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      β-blockers in advanced cirrhosis: More friend than enemy

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          Abstract

          Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a “therapeutic window” has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.

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          Most cited references77

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          EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis

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            Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension.

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              Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.

              Patients with cirrhosis hospitalized for an acute decompensation (AD) and organ failure are at risk for imminent death and considered to have acute-on-chronic liver failure (ACLF). However, there are no established diagnostic criteria for ACLF, so little is known about its development and progression. We aimed to identify diagnostic criteria of ACLF and describe the development of this syndrome in European patients with AD. We collected data from 1343 hospitalized patients with cirrhosis and AD from February to September 2011 at 29 liver units in 8 European countries. We used the organ failure and mortality data to define ACLF grades, assess mortality, and identify differences between ACLF and AD. We established diagnostic criteria for ACLF based on analyses of patients with organ failure (defined by the chronic liver failure-sequential organ failure assessment [CLIF-SOFA] score) and high 28-day mortality rate (>15%). Of the patients assessed, 303 had ACLF when the study began, 112 developed ACLF, and 928 did not have ACLF. The 28-day mortality rate among patients who had ACLF when the study began was 33.9%, among those who developed ACLF was 29.7%, and among those who did not have ACLF was 1.9%. Patients with ACLF were younger and more frequently alcoholic, had more associated bacterial infections, and had higher numbers of leukocytes and higher plasma levels of C-reactive protein than patients without ACLF (P < .001). Higher CLIF-SOFA scores and leukocyte counts were independent predictors of mortality in patients with ACLF. In patients without a prior history of AD, ACLF was unexpectedly characterized by higher numbers of organ failures, leukocyte count, and mortality compared with ACLF in patients with a prior history of AD. We analyzed data from patients with cirrhosis and AD to establish diagnostic criteria for ACLF and showed that it is distinct from AD, based not only on the presence of organ failure(s) and high mortality rate but also on age, precipitating events, and systemic inflammation. ACLF mortality is associated with loss of organ function and high leukocyte counts. ACLF is especially severe in patients with no prior history of AD. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Clin Mol Hepatol
                Clin Mol Hepatol
                CMH
                Clinical and Molecular Hepatology
                The Korean Association for the Study of the Liver
                2287-2728
                2287-285X
                July 2021
                3 December 2020
                : 27
                : 3
                : 425-436
                Affiliations
                Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
                Author notes
                Corresponding author : Samuel S. Lee Liver Unit, University of Calgary Cumming School of Medicine, 3330 Hospital Dr NW, Calgary, AB T2N 4N1, Canada Tel: +1-403 220 8457, Fax: +1-403 592 5090 E-mail: samlee@ 123456ucalgary.ca

                Editor: Yeon Seok Seo, Korea University College of Medicine, Korea

                [*]

                These authors contributed equally to the manuscript as first author.

                [†]

                Current address: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Pusan National University College of Medicine and Liver center, Pusan National University Yangsan Hospital, Yangsan, Korea

                Author information
                http://orcid.org/0000-0003-4431-272X
                Article
                cmh-2020-0234
                10.3350/cmh.2020.0234
                8273637
                33317244
                87eec8bf-0b6d-4429-9353-093835d20203
                Copyright © 2021 by The Korean Association for the Study of the Liver

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 August 2020
                : 10 November 2020
                : 18 November 2020
                Categories
                Review

                Gastroenterology & Hepatology
                cirrhosis,portal hypertension,varices,refractory ascites
                Gastroenterology & Hepatology
                cirrhosis, portal hypertension, varices, refractory ascites

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