Intestinal permeability in cirrhotic patients with and without ascites

Abstract

Malnutrition is a common finding in patients with liver cirrhosis. Malnutrition has been shown to be associated with increased morbidity and mortality. Its pathogenesis remains unclear but both poor dietary intake and increased energy expenditure have been reported.Spontaneous bacterial peritonitis is an important clinical problem in cirrhotics. It may occur as a consequence of repeated access of bacteria from the intestinal lumen (translocation) to the mesenteric lymph nodes. One of the mechanisms proposed to explain bacterial translocation in cirrhosis includes increased intestinal permeability.The aims of the present study were to evaluate GI symptoms in cirrhotic patients and their possible relation to nutritional status, to assess whether gastric sensorimotor dysfunction or metabolic disturbances are associated with reduced food intake, and to investigate the role of ascites in intestinal permeability in patients with liver cirrhosis.Gastrointestinal symptoms and health-related quality of life (HRQOL) were assessed with the aid of two questionnaires. Gastric sensorimotor function was measured by means of an electronic barostat. Food intake, as assessed with a food diary, was related to fasting and postprandial glucose, insulin, leptin, and ghrelin concentrations. Intestinal permeability was evaluated by a 51 Cr-EDTA permeability test. Cirrhotics were found to have increased severity of GI symptoms compared with reference values from the general population. A relationship between GI symptoms and compromised HRQOL as well as weight loss was observed.Proximal stomach relaxation to a meal was increased in patients with liver cirrhosis as compared with healthy controls but the relation between gastric accommodation and energy intake was found to be disturbed in these patients. Gastric sensitivity to distension was shown to be related to GI symptom severity and to liver cirrhosis severity scores.Patients with liver cirrhosis exhibited higher postprandial insulin and glucose concentrations compared to controls. Cirrhotics had higher fasting leptin that fell significantly postmeal and they showed an attenuated increase of ghrelin before the next expected meal. Altered glucose and hormonal levels in patients with cirrhosis were associated with poor food intake.Only a few patients with cirrhosis had increased intestinal permeability, as assessed by a 51 Cr-EDTA test, which was not influenced to a major extent by ascites. Conclusions: In patients with liver cirrhosis GI symptom severity is high and it is associated with impaired HRQOL and weight loss. Gastric accommodation is not involved in the poor food intake observed in cirrhotics and gastric sensitivity seems to be a relevant factor for GI symptom generation in these patients. Altered postprandial glucose, leptin, and ghrelin levels are correlated to reduced energy intake in this patient group. Increased intestinal permeability is probably of limited importance in the pathophysiology of bacterial infections in patients with liver cirrhosis and ascites.

Changes of Intestinal Functions in Liver Cirrhosis

“…Some authors have shown an association between increased intestinal permeability and severity of liver cirrhosis as assessed by the Child-Pugh classification [68,69,70], but others have failed to reproduce these results [71,72,73]. Increased permeability on hospital admission has also been related to some complications of liver cirrhosis [67], although the published studies are not always unanimous [74].…”

Increased intestinal macromolecular permeability and urine nitrite excretion associated with liver cirrhosis with ascites

“…The concept of altered intestinal per meability is important and has been implicated in a number of pathological situations, including celiac disease associated with antigen permeability, allergic intestinal diseases such as digestive hypersensitivity, inflammatory diseases such as Crohn's disease, ulcerative colitis, acute pancreatitis, alcoholic liver disease and LC associated with substance permeability during inflammation [5,21,22] . The pathogenic mechanisms implicated in the failure of intestinal barrier in cirrhosis have not been fully elucidated as yet and remains to be investigated.…”

“…Distribution of PEG in ascites might have caused a lower urinary excretion rate and thus underestimated possible permeability changes in patients with ascites. However, Kalaitzakis et al assessing intestinal permeability with 51Cr-EDTA concluded that a loss of 51Cr-EDTA into the ascitic compartment was unlikely and paracentesis had no significant effect on the urinary 51Cr-EDTA excretion, which suggests that ascites in itself does not unduly affect the test results [5] . In the present study, ascitic fluid from three cirrhotic patients was tested for PEG and it was not detected; therefore, the possibility of lower urinary excretion rates due to distribution of PEG in ascites can be ruled out.…”

“…Intestinal permeability in LC 3885 in the pathogenesis of chronic liver injury and as contributory factors in the development of dangerous complications, such as encephalopathy and bacterial infections in LC [4] . However, other investigators have suggested that intestinal permeability is probably of limited importance in the pathophysiology of bacterial infections in patients with LC [5] . Intestinal permeability in LC has been reported as being increased or normal [6][7][8][9][10] .…”

Spontaneous Bacterial Peritonitis: Is It Still A Life-Threatening Issue in Cirrhosis?

“…One of the factors that lead to loss of the intestinal barrier function is the structural damage of the intestinal wall with increasing permeability of bacteria into systemic circulation, especially in advanced stages of liver disease that is already associated with altered bacterial flora [35,36] . Portal hypertension induces enteropathy with intestinal wall thickening, capillary dilatation, edema of the lamina propria and reduction of villus/crypt ratio that can influence bacterial translocation [37] .…”