Difficulty in evaluating intestinal permeability in patients with liver cirrhosis: What is the precipitating factor?
Difficulty in evaluating intestinal permeability in patients with liver cirrhosis: What is the precipitating factor?
复制标题
肝硬化患者肠道通透性评估困难：诱发因素是什么？
DOI：
10.1111/j.1872-034x.2012.01104.x
复制
发表时间：
2013
期刊：
影响因子：
4.2
通讯作者：
Fukui H
中科院分区：
文献类型：
--
作者：
藤田尚己;宮地洋英;杉本龍亮;諸岡留美;田中秀明, 長徹二;坂保寛;原田雅典;岩佐元雄;長谷川浩司;竹井謙之;Fukui H
It has been proposed that a “leaky gut” may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in the development of chronic liver injury. 1 There is an ongoing debate involving several authors with regard to the presence and role of increased intestinal permeability in patients with cirrhosis. 2 Some studies have shown an association between hyperpermeability and severity of liver cirrhosis estimated by the Child–Pugh classification, 2–4 but others have failed to reproduce these results. 1, 5, 6 There are certain methodological considerations that should be taken into account when interpreting the conflicting results. 7 Some authors used sugars3, 4, 8 and others used isotope probes, 1, 2, 5, 6 the latter considered to be ideal as they are not subject to synthesis or digestion in the human body. 2 Although the results by 51Cr-ethylenediamine tetraacetic acid, the most frequently used isotope probe, have been conflicting, 1, 2, 6 Scarpellini et al. 2 showed that impairment of intestinal permeability was significantly associated with Child–Pugh status. Parlesak et al. 9 found also that permeability of polyethylene glycol (PEG) with high molecular mass (PEG 1500 and 4000) was increased in patients with alcoholic liver diseases. 9 They discussed whether PEG is 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. 9 Lee et al. 10 reported that intestinal permeability determined by PEG 400 and 3500 was significantly high in cirrhotics with ascites. Kim et al. 11 reported that the intestinal permeability index, the percentage of permeability of PEG 3350 to that of PEG 400, was significantly increased on admission for active gastrointestinal (GI) hemorrhage in patients with liver cirrhosis and proven or possible infections.On the other hand, the assessment of the intestinal permeability by urinary excretion of po administrated unmetabolizable sugars gave us some information on the discrimination between transcellular and paracellular fluxes. 8 Monosaccharides, such as mannitol, are absorbed through the transcellular pathway through the hydrophilic portion of the cell membrane, and reflect the extent of absorption of small molecules. Disaccharides, such as lactulose, are absorbed through the paracellular junction complex, namely, through the tight junctions and extrusion zones of the intervillous spaces, which corresponds to the permeability of larger molecules. 8, 12 Consequently, mannitol absorption as assessed by urinary excretion can be considered as an indicator of the mucosal absorptive area, and lactulose absorption as a measure of the integrity of intestinal mucosal tight junctions. 12, 13 The lactulose/mannitol (L/M) ratio (LMR) thus comprises an index to appraise intestinal permeability and its increase has been traditionally used as a marker of hyperpermeability; 14 this ratio has been reported to be elevated in patients with liver cirrhosis, like those with Crohn’s disease. 8 Among those with liver cirrhosis, elevation of the LMR is marked in the end stage. 3, 4 This increase in intestinal permeability determined by LMR has been reported in several previous studies. 4, 14, 15 Alcoholics with liver disease not only had increased LMR, but they also had marked and statistically significant increases in lactulose excretion. 14 Therefore, the abnormally elevated LMR noted in alcoholics with liver disease is not simply due to a lower level of mannitol excretion but represents increased gut permeability. 14 Pascual et al. 4 found a significantly …
