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Impact of non-selective ß-blockers on hepatic encephalopathy in patients with liver cirrhosis

  • Author Footnotes
    1 both authors contributed equally
    Christian Labenz
    Footnotes
    1 both authors contributed equally
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Author Footnotes
    1 both authors contributed equally
    Michael Nagel
    Footnotes
    1 both authors contributed equally
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Gerrit Toenges
    Affiliations
    Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Robert Kuchen
    Affiliations
    Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Jörn M. Schattenberg
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Max Hilscher
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Yvonne Huber
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Jens U. Marquardt
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Joachim Labenz
    Affiliations
    Department of Internal Medicine, Diakonie Klinikum, Jung-Stilling Hospital, Siegen, Germany
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  • Peter R. Galle
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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  • Marcus-Alexander Wörns
    Correspondence
    Corresponding author at: Department of Internal Medicine I / Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55101 Mainz, Germany.
    Affiliations
    Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
    Search for articles by this author
  • Author Footnotes
    1 both authors contributed equally
Published:August 29, 2020DOI:https://doi.org/10.1016/j.ejim.2020.08.022

      Highlights

      • Non-selective beta-blockers (NSBB) are the backbone for the treatment of portal hypertension in patients with liver cirrhosis.
      • Relevant side effects of NSBB may occur in patients with more impaired liver function.
      • NSBB use seems to be associated with the presence of covert hepatic encephalopathy.
      • NSBB use seems to increase the incidence of overt hepatic encephalopathy in patients with decompensated cirrhosis.

      Abstract

      Background

      Non-selective β-blockers (NSBB) are frequently used for the treatment of portal hypertension and gastroesophageal varices in patients with liver cirrhosis; however prospective studies investigating the potential association between NSBB use and hepatic encephalopathy (HE) are still scarce. We investigated the potential association between NSBB use and the presence of covert HE (CHE) as well as the development of overt HE (OHE).

      Methods

      224 patients with liver cirrhosis were included into this cohort study at two German centers and followed for a median of 364 days. CHE was diagnosed by pathological results in the PHES. Predictors for the presence of CHE or the development of OHE were analyzed using logistic-regression or cox-regression models.

      Results

      39% of patients were treated with NSBB and CHE was detected in 34% of patients at study inclusion. In logistic regression analysis, NSBB use, higher MELD score and a history of OHE were independently associated with the presence of CHE. Cumulative incidence of OHE was considerably higher in NSBB users than in non-users (p<0.001). In Cox-regression models NSBB use, presence of CHE, lower albumin and higher MELD score were independently associated with the development of OHE in the whole cohort as well as in the subgroup of patients with decompensated liver cirrhosis. NSBB use was independently associated with higher risk of mortality or need for liver transplantation in decompensated patients but not in the total cohort.

      Conclusion

      NSBB use seems to be associated with the presence of CHE as well as the development of OHE in patients with decompensated liver cirrhosis.

      Keywords

      Abbreviations:

      HE (hepatic encephalopathy), MHE (minimal hepatic encephalopathy), CHE (covert hepatic encephalopathy), HVPG (hepatic venous pressure gradient), HE1 (hepatic encephalopathy grade 1), PHES (Portosystemic Hepatic Encephalopathy Score), MELD (model of end stage liver disease), NAFLD (non-alcoholic fatty liver disease), NSBB (non-selective β-blocker(s))
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