Beta-blockers in cirrhosis: Thank you for your attention
Authors: Phillip S. Ge, Bruce A. Runyon
Journal: Journal of Hepatology (2014)

We graciously thank Drs. Ferrarese, Thalheimer, their colleagues, and the editorial board and worldwide readership of the Journal of Hepatology for their interest in our article [[1]Ge P.S. Runyon B.A. The changing role of beta-blocker therapy in patients with cirrhosis.J Hepatol. 2014; 60: 643-653Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar]. We are humbled and honored by the international attention that our article has received, and are excited by the debate that it has ignited within the hepatology community. We have received numerous positive correspondences regarding our review [[2]Zaman A. NEJM Journal Watch. Beta-Blocker Therapy in Cirrhosis: A Paradigm Shift. http://www.jwatch.org/na33999/2014/03/18/beta-blocker-therapy-cirrhosis-paradigm-shift. Accessed April 13, 2014.Google Scholar]. In light of recent studies that have stirred controversy, and in anticipation of future studies that will continue to stir controversy, we believed a fresh objective look at the emerging evidence in the use of beta-blockers in cirrhosis was warranted. At our institution, our chief executive officer frequently impresses his mantra to “put patients first” upon our entire hospital staff [[3]UC Regents. CEO of hospital system has mantra: Put patients first. http://www.today.ucla.edu/portal/ut/PRN-ceo-of-hospital-system-has-mantra-96848.aspx. Accessed April 13, 2014.Google Scholar]. As physicians, we all believe that what comes first is our relentless and selfless service and dedication to our patients. Sometimes, this involves challenging existing treatments when they are later found to be harmful, such as when the same investigator who first studied the benefits of beta-blockers in patients with cirrhosis no longer found these benefits universally applicable [[4]Lebrec D. Poynard T. Hillon P. et al.Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a controlled study.N Engl J Med. 1981; 305: 1371-1374Crossref PubMed Scopus (406) Google Scholar]. We have frequently cared for patients with advanced cirrhosis who were seemingly harmed by beta-blockers once they had fallen outside a certain “therapeutic window” (that had only recently been hypothesized) [[5]Krag A. Wiest R. Albillos A. et al.The window hypothesis: haemodynamic and non-haemodynamic effects of beta-blockers improve survival of patients with cirrhosis during a window in the disease.Gut. 2012; 61: 967-969Crossref PubMed Scopus (135) Google Scholar]. Once their beta-blockers were discontinued, azotemia, hypotension, and acute kidney injury frequently and convincingly resolved. We were certain other clinicians around the world must have encountered similar experiences, yet the scientific evidence appeared to be lacking. How could we turn our back on 30 years of highly cited landmark studies that promoted the use of beta-blockers? Did we miss something that was actually harming our patients? Our article was therefore inspired by a need to re-explore the data. We do not dispute that the benefits of beta-blockers have been well-documented in patients with cirrhosis; however, that was not the focus of our article. We acknowledged these existing benefits and set out to more closely examine the studies that had been ignored [[6]Krag A. Bendtsen F. Henriksen J.H. et al.Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites.Gut. 2010; 59: 105-110Crossref PubMed Scopus (255) Google Scholar], forgotten [[7]Llach J. Gines P. Arroyo V. et al.Prognostic value of arterial pressure, endogenous vasoactive systems, and renal function in cirrhotic patients admitted to the hospital for the treatment of ascites.Gastroenterology. 1988; 94: 482-487Abstract Full Text PDF PubMed Google Scholar], or downplayed [8Serste T. Francoz C. Durand F. et al.Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study.J Hepatol. 2011; 55: 794-799Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar, 9Serste T. Melot C. Francoz C. et al.Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites.Hepatology. 2010; 52: 1017-1022Crossref PubMed Scopus (392) Google Scholar]. What we found was evidence – the quality of which can be debated, but nonetheless evidence stemming from astute clinicians making clinical observations – that beta-blockers were perhaps not as universally indicated as even we ourselves had previously believed. Just as the acetylsalicylic acid of cardiology has its limitations, the “aspirin of hepatology” appears to have its own pitfalls and limitations. Even now, as this debate re-emerges, a new study from Mandorfer and colleagues provides fresh evidence demonstrating the detrimental effect of beta-blocker treatment after the development of spontaneous bacterial peritonitis [[10]Mandorfer M. Bota S. Schwabl P. et al.Non-selective beta blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis.Gastroenterology. 2014; (pii: S0016-5085(14)00306-0, http://dx.doi.org/10.1053/j.gastro.2014.03.005. [Epub ahead of print])PubMed Google Scholar]. More studies and debate are certain to follow. We are extremely pleased that our review has achieved its intended effect of renewing dialogue and reopening the scrutiny on beta-blockers. We hope that this dialogue, along with new research specifically focusing at studying the end-stages of cirrhosis, will continue to be encouraged by the international hepatology community. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Beta-blockers in cirrhosis: Therapeutic window or an aspirin for all?Journal of HepatologyVol. 61Issue 2PreviewWe have read with interest the review article by Ge and Runyon on the changing role of non-selective β-blockers (NSBBs) in cirrhosis [1]. Their role in reduction of portal hypertension is accomplished by lowering portal inflow (β1 blockade) and inducing splanchnic vasoconstriction (β2 blockade). Risk of variceal bleeding correlates also with other factors, i.e., infections and severity of liver dysfunction, suggesting absence of a pure mechanical model. For this reason, patients with more severe disease (Child-Pugh Class C) should undergo primary prophylaxis even in the presence of small varices [2]. Full-Text PDF Open AccessThe changing role of beta-blocker therapy in patients with cirrhosisJournal of HepatologyVol. 60Issue 3PreviewCirrhosis is a leading cause of death in the United States and worldwide. Beta-blockers have been established in numerous studies as part of the cornerstone of the medical management of cirrhosis, particularly in the primary and secondary prevention of variceal hemorrhage. However, new evidence has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites. In this article, we review the beneficial effects of beta-blocker therapy, the potential harms of aggressive beta-blocker therapy, and provide suggestions regarding the appropriate use of this class of medications in patients with cirrhosis. Full-Text PDF Open AccessAn apology for beta blockersJournal of HepatologyVol. 61Issue 2PreviewWe read with interest the recent review on beta-blockers in cirrhosis by Ge and Runyon [1]. This topic is of great importance, as non-selective beta blockers are a pharmacological mainstay in the management of patients with cirrhosis; the amount of evidence has been increasing substantially since the first published trial of their use in the prevention of variceal bleeding [2], particularly in recent years. Full-Text PDF Open Access