背景/目的：全身炎症和对败血症的易感在急性肝衰竭中很常见，从而导致组织损伤和器官衰竭。本文研究在25位急性和亚急性肝衰竭患者中循环中性粒细胞的功能。方法:该实验包括15位急性肝功能衰竭、10位亚急性肝功能衰竭的患者，以及11位健康对照和5位败血症患者。在开始对患者进行重症监护的时候就每隔3-4天检测中性粒细胞，直到死亡、肝移植或者恢复。中性粒细胞表型通过荧光标记的抗CD16和抗CD11b用流式技术检测。中性粒细胞的吞噬能力用FITC标记的变形的大肠杆菌E来测得。活性氧迸发通过检测静息状态的和变形的大肠杆菌E刺激下的中性粒细胞释放的活性氧自由基的百分比获得。并且搜集患者的生理，生化，动脉血氨，微生物指标。用ELISA来检测血清中促炎和抗炎细胞因子。
结果：在急性肝衰竭患者中，与健康对照性比，识别IgG FcγRIII区域的CD16+中性粒细胞的数量明显降低。与健康对照相比，亚急性肝炎患者中的中性粒细胞吞噬能力减弱。在急性和亚急性肝炎中，如果不进行肝移植，中性粒细胞吞噬能力的减弱预示着零生存。在所有组别中中性粒细胞产生的活性氧自由基没有明显增多。结论：在急性和亚急性肝衰竭的循环中性粒细胞的杀菌功能降低，这种现象类似于重症败血症。对于急性肝衰竭，中性粒细胞的功能指数是重要的生物指标，可能预示着器官功能障碍的发展和对败血症的易感程度增高。
BACKGROUND/AIMS: Systemic inflammation and susceptibility to developing sepsis is common in acute liver failure (ALF) resulting in tissue damage and organ failure. This study characterised the function of circulating neutrophils in 25 patients with ALF and sub-acute liver failure (SALF). METHODS: ALF (n=15)/SALF (n=10) patients were prospectively studied and compared with 11 healthy (HC) and 5 septic controls (SC). Neutrophils were isolated on admission to intensive care and every 3-4 days until death/liver transplantation/recovery. Neutrophil phenotype was determined using fluorochrome-labelled antibodies to CD16 and CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) was determined using FITC-labelled opsonised E. coli and oxidative burst (OB) was determined by the percentage of neutrophils producing reactive oxygen species (ROS) at rest, and after stimulation with opsonised E. coli. Physiological variables, biochemistry, arterial ammonia, microbiology and outcomes were collected. Plasma pro- and anti-inflammatory cytokine profiles were performed by ELISA. RESULTS: Neutrophil expression of CD16 which recognises the FcγRIII region of immunoglobulin G was significantly reduced in the ALF cohort (p<0.001) on day 1 compared to HC. NPA was significantly impaired in the SALF cohort compared to HC (p<0.01). Impaired NPA in the ALF and SALF cohorts on admission predicted non-survival without liver transplantation (p=0.01). Spontaneous neutrophil production of ROS was not significantly increased in any of the cohorts. E.coli-stimulated OB was preserved in ALF/SALF cohorts but was significantly impaired in the SC group (p<0.05). CONCLUSION: Circulating neutrophils in ALF/SALF have impaired bacteriocidal function similar to that seen in severe sepsis. Neutrophil function indices are important biomarkers in ALF and may be implicated in the development of organ dysfunction and the increased susceptibility to developing sepsis.
结果：在急性肝衰竭患者中，与健康对照性比，识别IgG FcγRIII区域的CD16+中性粒细胞的数量明显降低。与健康对照相比，亚急性肝炎患者中的中性粒细胞吞噬能力减弱。在急性和亚急性肝炎中，如果不进行肝移植，中性粒细胞吞噬能力的减弱预示着零生存。在所有组别中中性粒细胞产生的活性氧自由基没有明显增多。结论：在急性和亚急性肝衰竭的循环中性粒细胞的杀菌功能降低，这种现象类似于重症败血症。对于急性肝衰竭，中性粒细胞的功能指数是重要的生物指标，可能预示着器官功能障碍的发展和对败血症的易感程度增高。
吉林大学第一医院肝胆胰内科 高修竹 摘译
本文首次发表于[Hepatology 2012 Oct 18.]
本文首次发表于[Hepatology 2012 Oct 18.]
Circulating neutrophil dysfunction in acute liver failure
BACKGROUND/AIMS: Systemic inflammation and susceptibility to developing sepsis is common in acute liver failure (ALF) resulting in tissue damage and organ failure. This study characterised the function of circulating neutrophils in 25 patients with ALF and sub-acute liver failure (SALF). METHODS: ALF (n=15)/SALF (n=10) patients were prospectively studied and compared with 11 healthy (HC) and 5 septic controls (SC). Neutrophils were isolated on admission to intensive care and every 3-4 days until death/liver transplantation/recovery. Neutrophil phenotype was determined using fluorochrome-labelled antibodies to CD16 and CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) was determined using FITC-labelled opsonised E. coli and oxidative burst (OB) was determined by the percentage of neutrophils producing reactive oxygen species (ROS) at rest, and after stimulation with opsonised E. coli. Physiological variables, biochemistry, arterial ammonia, microbiology and outcomes were collected. Plasma pro- and anti-inflammatory cytokine profiles were performed by ELISA. RESULTS: Neutrophil expression of CD16 which recognises the FcγRIII region of immunoglobulin G was significantly reduced in the ALF cohort (p<0.001) on day 1 compared to HC. NPA was significantly impaired in the SALF cohort compared to HC (p<0.01). Impaired NPA in the ALF and SALF cohorts on admission predicted non-survival without liver transplantation (p=0.01). Spontaneous neutrophil production of ROS was not significantly increased in any of the cohorts. E.coli-stimulated OB was preserved in ALF/SALF cohorts but was significantly impaired in the SC group (p<0.05). CONCLUSION: Circulating neutrophils in ALF/SALF have impaired bacteriocidal function similar to that seen in severe sepsis. Neutrophil function indices are important biomarkers in ALF and may be implicated in the development of organ dysfunction and the increased susceptibility to developing sepsis.
