Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.
Liver Int. 2013 Apr;33(4):633-41. doi: 10.1111/liv.12051. Epub 2013 Jan 29.
Manipulation of the liver during liver surgery results in profound hepatocellular damage. Experimental data show that mobilization-induced hepatocellular damage is related to hepatic inflammation. To date, information on this link in humans is lacking. As it is possible to modulate inflammation, it is clinically relevant to unravel this relationship.
This observational study aimed to establish the association between liver mobilization and hepatic inflammation in humans.
Consecutive patients requiring mobilization of the right hemi-liver during liver surgery were studied. Plasma samples and liver biopsies were collected prior to and directly after mobilization and after transection of the liver. Hepatocellular damage was assayed by liver fatty acid-binding protein (L-FABP) and aminotransferase levels. Hepatic inflammation was determined by (a) immunohistochemical identification of myeloperoxidase (MPO) and CD68- positive cells and (b) hepatic gene expression of inflammatory and cell adhesion molecules (IL-1β, IL-6, IL-8, VCAM-1 and ICAM-1).
A total of 25 patients were included. L-FABP levels increased significantly during mobilization (301 ± 94 ng/ml to 1599 ± 362 ng/ml, P = 0.008), as did ALAT levels (36 ± 5 IU/L to 167 ± 21 IU/L, P < 0.001). A significant increase in MPO (P = 0.001) and CD68 (P = 0.002) positive cells was noticed in the liver after mobilization. The number of MPO-positive cells correlated with the duration of mobilization (Pearson correlation=0.505, P = 0.033). Hepatic gene expression of pro-inflammatory cytokines IL-1β and IL-6, chemo-attractant IL-8 and adhesion molecule ICAM-1 increased significantly during liver manipulation.
Liver mobilization is associated with hepatocellular damage and liver inflammation, as shown by infiltration of inflammatory cells and upregulation of genes involved in acute inflammation.
在肝外科手术中,肝脏的操作会导致明显的肝细胞损伤。实验数据表明,动员引起的肝细胞损伤与肝炎症有关。迄今为止,人类对此联系的信息尚不清楚。由于可以调节炎症,因此阐明这种关系在临床上具有重要意义。
本观察性研究旨在确定人类肝脏动员与肝炎症之间的关联。
连续研究了在肝外科手术中需要动员右半肝的患者。在动员前、动员后直接以及肝横断后采集血浆样本和肝活检。通过肝脂肪酸结合蛋白(L-FABP)和转氨酶水平测定肝细胞损伤。通过(a)髓过氧化物酶(MPO)和 CD68 阳性细胞的免疫组织化学鉴定和(b)炎症和细胞黏附分子(IL-1β、IL-6、IL-8、VCAM-1 和 ICAM-1)的肝基因表达来确定肝炎症。
共纳入 25 例患者。动员过程中 L-FABP 水平显著升高(301±94ng/ml 至 1599±362ng/ml,P=0.008),丙氨酸氨基转移酶(ALAT)水平也显著升高(36±5IU/L 至 167±21IU/L,P<0.001)。动员后肝脏中 MPO(P=0.001)和 CD68(P=0.002)阳性细胞明显增加。MPO 阳性细胞的数量与动员持续时间相关(Pearson 相关系数=0.505,P=0.033)。肝动员过程中促炎细胞因子 IL-1β 和 IL-6、趋化因子 IL-8 和黏附分子 ICAM-1 的肝基因表达显著增加。
肝动员与肝细胞损伤和肝炎症有关,表现为炎症细胞浸润和参与急性炎症的基因上调。