Abstract:
BACKGROUND:Increased intestinal permeability in cirrhosis exerts a pivotal role in the pathogenesis of spontaneous bacterial peritonitis and other complications of cirrhosis through promotion of systemic endotoxemia. This study was designed to investigate whether the expression of tight junction (TJ) proteins, which regulate gut paracellular permeability, is altered in the intestinal mucosa of patients with liver cirrhosis and study its potential association with the stage of liver disease and the development of systemic endotoxemia. DESIGN:Twenty-four patients with cirrhosis at a decompensated (n = 12, group A) or compensated condition (n = 12, group B) and 12 healthy controls (group C) were subjected to duodenal biopsy. The expression of the TJ proteins occludin and claudin-1 in the intestinal epithelium was evaluated by immunohistochemistry. Plasma endotoxin concentrations were also determined. RESULTS:Patients with cirrhosis presented significantly higher serum endotoxin concentrations as compared to healthy controls (P < 0·001), whilst endotoxemia was higher in decompensated disease (P < 0·05 vs. compensated cirrhosis). Patients with decompensated and compensated cirrhosis presented significantly reduced expression of occludin and claudin-1 as compared to controls (P < 0·01, respectively). These alterations were significantly more pronounced in decompensated patients as compared to compensated (P < 0·05). Regarding occludin, in patients with cirrhosis, a specific pattern of expression in the intestinal epithelium was observed, with a gradually increasing loss of expression from crypt to tip of the villi. Occludin and claudin-1 expression were inversely correlated with Child-Pugh score (P < 0·001), the grade of oesophageal varices (P < 0·01) and endotoxin concentrations (P < 0·001). CONCLUSIONS:This study demonstrates for the first time that human liver cirrhosis induces significant alterations in enterocytes' TJs. These changes might represent an important cellular mechanism for intestinal barrier dysfunction and hyperpermeability in patients with liver cirrhosis.
journal_name
Eur J Clin Investjournal_title
European journal of clinical investigationauthors
Assimakopoulos SF,Tsamandas AC,Tsiaoussis GI,Karatza E,Triantos C,Vagianos CE,Spiliopoulou I,Kaltezioti V,Charonis A,Nikolopoulou VN,Scopa CD,Thomopoulos KCdoi
10.1111/j.1365-2362.2011.02609.xsubject
Has Abstractpub_date
2012-04-01 00:00:00pages
439-46issue
4eissn
0014-2972issn
1365-2362journal_volume
42pub_type
杂志文章abstract:BACKGROUND:High levels of circulating cell-free DNA (cfDNA) have been reported in patients with inflammatory conditions. The aim of the study was to investigate the levels of cfDNA in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS:Comparative groups comprised 22 nonpregnant and 36 pregnant wom...
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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