Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis

作者：Reiberger Thomas^*; Ferlitsch Arnulf; Payer Berit A; Mandorfer Mattias; Heinisch Birgit B; Hayden Hubert; Lammert Frank; Trauner Michael; Peck Radosavljevic Markus; Vogelsang Harald

来源：Journal of Hepatology, 2013, 58(5): 911-921.

DOI：10.1016/j.jhep.2012.12.011

• Hepatic venous pressure gradient
• HVPG
• Gastroduodenal permeability
• Intestinal permeability
• Bacterial translocation
• Antigliadin antibodies
• NOD2
• TLR2

Background %26 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. %26lt;br%26gt;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. %26lt;br%26gt;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 %26gt;= 20 mmHg; 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 %26lt;20 mmHg. 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 %26lt;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. %26lt;br%26gt;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.

• 出版日期2013-5