Disaccharides, such as lactulose, are absorbed through the paracellular junction complex, which corresponds to the permeability of larger molecules.13 The L/M (lactulose/mannitol) ratio thus comprises an index to appraise intestinal permeability (IP); this ratio has been reported to be elevated in patients with liver cirrhosis, like those with

Crohn’s disease.13 Elevation of the L/M ratio is marked in end-stage cirrhosis.8,9 Although the results by 51Cr-EDTA, the most frequently used isotope probe, have been conflicting,6,7,11 a recent study by Wnt inhibitor Scarpellini et al.6 showed that impairment of instestinal permeability was significantly associated with Child-Pugh status. Parlesak et al.14 found also that permeability of polyethylene glycol (PEG) with high molecular mass (PEG 1500 and PEG 4000) was increased in patients with alcoholic liver diseases.14 They discussed PEG as an appropriate probe for the assessment of endotoxin translocation on the basis of its homogeneous chemical properties, appropriately adaptable molecular mass and linear, chain-like shape mimicking the structure of endotoxin.14 These demands cannot be met by other commonly used permeability RAD001 nmr marker compounds

described above.15 Lee et al.15 reported that intestinal permeability determined by PEG 400 and 3500 was significantly high in cirrhotics with ascites. In this issue of the Journal of Gastroenterology and Hepatology, Kim et al.16 report that the intestinal permeability index, the percentage of permeability of PEG 3350 to that of PEG 400, was significantly increased on admission for active GI hemorrhage in patients with liver cirrhosis and proven or possible infections. This study is especially interesting on the point that the authors described a strong correlation between the increased

intestinal permeability and the serum level of endotoxin in their discussion, although the precise data were not shown in the text. In this study, the most frequent etiology of liver cirrhosis was alcoholism. There is now accumulating evidence that alcohol misuse in patients with liver disease is associated with increased intestinal permeability and endotoxemia. Thus, significant correlation between the plasma endotoxin levels and intestinal permeability Thymidylate synthase determined by PEG 4000 has been reported in patients with alcoholic liver disease.14 Although the mechanism of increased intestinal permeability in patients with alcoholic cirrhosis is still undetermined, genetic factors and/or environmental factors may be involved. These include the generation of acetaldehyde in the colonic lumen, the status of the intestinal flora,17 nitric oxide and superoxide anion in the intestinal barrier,18 and so on. It is not known if these or other factors especially affect intestinal permeability in patients with liver cirrhosis and gastrointestinal hemorrhage.