Pharmacological management of portal hypertension: current status and future.
Pharmacological management of portal hypertension: current status and future.
复制标题
DOI：
10.1097/cm9.0000000000001004
复制
发表时间：
2020-10-05
影响因子：
6.1
通讯作者：
Ding HG
中科院分区：
文献类型：
--
作者：
Gao ZQ;Han Y;Li L;Ding HG
门静脉高压症(PHT)是肝硬变严重并发症的诱因，包括食道胃底静脉曲张出血(EVB)、腹水、肝性脑病、肝硬化性心肌病、急性肾损伤和肝肾综合征(AKI-HRS)，可导致死亡或增加肝移植的需要。到目前为止，评估门静脉压力(PP)和门静脉高压(PHT)的最广泛接受的方法是通过经颈-肝静脉球囊插管测量肝静脉压力梯度(HVPG)。[3]PHT的药物治疗旨在减少门静脉压力和预防PHT相关的并发症。[4，5]鉴于门静脉压力是由门静脉血流和肝血管阻力决定的，[4]目前使用的药物主要针对调节增加的肝脏血流，如减少高动力循环、肾素-血管紧张素-醛固酮系统激活、血管增生和侧支循环形成，或减少血管内阻力，如抑制肝纤维化、再生结节、在PHT的情况下，动脉血管扩张同时发生在内脏和体循环中，因此，激活神经体液和血管收缩系统，导致钠和水保留，增加血容量，增加心输出量。[7]特利加压素、生长抑素(SMT)或奥曲肽和非选择性b-受体阻滞剂(NSBB)通过内脏血管收缩减少门静脉流入。然而，血管活性物质和收缩细胞之间的串扰往往导致肝脏微循环异常和PHT的发生。[6]这些可能是未来PHT药物治疗的新靶点。
Portal hypertension (PHT) is the trigger of the severe complications of cirrhosis, including esophagogastric variceal bleeding (EVB), ascites, hepatic encephalopathy, cirrhotic cardiomyopathy, acute kidney injury and hepatorenal syndrome (AKI-HRS), which may cause death or increase the need for liver transplantation.[1, 2] Of these, EVB remains one of the deadliest complications of PHT. As of now, the most widely accepted measure to assess portal pressure (PP) and PHT is the hepatic venous pressure gradient (HVPG) via transjugular-hepatic vein balloon catheterization.[3] The pharmacological management of PHT aims to reduce PP and prevent PHT-related complications.[4, 5] Given that PP is determined by portal blood flow and hepatic vascular resistance,[4] currently used drugs are mainly targeted to modulate the increased liver blood flow, such as reducing hyperdynamic circulation, renin-angiotensin-aldosterone system activation, vascular hyperplasia, and collateral circulation formation, or decrease intravascular resistance, such as inhibiting liver fibrosis, regenerative nodules, and angiogenesis.[6] In the setting of PHT, arterial vasodilation occurs both in the splanchnic and systemic circulation, therefore, activates the neurohumoral and vasoconstrictive systems, which leads to sodium and water retention, increased blood volume, and increased cardiac output.[7] Terlipressin, somatostatin (SMT) or octreotide, and non-selective b-blockers (NSBBs) decrease the portal venous inflow through splanchnic vasoconstriction. However, the crosstalk between vasoactive substances and contractile cells often leads to abnormal liver microcirculation and PHT development.[6] Those may be new targets for the pharmacological management of PHT in the future.