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
Open accessAbstract
Background & aims Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation and high mortality. As NSBBs may have beneficial effects on gut motility and permeability and, systemic inflammation, the aims of this prospective, observational study were to determine whether ongoing use of NSBBs reduced 28-day mortality in ACLF patients.Methods The study was performed in 349 patients with ACLF included in the CANONIC study, which is a prospective observational investigation in hospitalized cirrhotic patients with acute deterioration. The data about the use of NSBBs, its type and dosage was specifically recorded. Patient characteristics at enrollment significantly associated with treatment and mortality were taken into account as potential confounders to adjust for treatment effect. A logistic regression model was fitted.Results 164 (47%) ACLF patients received NSBBs whereas 185 patients did not. Although the CLIF-C ACLF scores were similar at presentation, more patients in the NSBB treated group had lower grades of ACLF (p=0.047) at presentation and significantly more patients improved. Forty patients (24.4%) died in NSBB treated group compared with 63 patients (34.1%) (p=0.048) [estimated risk-reduction 0.596 (95%CI: 0.361-0.985; p=0.0436)]. This improvement in survival was associated with a significantly lower white cell count (NSBB: 8.5 (5.8); no NSBB: 10.8 (6.6); p=0.002). No long-term improvement in survival was observed.Conclusions This study shows for the first time that ongoing treatment with NSBBs in cirrhosis is safe and reduces the mortality if they develop ACLF. Careful thought should be given before stopping NSBBs in cirrhotic patients.
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Nonselective β-adrenergic blockers decrease intestinal transit time and reduce intestinal bacterial overgrowth, intestinal permeability and bacterial translocation in experimental cirrhosis and patients.
“Accordingly, nonselective β-adrenergic blockers decrease intestinal transit time and reduce intestinal bacterial overgrowth, intestinal permeability and bacterial translocation in experimental models of cirrhosis as well as in patients153–157.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [155]
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- Authors
- Mookerjee, R. P., Pavesi, M., Thomsen, K. L., Mehta, G., Macnaughtan, J., Bendtsen, F., Coenraad, M., Sperl, J., Gines, P., Moreau, R., Arroyo, V., & Jalan, R.
- Affiliations
- The Royal Free Hospital (GB)
- European Foundation for the Study of Chronic Liver Failure (ES)
- University of Copenhagen (DK)
- Leiden University Medical Center (NL)
- Inserm (FR)
- Corresponding author
- Jalan, Rajiv
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 64
- Issue
- 3
- Pages
- 574-582
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2219970668
- Cited by
- 248
- References
- 30
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 25 · 2023: 27 · 2022: 21 · 2021: 21 · 2020: 22 · 2019: 26 · 2018: 24 · 2017: 33 · 2016: 25 · 2015: 2
- FWCI
- 16.57
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk Fonden (NNF14OC0012141)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- non-selective beta-blockers, acute-on-chronic liver failure, liver cirrhosis, systemic inflammation, 28-day mortality, white blood cell count, CLIF-C ACLF score, intestinal motility, intestinal permeability
- MeSH terms
- Adrenergic beta-Antagonists, Adult, Aged, Female, Humans, Inflammation, Leukocyte Count, Liver Cirrhosis, Male, Middle Aged, Prospective Studies, Logistic Models, Acute-On-Chronic Liver Failure
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