Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacol. Mar 9, 2016; 5(1): 15-31
Published online Mar 9, 2016. doi: 10.5497/wjp.v5.i1.15
Non-selective beta-blockers in cirrhosis: Current concepts and controversies
Neil Rajoriya, Dhiraj Tripathi
Neil Rajoriya, Dhiraj Tripathi, Department of Hepatology, the New Queen Elizabeth Hospital, Birmingham B15 2TH, United Kingdom
Author contributions: All the authors contributed equally to this manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Dhiraj Tripathi, Consultant Hepatologist, Honorary Senior Lecturer, Department of Hepatology, the New Queen Elizabeth Hospital, Edgbaston, Queen Elizabeth Medical Centre, Birmingham B15 2TH, United Kingdom.
Telephone: +44-121-3714672 Fax: +44-121-6272449
Received: August 28, 2015
Peer-review started: September 1, 2015
First decision: November 24, 2015
Revised: December 11, 2015
Accepted: January 5, 2016
Article in press: January 7, 2016
Published online: March 9, 2016

Non-selective beta-blockers (NSBBs) have been at the forefront in the management of portal hypertension in liver cirrhosis for the last three decades, a trusty component in the armamentarium of the Hepatologist. The role of beta-blockers has been cemented for years in cardiac disease including angina, hypertension and in heart failure, however NSBBs with their non-selective effects on β1 and β2 receptors have led to them fondly being termed “the hepatologist’s aspirin”. NSBBs’ role in reduction of portal pressure in the setting of primary and secondary prophylaxis for variceal haemorrhage has been well established. NSBBs include propranolol, nadolol and carvedilol - with the latter having been shown to be effective in patients who often fail to demonstrate a haemodynamic response to propranolol. Recent observational studies however have served for the Hepatology community to question the beneficial role of NSBBs in portal hypertension, especially in advanced cases with refractory ascites. The deleterious effect in patients with refractory ascites in a few studies led to a U-turn in clinical practice, with some in the Hepatology community withdrawing their usage in patients with advanced cirrhosis. This also led to the “window hypothesis” suggesting there may be only be a finite time frame when NSBBs have a beneficial effect in portal hypertension. The window hypothesis proposed the window for the benefits of NSBBs is closed in early portal hypertension, opening as portal hypertension progresses with it closing in advanced liver disease. The window was proposed to close in conditions such as refractory ascites or spontaneous bacterial peritonitis when patients may not necessarily mount a compensatory haemodynamic response when on NSBBs. Some centres however have continued the practice of NSBBs in advanced cirrhosis with published data challenging the scepticisms of other groups who stop NSBBs. Thus the debate, like the window hypothesis has opened, with more questions to be answered about NSBB’s mechanism of action not only in reducing portal hypertension but also their effects on systemic haemodynamics and on the pro-inflammatory pathways often activated in cirrhosis especially in advanced disease. This article serves to review the role of NSBBs in the management of portal hypertension/cirrhosis and concentrate on current concepts and controversies in this field.

Keywords: Variceal haemorrhage, Non-selective beta-blockers, Portal hypertension, Liver cirrhosis

Core tip: This article serves to discuss the changing role of non-selective beta-blockers in liver disease and portal hypertension. For many years non-selective beta-blockers have been at the forefront in reducing portal hypertensive complications such as variceal haemorrhage, however recent data has questioned their role in advanced liver disease. This article reviews their role in portal hypertension, discusses recent advances in the field and reviews the controversy recently generated regarding their role in advanced liver disease.