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

J Hepatol. 2013 May;58(5):911-21. doi: 10.1016/j.jhep.2012.12.011. Epub 2012 Dec 20.


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.

MeSH terms

  • Acute-Phase Proteins
  • Adrenergic beta-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Bacterial Translocation / drug effects
  • Bacterial Translocation / physiology
  • Carrier Proteins / blood*
  • Cell Membrane Permeability / drug effects*
  • Cell Membrane Permeability / physiology
  • Comorbidity
  • Female
  • Follow-Up Studies
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Hypertension, Portal / drug therapy
  • Hypertension, Portal / epidemiology
  • Hypertension, Portal / metabolism
  • Interleukin-6 / blood*
  • Intestinal Absorption / drug effects*
  • Intestinal Absorption / physiology
  • Kaplan-Meier Estimate
  • Lactulose / metabolism
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / metabolism*
  • Male
  • Mannitol / metabolism
  • Membrane Glycoproteins / blood*
  • Middle Aged
  • Sucrose / metabolism


  • Acute-Phase Proteins
  • Adrenergic beta-Antagonists
  • Carrier Proteins
  • Interleukin-6
  • Membrane Glycoproteins
  • lipopolysaccharide-binding protein
  • Mannitol
  • Lactulose
  • Sucrose