Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Campus, London NW3 2PF, United Kingdom.
Laboratory of Experimental Gastroenterology, ULB, Brussels, Belgium; Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, ULB, Brussels, Belgium.
J Hepatol. 2014 Jul;61(1):155-63. doi: 10.1016/j.jhep.2014.03.014. Epub 2014 Mar 18.
Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation, and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic process, regulated by complex interactions between the injured hepatocyte, the sinusoidal endothelial cell, the Kupffer cell and the hepatic stellate cell, which impact on sinusoidal calibre. Recent findings suggest these haemodynamic findings are most marked in patients with superimposed inflammation. The precise mechanisms for vascular dysfunction in cirrhosis with superimposed inflammation remain to be fully elucidated but several studies over the past decade have started to generate the hypothesis that inflammation may be a key mediator of the pathogenesis and severity of portal hypertension in this context. This review provides a comprehensive overview of the biological mechanisms for inflammation playing a key role in the severity of portal hypertension, and illustrates potential novel therapies that act by modifying these processes.
门静脉高压症传统上被认为是一个进行性的过程，涉及包括纤维化、结节形成和血管血栓形成在内的超微结构变化，导致肝内血流阻力增加。然而，人们越来越认识到，这种血管阻力的一个重要组成部分来自于一个动态过程，它受受损肝细胞、窦内皮细胞、库普弗细胞和肝星状细胞之间复杂相互作用的调节，从而影响窦状隙的口径。最近的发现表明，这些血液动力学发现在伴有炎症的患者中最为明显。在伴有炎症的肝硬化中血管功能障碍的确切机制仍有待充分阐明，但过去十年的几项研究开始提出这样的假设，即炎症可能是门静脉高压发病机制和严重程度的关键介质。这篇综述全面概述了炎症在门静脉高压严重程度中发挥关键作用的生物学机制，并说明了通过改变这些过程起作用的潜在新疗法。
