Skip to main content
SpringerLink
Log in

Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites

  • Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking.

Aims

To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites.

Methods

Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan–Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence.

Results

Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71–1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45–1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47–1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48–3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2–32.1%).

Conclusions

Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. de Franchis R, Abraldes JG, Bajaj J, et al. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63:743–752.

    Article  PubMed  Google Scholar 

  2. Merli M, Lucidi C, Di Gregorio V, et al. The chronic use of beta-blockers and proton pump inhibitors may affect the rate of bacterial infections in cirrhosis. Liver Int. 2015;35:362–369.

    Article  PubMed  Google Scholar 

  3. Reiberger T, Ferlitsch A, Payer BA, et al. Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis. J Hepatol. 2013;58:911–921.

    Article  PubMed  CAS  Google Scholar 

  4. Mookerjee RP, Pavesi M, Thomsen KL, et al. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure. J Hepatol. 2016;64:574–582.

    Article  PubMed  CAS  Google Scholar 

  5. Sersté 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;55:794–799.

    Article  PubMed  CAS  Google Scholar 

  6. Mandorfer M, Bota S, Schwabl P, et al. Nonselective b blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014;146:1680–1690.

    Article  PubMed  CAS  Google Scholar 

  7. Bossen L, Krag A, Vilstrup H, et al. Non-selective β-blockers do not affect mortality in cirrhosis patients with ascites: post hoc analysis of three RCTs with 1198 patients. Hepatology. 2015 Nov 24. https://doi.org/10.1002/hep.28352. [Epub ahead of print].

  8. Bhutta AQ, Garcia-Tsao G, Reddy KR, et al. Beta-blockers in hospitalised patients with cirrhosis and ascites: mortality and factors determining discontinuation and reinitiation. Aliment Pharmacol Ther. 2018;47:78–85.

    Article  PubMed  CAS  Google Scholar 

  9. Chirapongsathorn S, Valentin N, Alahdab F, et al. Nonselective β-blockers and survival in patients with cirrhosis and ascites: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2016;14:1096–1104.

    Article  PubMed  CAS  Google Scholar 

  10. Krag A, Wiest R, Albillos A, et al. The window hypothesis: haemodynamic and non-haemodynamic effects of betablockers improve survival of patients with cirrhosis during a window in the disease. Gut. 2012;61:967–969.

    Article  PubMed  CAS  Google Scholar 

  11. Facciorusso A, Chandar AK, Murad MH, et al. Comparative efficacy of pharmacological strategies for management of type 1 hepatorenal syndrome: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2017;2:94–102.

    Article  PubMed  Google Scholar 

  12. Ge PS, Runyon BA. Treatment of patients with cirrhosis. N Engl J Med. 2016;375:767–777.

    Article  PubMed  CAS  Google Scholar 

  13. Ge PS, Runyon BA. The changing role of beta-blocker therapy in patients with cirrhosis. J Hepatol. 2014;60:643–653.

    Article  PubMed  CAS  Google Scholar 

  14. Ge PS, Runyon BA. When should the β-blocker window in cirrhosis close? Gastroenterology. 2014;146:1597–1599.

    Article  PubMed  Google Scholar 

  15. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Accessed on November 30, 2017.

  16. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–269.

    Article  PubMed  Google Scholar 

  17. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wells GA, Shea B, O’Connell D, et al. The Newcastle—Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed on November 30, 2017.

  19. Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.

    Article  PubMed  PubMed Central  Google Scholar 

  20. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.

    Article  PubMed  CAS  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Facciorusso A, Di Maso M, Muscatiello N. Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma: a meta-analysis. Dig Liver Dis. 2016;48:571–577.

    Article  PubMed  CAS  Google Scholar 

  23. http://cran.r-project.org/web/packages/metafor/index.html. Accessed on November 2017.

  24. Escorsell A, Bañares R, García-Pagán JC, et al. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial. Hepatology. 2002;35:385–392.

    Article  PubMed  Google Scholar 

  25. Lo GH, Chen WC, Chen MH, et al. Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis. Gastrointest Endosc. 2004;59:333–338.

    Article  PubMed  Google Scholar 

  26. Shah HA, Azam Z, Rauf J, et al. Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial. J Hepatol. 2014;60:757–764.

    Article  PubMed  CAS  Google Scholar 

  27. Borroni G, Salerno F, Cazzaniga M, et al. Nadolol is superior to isosorbide mononitrate for the prevention of the first variceal bleeding in cirrhotic patients with ascites. J Hepatol. 2002;37:315–321.

    Article  PubMed  CAS  Google Scholar 

  28. Cholongitas E, Papatheodoridis GV, Manesis EK, et al. Spontaneous bacterial peritonitis in cirrhotic patients: is prophylactic propranolol therapy beneficial? J Gastroenterol Hepatol. 2006;21:581–587.

    Article  PubMed  CAS  Google Scholar 

  29. Sersté T, Melot C, Francoz C, et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010;52:1017–1022.

    Article  PubMed  CAS  Google Scholar 

  30. Robins AE, Bowden A, Watson W, et al. Propanolol at modest dose does not impair survival in patients with cirrhosis and refractory ascites. Gut. 2012;61:A183.

    Article  Google Scholar 

  31. Mazhar K, ElliotT AC, Rockey DC. The beneficial effect of beta-blockers in patients with cirrhosis, portal hypertension, and ascites. Hepatology. 2013;58:S945.

    Google Scholar 

  32. Leithead JA, Rajoriya N, Tehami N, et al. Non-selective β-blockers are associated with improved survival in patients with ascites listed for liver transplantation. Gut.. 2015;64:1111–1119.

    Article  PubMed  CAS  Google Scholar 

  33. Kimer N, Feineis M, Møller S, Bendtsen F. Beta-blockers in cirrhosis and refractory ascites: a retrospective cohort study and review of the literature. Scand J Gastroenterol. 2015;50:129–137.

    Article  PubMed  CAS  Google Scholar 

  34. Aday AW, Mayo MJ, Elliott A, Rockey DC. The beneficial effect of beta-blockers in patients with cirrhosis, portal hypertension and ascites. Am J Med Sci. 2016;351:169–176.

    Article  PubMed  Google Scholar 

  35. Bang UC, Benfield T, Hyldstrup L, et al. Effect of propranolol on survival in patients with decompensated cirrhosis: a nationwide study based Danish patient registers. Liver Int. 2016;36:1304–1312.

    Article  PubMed  CAS  Google Scholar 

  36. Sinha R, Lockman KA, Mallawaarachchi N, et al. Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites. J Hepatol.. 2017;67:40–46.

    Article  PubMed  CAS  Google Scholar 

  37. Garcia-Pagan JC. Portal hypertension: nonselective [beta]- blockers in patients with refractory ascites. Nat Rev Gastroenterol Hepatol. 2011;8:10–11.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastroenterology Unit, Department of Medical Sciences, University of Foggia, AOU Ospedali Riuniti, Viale Pinto, 1, 71100, Foggia, Italy

    Antonio Facciorusso & Nicola Muscatiello

  2. Belhoul Speciality Hospital, Dubai, United Arab Emirates

    Sunil Roy

  3. Athens Medical School, Evgenideio Hospital, Athens, Greece

    Sarantis Livadas

  4. College Green, Kingston, Jamaica

    Adwalia Fevrier-Paul

  5. Uganda Research Unit on AIDS, Entebbe, Uganda

    Clara Wekesa

  6. Pamukkale University, Denizli, Turkey

    Ismail Dogu Kilic

  7. Bl Kapoor Superspeciality Hospital, New Delhi, India

    Amit Kumar Chaurasia

  8. National Institute of Hygiene, Rabat, Morocco

    Mina Sadeq

Authors
  1. Antonio Facciorusso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sunil Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarantis Livadas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adwalia Fevrier-Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clara Wekesa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ismail Dogu Kilic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amit Kumar Chaurasia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mina Sadeq
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nicola Muscatiello
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors have contributed to and agreed on the content of the manuscript. AF wrote the article and performed the statistical analysis. AF, SR, SL, AFP, CW, IDK, AKC, MS performed the literature search and collected the data. NM revised the draft.

Corresponding author

Correspondence to Antonio Facciorusso.

Ethics declarations

Conflict of interest

None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 145 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Facciorusso, A., Roy, S., Livadas, S. et al. Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites. Dig Dis Sci 63, 1737–1746 (2018). https://doi.org/10.1007/s10620-018-5092-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-018-5092-6

Keywords

Search

Navigation