门静脉高压症的未来药理学治疗

StephenW

Future Pharmacological Therapies of Portal Hypertension

    Authors
    Authors and affiliations

    Guillermo A. OrtizGuadalupe Garcia-TsaoEmail author

    Guillermo A. Ortiz
        12
    Guadalupe Garcia-Tsao
        12Email author

    1.Section of Digestive DiseasesYale University School of MedicineNew HavenUSA
    2.Digestive Diseases Section, Department of Internal MedicineVA-CT Healthcare SystemWest HavenUSA

Management of Cirrhotic Patient (A Cardenas and P Tandon, Section Editors)
First Online: 19 February 2019

    13 Downloads

Part of the following topical collections:

    Topical Collection on Management of the Cirrhotic Patient

Abstract
Purpose of Review

To provide an overview of recent pharmacological treatments for portal hypertension evaluated in early clinical trials, with particular emphasis on the pathophysiological basis of their use.
Recent Findings

In patients with compensated cirrhosis, even small decreases in portal pressure (as small as 1 mmHg) are associated with a lower probability of decompensation. In patients with decompensated cirrhosis, portal pressure “response” to non-selective beta-blocker (NSBB) therapy is associated with a lower mortality. When present, significant portal hypertension persists even after the elimination of the etiology of cirrhosis and this justifies the continued development of new drugs that target portal hypertension.
Summary

Over several decades, we have gained great depth in the understanding of portal hypertension, its mechanisms and complications. NSBBs, which act by reducing portal venous inflow (an extrahepatic target), are effective in reducing portal pressure and have been the mainstay of therapy for portal hypertension in the last 35 years—being effective in preventing decompensation and variceal hemorrhage. However, because not all patients will have a sufficient response to NSBB and some may be intolerant to NSBB, alternative drugs or drugs that will augment the effect of NSBB on portal pressure are being tested in pre-clinical and early-clinical trials. Many of these drugs target more than one of the intrahepatic or extrahepatic mechanisms implicated in the pathogenesis of portal hypertension in cirrhosis. Out of these proposed therapies, statins have emerged as the most promising new pharmacological therapy for the treatment of portal hypertension.
Keywords
Portal hypertension Liver cirrhosis Hepatic venous pressure gradient Statins Sinusoidal endothelial dysfunction Liver fibrosis Splanchnic vasodilation

StephenW

门静脉高压症的未来药理学治疗

    作者
    作者和附属机构

    Guillermo A. OrtizGuadalupe Garcia-TsaoEmail作者

    吉列尔莫·奥尔蒂斯
        12
    Guadalupe Garcia-Tsao
        12Email作者

    1.消化系疾病大学耶鲁大学医学院新大学
    2.内科医学消化科AV-CT医疗系统West HavenUSA

肝硬化患者的管理（Cardenas和P Tandon，科编辑）
首次在线：2019年2月19日

    13下载

以下主题馆藏的一部分：

    关于肝硬化患者管理的专题收集

抽象
审查目的

概述最近在早期临床试验中评估的门静脉高压药物治疗，特别强调其使用的病理生理学基础。
最近的调查结果

在代偿性肝硬化患者中，即使门静脉压力（小至1 mmHg）的轻微下降也与较低的失代偿可能性相关。在失代偿性肝硬化患者中，门静脉压力对非选择性β受体阻滞剂（NSBB）治疗的“反应”与较低的死亡率相关。当存在时，即使消除了肝硬化的病因，显着的门静脉高压仍然存在，这证明了针对门静脉高压的新药的持续开发是正确的。
摘要

几十年来，我们在了解门静脉高压症，其机制和并发症方面取得了很大的进展。通过减少门静脉流入（肝外靶标）起作用的NSBB在降低门静脉压力方面是有效的，并且在过去35年中已成为门静脉高压症的主要治疗方法 - 有效预防失代偿和静脉曲张出血。然而，由于并非所有患者都对NSBB有足够的反应，而且有些患者可能对NSBB不耐受，因此在临床前和早期临床试验中正在测试增强NSBB对门静脉压力影响的替代药物或药物。这些药物中的许多靶向肝硬化门静脉高压症发病机理中涉及的肝内或肝外机制不止一种。在这些提议的疗法中，他汀类药物已成为治疗门静脉高压症最有希望的新药物疗法。
关键词
门静脉高压肝硬化肝静脉压力梯度他汀类药物正弦内皮功能障碍肝纤维化内脏血管扩张

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