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
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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 作者: StephenW 时间: 2019-4-2 17:50