BV）-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical （CM） management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.

关 键 词：acute-on-chronic liver failure METHYLPREDNISOLONE myeloid dendritic cells plasmacytoid dendritic cells 

分 类 号：TQ467.95[化学工程—制药化工] Q513[生物学—生物化学]