Recent evidence suggests that translocation of bacteria and bacterial products, such as endotoxin from the intestinal lumen into the systemic circulation is a contributing factor in the pathogenesis of chronic liver diseases and the development of complications in cirrhosis. In addition to alterations in the intestinal microbiota and immune system, dysfunction of the intestinal epithelial barrier may be an important factor facilitating bacterial translocation. This review aims to provide an overview of the current evidence of intestinal epithelial barrier dysfunction in human chronic liver diseases and cirrhosis, and to discuss possible contributing factors and mechanisms. Data suggest the presence of intestinal epithelial barrier dysfunction in patients with chronic liver diseases, but are more convincing in patients with cirrhosis, especially in those with complications. The barrier dysfunction can result from both direct and indirect effects of aetiological factors, such as alcohol and obesity, which can cause chronic liver diseases and ultimately cirrhosis. On the other hand characteristics of cirrhosis itself, including portal hypertension, alterations in the intestinal microbiota, inflammation and oxidative stress can affect barrier function of both small and large intestine and may contribute to the development of complications. In conclusion, there are indications for intestinal epithelial barrier dysfunction in patients with chronic liver diseases and especially in patients with cirrhosis, which can be caused by various factors affecting both the small and large intestine.

Early diagnosis of liver cirrhosis may prevent progression and development of complications. Liver biopsy is the current standard, but is invasive and associated with morbidity. We aimed to identify exhaled volatiles within a heterogeneous group of chronic liver disease (CLD) patients that discriminates those with compensated cirrhosis (CIR) from those without cirrhosis, and compare this with serological markers. Breath samples were collected from 87 CLD and 34 CIR patients. Volatiles in exhaled air were measured by gas chromatography mass spectrometry. Discriminant Analysis was performed to identify the optimal panel of serological markers and VOCs for classifying our patients using a random training set of 27 CIR and 27 CLD patients. Two randomly selected independent internal validation sets and permutation test were used to validate the model. 5 serological markers were found to distinguish CIR and CLD patients with a sensitivity of 0.71 and specificity of 0.84. A set of 11 volatiles discriminated CIR from CLD patients with sensitivity of 0.83 and specificity of 0.87. Combining both did not further improve accuracy. A specific exhaled volatile profile can predict the presence of compensated cirrhosis among CLD patients with a higher accuracy than serological markers and can aid in reducing liver biopsies.

Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Increased intestinal permeability has been found in patients with liver cirrhosis, but data on small and large intestine permeability and tight junctions (TJs) in patients with compensated cirrhosis are scarce. We aimed to investigate both small and large intestine permeability in patients with stable compensated cirrhosis compared with healthy controls and evaluated the expression of TJ proteins in mucosal biopsies at duodenal and sigmoid level. Intestinal permeability was assessed in 26 patients with compensated cirrhosis and 27 matched controls using a multisugar test. Duodenal and sigmoid biopsies were available from a subgroup for analyses of gene transcription and expression of key TJ proteins by qRT-PCR and ELISA, respectively. Median 0-5-h urinary sucrose excretion and lactulose/rhamnose ratio were comparable between patients with compensated cirrhosis and controls, whereas 5-24-h urinary sucralose/erythritol ratio was increased in these patients. Downregulation of gene transcription was found for claudin-3 in duodenal biopsies and claudin-4 in sigmoid biopsies, and at the protein level occludin expression was significantly increased in both duodenal and sigmoid biopsies. This study shows that gastroduodenal and small intestine permeability are not altered, whereas large intestine permeability is increased in patients with stable compensated cirrhosis. Only limited alterations were found regarding the expression of TJ proteins in both the small and large intestine.

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As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the 13 C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the 13 C 2 -aminopyrine and the 13 C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the 13 C 2 -aminopyrine breath test in clinical practice.