Duodenal gamma‐glutamyltransferase activity in human biopsies: effect of chronic ethanol consumption and duodenal morphology

Seitz, Helmut K.; Velásquez, Douglas A; Waldherr, Rüdiger; Veith, S.; Czygan, P.; Weber, Edgar; Deutsch-Diescher, O. G.; Kommerell, B.

doi:10.1111/j.1365-2362.1985.tb00167.x

Cited by 16 publications

(5 citation statements)

References 38 publications

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“…[19][20][21][22][23] In alcoholic liver disease, villous atrophy is frequently observed; reduction in villous height in relation to crypt depth and lower mucosal surface have been detected by light microscopy in alcoholics, even in the absence of cirrhosis. [24][25][26] Following the introduction of capsule endoscopy, mucosal abnormalities of the small intestine in liver cirrhosis patients with portal hypertension have been well documented and include inflammatory-like abnormalities (oedema, erythema, granularity and friability) as well as vascular lesions (cherry red spots, telangiectasias or angiodysplasia-like lesions and varices). 27 The reduced recovery of mannitol in all our study patients would be consistent with these findings.…”

Section: Discussionmentioning

confidence: 99%

Increased intestinal permeability in malnourished patients with liver cirrhosis

Norman

Pirlich

et al. 2012

Eur J Clin Nutr

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BACKGROUND/OBJECTIVE: Malnutrition is a prominent feature in liver cirrhosis, with deleterious impact on clinical outcome. The objective of this study is to investigate whether malnutrition is associated with increased gastrointestinal permeability in liver cirrhosis reflected by altered urinary excretion of non-metabolizable sugar probes. SUBJECTS/METHODS: Patients with advanced liver cirrhosis (Child Pugh Score B or C) were recruited. Nutritional status was determined according to the Subjective Global Assessment. Intestinal permeability was assessed by measuring the urinary excretion of orally administered, non-metabolized sugar probe molecules. The lactulose/mannitol ratio served as marker for intestinal permeability and reflects non-carrier-mediated transcellular and paracellular transport of the small intestine during the first 5 h. Sucrose recovery in urine within the first 5 h reflects gastroduodenal permeability; sucralose recovery in urine 5-26 h after consumption reflects colonic permeability. RESULTS: Sixty-four patients (56.7±10.8 years; 33% female) were included in the study. Twenty-one patients were considered well nourished according to the Subjective Global Assessment, 23 moderately nourished and 20 patients severely malnourished; 74% had alcoholic liver disease and 67% had cirrhosis stage Child C. Gastroduodenal and colonic permeability was significantly increased in patients with liver cirrhosis compared with 63 healthy controls (0.23±0.22 and 1.37±1.42% vs 0.14±0.10 and 0.41±0.72% in controls), but not different between well and malnourished subjects. Small intestinal permeability (lactulose/ mannitol ratio) was increased in all patients (0.069 ± 0.055%) and further increased in malnourished patients (0.048 ± 0.031% vs 0.084 ± 0.061%, P ¼ 0.004) due to decreased mannitol recovery only. CONCLUSIONS: Gastric, small intestinal and even colonic permeability was altogether increased in liver cirrhosis, and malnutrition was associated with further increased small intestinal permeability indicative of villous atrophy.

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Section: Discussionmentioning

confidence: 99%

Increased intestinal permeability in malnourished patients with liver cirrhosis

Norman

Pirlich

et al. 2012

Eur J Clin Nutr

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“…Conversely, ultrastructural changes of the small intestine mucosa, such as mitochondrial abnormalities, dilatation of endoplasmic reticulum and alteration in the surface of enterocytes, have been reported after chronic alcohol abuse [34,38]. In studies based on morphometric methods a reduced villus height in the jejunal mucosa has been reported in alcoholics [5,43]. A constant finding in recent studies is reduced enterocyte turnover by mitotic inhibition [24,51,52].…”

Section: Introductionmentioning

confidence: 92%

Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic alcohol abusers

et al. 1999

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Excessive consumption of alcoholic beverages may be associated with gastrointestinal symptoms, including dyspepsia and diarrhoea. It is not clear whether or not chronic alcohol ingestion damages the mucosa of the small intestine. We investigated the effect of chronic alcohol abuse on the duodenal mucosa, and particularly on its extracellular matrix (ECM) network. Duodenal biopsy specimens were obtained during upper gastrointestinal endoscopy from 50 chronic alcoholics without cirrhosis and 10 healthy subjects. Morphological studies were performed by routine histology, immunohistochemistry and electron microscopy. Morphometry of duodenal tissues was performed with a computerized image analyser. No significant duodenal epithelial changes were found in alcoholics, despite an evident reduction in the enterocyte turnover. Myofibroblast-like cells were significantly increased in the villus stroma of alcoholics in comparison to controls. These cells stained positively for desmin, alpha-smooth muscle actin and for several ECM components. In alcohol abusers the thickness of the mucosal basement membrane was greater and the staining for collagen I and III was enhanced both in the basement membrane and in the villus stroma. A higher expression of tenascin was also seen at the base of villi of alcoholics. Chronic alcohol abuse may induce fibrosis of duodenal villi which is associated with a transformation of villus juxta-parenchymal cells into active subepithelial myofibroblast-like cells able to produce different ECM components.

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“…This result is presumed partly due to the specific hepatic tissue components analyzed, and contributions from extrahepatic tissues to blood GGT activity (Ikeda and Taniguchi 2005; Whitfield 2001). Still, the contrast between circulating and hepatic GGT activity suggests that serum values with alcohol consumption may reflect enzyme release into circulation in excess of retention in hepatic tissue (Hauge et al 1998; Seitz et al 1985), consistent with the extracellular GGT-mediated catabolism of GSH (Chikhi, et al 1999; Ikeda and Taniguchi 2005). In summary, serum or tissue GGT increases with administration of DME-inducing xenobiotics in humans is now generally considered an adaptive response that is only indirectly linked with DME induction (Zhang et al 2005).…”

Section: Hepatic Metabolic Enzyme Induction and Associated Clinical Pmentioning

confidence: 99%

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

et al. 2010

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Hepatic drug-metabolizing enzyme (DME) induction is an adaptive response associated with changes in preclinical species; this response can include increases in liver weight, hepatocellular hyperplasia and hypertrophy, and upregulated tissue expression of DMEs. Effects of DME induction on clinical pathology markers of hepatobiliary injury and function in animals as well as humans are not well established. This component of a multipart review of the comparative pathology of xenobiotically mediated induction of hepatic metabolizing enzymes reviews pertinent data from retrospective and prospective preclinical and clinical studies. Particular attention is given to studies with confirmation of DME induction and concurrent evaluation of liver and/or serum hepatobiliary marker enzyme activities and histopathology. These results collectively indicate that in the rat, when histologic findings are limited to hepatocellular hypertrophy, DME induction is not expected to be associated with consistent or substantive changes in serum or plasma activity of hepatobiliary marker enzymes such as alanine aminotransferase, alkaline phosphatase, and gamma glutamyltransferase. In the dog and the monkey, published studies also do not demonstrate a consistent relationship across DME-inducing agents and changes in these clinical pathology parameters. However, increased liver alkaline phosphatase or gamma glutamyltransferase activity in dogs treated with phenobarbital or corticosteroids suggests that direct or indirect induction of select hepatobiliary injury markers can occur both in the absence of liver injury and independently of induction of DME activity. Although correlations between tissue and serum levels of these hepatobiliary markers are limited and inconsistent, increases in serum/plasma activities that are substantial or involve changes in other markers generally reflect hepatobiliary insult rather than DME induction. Extrahepatic effects, including disruption of the hypothalamic-pituitary-thyroid axis, can also occur as a direct outcome of hepatic DME induction in humans and animals. Importantly, hepatic DME induction and associated changes in preclinical species are not necessarily predictive of the occurrence, magnitude, or enzyme induction profile in humans.

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Duodenal gamma‐glutamyltransferase activity in human biopsies: effect of chronic ethanol consumption and duodenal morphology

Cited by 16 publications

References 38 publications

Increased intestinal permeability in malnourished patients with liver cirrhosis

Increased intestinal permeability in malnourished patients with liver cirrhosis

Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic alcohol abusers

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

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