Document Detail

Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis.
MedLine Citation:
PMID:  23262249     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: We evaluated the gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior to and after non-selective betablocker (NSBB) treatment.
METHODS: Hepatic venous pressure gradient (HVPG) was measured prior to and under NSBB treatment. Gastroduodenal and intestinal permeability was assessed by the sucrose-lactulose-mannitol (SLM) test. Anti-gliadin and anti-endomysial antibodies were measured. Levels of LPS-binding protein (LBP) and interleukin-6 (IL-6) were quantified by ELISA, and NOD2 and toll-like receptor 2 (TLR2) polymorphisms were genotyped.
RESULTS: Fifty cirrhotics were included (72% male, 18% ascites, 60% alcoholic etiology). Abnormal gastroduodenal and intestinal permeability was found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ≥20 mm Hg; n=35) had increased markers of gastroduodenal/intestinal permeability (urine sucrose levels p=0.049; sucrose/mannitol ratios p=0.007; intestinal permeability indices p=0.002), and bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG <20 mm Hg. A substantial portion of patients showed elevated levels of anti-gliadin antibodies (IgA: 60%, IgG: 34%) whereas no anti-endomysial antibodies were detected. A significant correlation of portal pressure (i.e., HVPG) with all markers of gastroduodenal/intestinal permeability and with LBP and IL-6 levels was observed. NOD2 and TLR2 risk variants were associated with abnormal intestinal permeability and elevated markers of bacterial translocation. At follow-up HVPG measurements under NSBB, we found an amelioration of gastroduodenal/intestinal permeability and a decrease of bacterial translocation (LBP - 16% p=0.018; IL-6 - 41% p<0.0001) levels, which was not limited to hemodynamic responders. Abnormal SLM test results and higher LBP/IL-6 levels were associated with a higher risk of variceal bleeding during follow-up but not with mortality.
CONCLUSIONS: Abnormal gastroduodenal/intestinal permeability, anti-gliadin antibodies, and bacterial translocation are common findings in cirrhotic patients and are correlated with the degree of portal hypertension. NSBB treatment ameliorates gastroduodenal/intestinal permeability and reduces bacterial translocation partially independent of their hemodynamic effects on portal pressure, which may contribute to a reduced risk of variceal bleeding.
Thomas Reiberger; Arnulf Ferlitsch; Berit A Payer; Mattias Mandorfer; Birgit B Heinisch; Hubert Hayden; Frank Lammert; Michael Trauner; Markus Peck-Radosavljevic; Harald Vogelsang;
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Publication Detail:
Type:  Journal Article     Date:  2012-12-20
Journal Detail:
Title:  Journal of hepatology     Volume:  58     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2014-02-11     Revised Date:  2014-08-01    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  911-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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MeSH Terms
Acute-Phase Proteins
Adrenergic beta-Antagonists / pharmacology*,  therapeutic use*
Bacterial Translocation / drug effects,  physiology
Carrier Proteins / blood*
Cell Membrane Permeability / drug effects*,  physiology
Follow-Up Studies
Hemodynamics / drug effects,  physiology
Hypertension, Portal / drug therapy,  epidemiology,  metabolism
Interleukin-6 / blood*
Intestinal Absorption / drug effects*,  physiology
Kaplan-Meier Estimate
Lactulose / metabolism
Liver Cirrhosis / drug therapy*,  epidemiology,  metabolism*
Mannitol / metabolism
Membrane Glycoproteins / blood*
Middle Aged
Sucrose / metabolism
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Adrenergic beta-Antagonists; 0/Carrier Proteins; 0/Interleukin-6; 0/Membrane Glycoproteins; 0/lipopolysaccharide-binding protein; 3OWL53L36A/Mannitol; 4618-18-2/Lactulose; 57-50-1/Sucrose
Comment In:
Aliment Pharmacol Ther. 2013 Sep;38(6):652   [PMID:  23964732 ]
Aliment Pharmacol Ther. 2013 Sep;38(6):653   [PMID:  23964733 ]
Gastroenterology. 2014 Jul;147(1):247-9   [PMID:  24866430 ]

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