Document Detail


Nonselective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis.
MedLine Citation:
PMID:  23262249     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Evaluation of gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior and after nonselective betablocker (NSBB) treatment. DESIGN: Hepatic venous pressure gradient (HVPG) was measured prior and under NSBB treatment. Gastroduodenal and intestinal permeability were 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: 50 cirrhotics were included (72% male, 18% ascites,60% alcoholic etiology). Abnormal gastroduodenal and intestinal permeability were found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ⩾20mmHg;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 of bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG<20mmHg. 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) was noted with all markers of gastroduodenal/intestinal permeability and with LBP and IL-6 levels. 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. CONCLUSION: 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.
Authors:
T Reiberger; A Ferlitsch; B A Payer; M Mandorfer; B B Heinisch; H Hayden; F Lammert; M Trauner; M Peck-Radosavljevic; H Vogelsang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-19
Journal Detail:
Title:  Journal of hepatology     Volume:  -     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Div. of Gastroenterology & Hepatology, Dept. of Internal Medicine III, Medical University of Vienna, Austria. Electronic address: thomas.reiberger@meduniwien.ac.at.
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