Department of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China.
Cell Mol Immunol. 2012 Sep;9(5):417-22. doi: 10.1038/cmi.2011.51. Epub 2012 Jan 9.
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 (HBV)-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at 10-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.
急性肝衰竭(ACLF)是一种严重的生命威胁并发症。肝移植是唯一可行的治疗选择;然而,由于多种限制,它在患者中的应用受到了限制。皮质类固醇作为 ACLF 的可选治疗方法已引起广泛关注。其使用的基本原理是免疫系统在启动和持续肝损伤中可能发挥作用。为了评估髓样树突状细胞(mDC)与甲基强的松龙(MP)治疗乙型肝炎病毒(HBV)相关 ACLF 患者疗效之间的关系,我们招募了 30 名接受 MP 治疗的 HBV 相关 ACLF 患者,每隔 10 天进行一次;26 名患者接受保守的医学(CM)管理作为对照。与健康受试者相比,这些 ACLF 患者的 DC 亚群功能较低。此外,与幸存者相比,死亡/移植患者在两组中的功能性 mDC 较低。此外,基线时 mDC 数量减少与 ACLF 患者的高死亡率相关。重要的是,MP 治疗可显著降低 28 天死亡率,并且所有 MP 患者在 MP 治疗的 10 天内均表现出循环 mDC 数量的快速初始下降。随后,MP 幸存者表现出 mDC 数量的持续增加,同时总胆红素水平下降超过 30%。然而,MP 死亡/移植患者与幸存者相比缺乏这些连续反应。这些证据强烈表明,基线时 mDC 数量较高以及治疗结束时 mDC 数量的恢复可能是 ACLF 患者对皮质类固醇治疗反应良好的预后标志物。