UCL Institute of Hepatology, Royal Free Campus, London, UK.
Curr Opin Crit Care. 2011 Apr;17(2):170-6. doi: 10.1097/MCC.0b013e328344a076.
During acute-on-chronic liver failure (ACLF), the marked systemic inflammatory response and rapid deterioration in liver function are associated with a significant deterioration in organ perfusion and an appreciable rise in portal pressure. Indeed, the development of sepsis and multiorgan dysfunction that commonly follows presentation in these patients is intricately related to the severity of portal hypertension. It follows that understanding the drivers for rising portal pressure in ACLF will inform new therapies.
As this review aims to highlight, there has been a paradigm shift in understanding of the drivers of portal hypertension, from a prior focus on splanchnic vasodilatation and therapies targeting portal inflow, toward appreciation of increasing intrahepatic resistance as the trigger for further vascular derangement, especially in the context of systemic inflammatory responses.
By elaborating on those mechanisms that are especially perturbed by inflammatory responses, this article aims to show how this understanding has helped inform the identification of potential new targets for therapy in ACLF. Particular emphasis is given to agents with data supporting their progression toward clinical trials and those currently undergoing validation in clinical studies.
在慢加急性肝衰竭（ACLF）中，明显的全身炎症反应和肝功能迅速恶化与器官灌注显著恶化和门静脉压力明显升高有关。事实上，这些患者出现的脓毒症和多器官功能障碍的发展与门静脉高压的严重程度密切相关。因此，了解 ACLF 中门静脉压力升高的驱动因素将为新的治疗方法提供信息。
正如本综述旨在强调的那样，人们对门静脉高压驱动因素的理解已经发生了转变，从以前关注内脏血管舒张和针对门静脉流入的治疗方法，转向认识到肝内阻力增加是进一步血管紊乱的触发因素，特别是在全身炎症反应的情况下。
本文通过详细阐述那些特别受炎症反应干扰的机制，旨在展示这种理解如何有助于确定 ACLF 治疗的潜在新靶点。特别强调了那些有数据支持其进入临床试验进展的药物，以及那些正在临床研究中验证的药物。
