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      Beta-blockers in cirrhosis: Evidence-based indications and limitations

      review-article
      Author(s): 1 , 1 , 1 , ∗
      Publication date (Electronic):
      Journal: JHEP Reports
      Publisher: Elsevier
      Keywords: NSBBs, ACLF, ascites, cirrhosis, spontaneous bacterial peritonitis, portal hypertension, varices, ACLF, acute-on-chronic liver failure, AKI, acute kidney injury, ALD, alcohol-related liver disease, ARD, absolute risk difference, AV, atrioventricular, EBL, endoscopic band ligation, GOV, gastroesophageal varices, HRS, hepatorenal syndrome, HVPG, hepatic venous pressure gradient, IGV, isolated gastric varices, IRR, incidence rate ratio, ISMN, isosorbide mononitrate, MAP, mean arterial pressure, NASH, non-alcoholic steatohepatitis, NNH, number needed to harm, NNT, number needed to treat, NR, not reported, NSBBs, non-selective beta-blockers, OR, odds ratio, PH, portal hypertension, PHG, portal hypertensive gastropathy, RCT, randomised controlled trials, RR, risk ratio, SBP, spontaneous bacterial peritonitis, SCL, sclerotherapy, TIPS, transjugular intrahepatic portosystemic shunt

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          Summary

          Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding. Recent evidence indicates that NSBBs could prevent liver decompensation in patients with compensated cirrhosis. Despite solid data favouring NSBB use in cirrhosis, some studies have highlighted relevant safety issues in patients with end-stage liver disease, particularly with refractory ascites and infection. This review summarises the evidence supporting current recommendations and restrictions of NSBB use in patients with cirrhosis.

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          Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.

          S. K. Sarin, D Lahoti, S P Saxena … (1992)
          To determine the prevalence and natural history of gastric varices, we prospectively studied 568 patients (393 bleeders and 175 nonbleeders) with portal hypertension (cirrhosis in 301 patients, noncirrhotic portal fibrosis in 115 patients, extrahepatic portal vein obstruction in 117 patients and hepatic venous outflow obstruction in 35 patients). Primary (present at initial examination) gastric varices were seen in 114 (20%) patients; more were present in bleeders than in non-bleeders (27% vs. 4%, respectively; p < 0.001). Secondary (occurring after obliteration of esophageal varices) gastric varices developed in 33 (9%) patients during follow-up of 24.6 +/- 5.3 mo. Gastric varices (compared with esophageal varices) bled in significantly fewer patients (25% vs. 64%, respectively). Gastric varices had a lower bleeding risk factor than did esophageal varices (2.0 +/- 0.5 vs. 4.3 +/- 0.4, respectively) but bled more severely (4.8 +/- 0.6 vs. 2.9 +/- 0.3 transfusion units per patient, respectively). Once a varix bled, mortality was more likely (45%) in gastric varix patients. Gastric varices were classified as gastroesophageal or isolated gastric varices. Type 1 gastroesophageal varices (lesser curve varices) were the most common (75%). After obliteration of esophageal varices, type 1 gastroesophageal varices disappeared in 59% of patients and persisted in the remainder; bleeding from persistent gastroesophageal varices was more common than it was from gastroesophageal varices that were obliterated (28% vs. 2%, respectively; p < 0.001). Type 2 gastroesophageal varices, which extend to greater curvature, bled often (55%) and were associated with high mortality. Type 1 isolated gastric varices patients had only fundal varices, with a high (78%) incidence of bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)
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            Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.

            Àngels Escorsell, D. Grace, Antonio J. Pagán … (2005)
            Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage. Their effectiveness in preventing varices is unknown. We randomly assigned 213 patients with cirrhosis and portal hypertension (minimal hepatic venous pressure gradient [HVPG] of 6 mm Hg) to receive timolol, a nonselective beta-blocker (108 patients), or placebo (105 patients). The primary end point was the development of gastroesophageal varices or variceal hemorrhage. Endoscopy and HVPG measurements were repeated yearly. During a median follow-up of 54.9 months, the rate of the primary end point did not differ significantly between the timolol group and the placebo group (39 percent and 40 percent, respectively; P=0.89), nor were there significant differences in the rates of ascites, encephalopathy, liver transplantation, or death. Serious adverse events were more common among patients in the timolol group than among those in the placebo group (18 percent vs. 6 percent, P=0.006). Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year. Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events. (ClinicalTrials.gov number, NCT00006398.) Copyright 2005 Massachusetts Medical Society.
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              β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial

              Càndid Villanueva, Agustin Albillos, Joan Genescà … (2019)
              Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) ≥10 mm Hg, is the strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with β blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH.
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                Author and article information

                Contributors
                Jaime Bosch
                Journal
                Journal ID (nlm-ta): JHEP Rep
                Journal ID (iso-abbrev): JHEP Rep
                Title: JHEP Reports
                Publisher: Elsevier
                ISSN (Electronic): 2589-5559
                Publication date PMC-release: 20 December 2019
                Publication date Collection: February 2020
                Publication date (Electronic): 20 December 2019
                Volume: 2
                Issue: 1
                Electronic Location Identifier: 100063
                Affiliations
                [1 ]Swiss Liver Center, UVCM, Inselspital, Bern University Hospital, Department of Biomedical Research, University of Bern, Bern, Switzerland
                Author notes
                [∗ ]Corresponding author. Address: Swiss Liver Center, UVCM, Inselspital, Bern University Hospital, Department of Biomedical Research, University of Bern, Bern, Switzerland. jaume.bosch@ 123456idibaps.org
                Article
                Publisher ID: S2589-5559(19)30157-0 Publisher ID: 100063
                DOI: 10.1016/j.jhepr.2019.12.001
                PMC ID: 7005550
                PubMed ID: 32039404
                SO-VID: 380fed4c-58ad-4304-b4e0-379f8bd7cd0a
                Copyright © © 2020 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 25 October 2019
                Date revision received : 29 November 2019
                Date accepted : 3 December 2019
                Categories
                Subject: Review

                Keywords: nsbbs,aclf,ascites,cirrhosis,spontaneous bacterial peritonitis,portal hypertension,varices,aclf, acute-on-chronic liver failure,aki, acute kidney injury,ald, alcohol-related liver disease,ard, absolute risk difference,av, atrioventricular,ebl, endoscopic band ligation,gov, gastroesophageal varices,hrs, hepatorenal syndrome,hvpg, hepatic venous pressure gradient,igv, isolated gastric varices,irr, incidence rate ratio,ismn, isosorbide mononitrate,map, mean arterial pressure,nash, non-alcoholic steatohepatitis,nnh, number needed to harm,nnt, number needed to treat,nr, not reported,nsbbs, non-selective beta-blockers,or, odds ratio,ph, portal hypertension,phg, portal hypertensive gastropathy,rct, randomised controlled trials,rr, risk ratio,sbp, spontaneous bacterial peritonitis,scl, sclerotherapy,tips, transjugular intrahepatic portosystemic shunt
                Data availability:
                Keywords: nsbbs, aclf, ascites, cirrhosis, spontaneous bacterial peritonitis, portal hypertension, varices, aclf, acute-on-chronic liver failure, aki, acute kidney injury, ald, alcohol-related liver disease, ard, absolute risk difference, av, atrioventricular, ebl, endoscopic band ligation, gov, gastroesophageal varices, hrs, hepatorenal syndrome, hvpg, hepatic venous pressure gradient, igv, isolated gastric varices, irr, incidence rate ratio, ismn, isosorbide mononitrate, map, mean arterial pressure, nash, non-alcoholic steatohepatitis, nnh, number needed to harm, nnt, number needed to treat, nr, not reported, nsbbs, non-selective beta-blockers, or, odds ratio, ph, portal hypertension, phg, portal hypertensive gastropathy, rct, randomised controlled trials, rr, risk ratio, sbp, spontaneous bacterial peritonitis, scl, sclerotherapy, tips, transjugular intrahepatic portosystemic shunt

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