Yang Runkuan, Zou Xiaoping, Tenhunen Jyrki, Tønnessen Tor Inge
Department of Intensive Care Medicine, Tampere University Hospital, University of Tampere, 10 Bio Katu, 33014 Tampere, Finland.
Department of Critical Care Medicine, University of Pittsburgh Medical School, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Mediators Inflamm. 2017;2017:5928078. doi: 10.1155/2017/5928078. Epub 2017 Jun 13.
Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.
急性肝衰竭（ALF）是多种原因导致严重肝细胞损伤的最终结果。当肝细胞死亡程度超过肝脏再生能力时，就会发生急性肝衰竭。急性肝衰竭死亡率高，与多器官功能衰竭（MOF）和脓毒症相关；然而，其潜在机制仍不清楚。新出现的证据表明，急性肝衰竭患者/动物循环中的高迁移率族蛋白B1（HMGB1）浓度很高，它可导致多器官损伤并介导肠道细菌移位（BT）。肠道细菌移位引发/诱导全身炎症反应综合征（SIRS），进而可导致急性肝衰竭患者发生多器官功能衰竭。在实验性急性致命性肝损伤中，阻断高迁移率族蛋白B1可显著减少肠道细菌移位并改善肝细胞再生。因此，高迁移率族蛋白B1似乎是急性肝衰竭中连接肠道细菌移位和全身炎症的一个重要因素。急性肝衰竭患者/动物循环中的组蛋白水平也很高，这可能是急性肝衰竭患者全身炎症的主要介质。细胞外组蛋白可杀死内皮细胞并引发免疫刺激作用，从而导致多器官损伤。中和组蛋白可减轻急性肝、肺和脑损伤。总之，高迁移率族蛋白B1和组蛋白在急性肝衰竭中诱导全身炎症和多器官功能衰竭方面发挥着重要作用。
