Department of Surgery, School of Medicine, Complutense University of Madrid, Madrid, Spain.
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; INEUROPA (Instituto de Neurociencias del Principado de Asturias), Oviedo, Spain.
Arch Med Res. 2019 Jul;50(5):271-284. doi: 10.1016/j.arcmed.2019.09.002. Epub 2019 Oct 5.
Chronic inflammatory liver disease with an acute deterioration of liver function is named acute-on-chronic inflammation and could be regulated by the metabolic impairments related to the liver dysfunction. In this way, the experimental cholestasis model is excellent for studying metabolism in both types of inflammatory responses. Along the evolution of this model, the rats develop biliary fibrosis and an acute-on-chronic decompensation. The acute decompensation of the liver disease is associated with encephalopathy, ascites, acute renal failure, an acute phase response and a splanchnic increase of pro- and anti-inflammatory cytokines. This multiorgan inflammatory dysfunction is mainly associated with a splanchnic and systemic metabolic switch with dedifferentiation of the epithelial, endothelial and mesothelial splanchnic barriers. Furthermore, a splanchnic infiltration by mast cells occurs, which suggests that these cells could carry out a compensatory metabolic role, especially through the modulation of hepatic and extrahepatic mitochondrial-peroxisome crosstalk. For this reason, we propose the hypothesis that mastocytosis in the acute-on-chronic hepatic insufficiency could represent the development of a survival metabolic mechanisms that mitigates the noxious effect of the hepatic functional deficit. A better understanding the pathophysiological response of the mast cells in liver insufficiency and portal hypertension would help to find new pathways for decreasing the high morbidity and mortality rate of these patients.
慢性炎症性肝病伴肝功能急性恶化称为慢加急性肝损伤，其可能与肝功能障碍相关的代谢紊乱有关。通过这种方式，实验性胆汁淤积模型非常适合研究两种炎症反应中的代谢变化。随着该模型的发展，大鼠会发生胆汁淤积性纤维化和慢加急性失代偿。肝疾病的急性失代偿与肝性脑病、腹水、急性肾衰竭、急性时相反应和内脏促炎和抗炎细胞因子增加有关。这种多器官炎症性功能障碍主要与内脏和全身代谢转换有关，上皮、内皮和间皮内脏屏障去分化。此外，肥大细胞发生内脏浸润，这表明这些细胞可能发挥代偿性代谢作用，尤其是通过调节肝内和肝外的线粒体-过氧化物酶体串扰。因此，我们提出假说，即慢性肝功能不全中的肥大细胞增多症可能代表一种生存代谢机制的发展，减轻肝功能缺陷的有害影响。更好地理解肥大细胞在肝功能不全和门静脉高压中的病理生理反应，将有助于找到降低这些患者高发病率和死亡率的新途径。
