Bile acid metabolism in cirrhosis

Schwartz, Charles C.; Almond, Hilton R.; Vlahčevič, Z. Reno; Swell, Leon

doi:10.1016/0016-5085(79)90154-9

Cited by 29 publications

(3 citation statements)

References 26 publications

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“…Moreover, the fact that already 3 days after BDL in absence of liver fibrosis/cirrhosis mucus thickness is reduced and numbers of goblet cells are decreased supports a role of bile salts for goblet cell homeostasis. In conjunction, with the well-known deficiency in luminal availability of bile/acids 24 and associated reduction in ileal FXR-signalling in cirrhotic rodents 15 , it is tempting to speculate that deficient bile-acid induced FXR-signalling could mediate this phenotype. However, we were unable to detect FXR-expression in goblet cells suggesting a paracrine mode of action for bile/acids which needs to be delineated in further studies.…”

Section: Discussionmentioning

confidence: 99%

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Intestinal mucus and gut-vascular barrier: FxR-modulated entry sites for pathological bacterial translocation in liver cirrhosis

Sorribas

Jakob

Yılmaz

et al. 2019

Preprint

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Background and aimsPathological bacterial translocation (PBT) in liver cirrhosis (LC) is the hallmark for spontaneous bacterial infections increasing mortality several-fold. Factors known to contribute to PBT in LC are among others an increased intestinal permeability of which however, the mucus layer has not been addressed so far in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined but we hypothesize that the recently described gut vascular barrier (GVB) is impaired in experimental portal hypertension leading to increased accessibility of the vascular compartment for translocating bacteria.ResultsHealthy and pre-hepatic portal-hypertensive (PPVL) mice lack translocation of FITC-dextran and GFP-Escherichia coli from the small intestine to the liver whereas bile-duct-ligated (BDL) and CCl4-induced cirrhotic mice demonstrate pathological translocation which is not altered by prior thoracic-duct ligation. Mucus layer is reduced in thickness with loss of goblet-cells and Muc2-staining and expression in cirrhotic but not PPVL-mice associated with bacterial overgrowth in inner mucus layer and pathological translocation of GFP-E.coli through the ileal epithelium. GVB is profoundly altered in BDL and CCl4-mice with Ileal extravasation of large-sized 150 kDa-FITC-dextran but only minor in PPVL-mice. This pathological endothelial permeability and accessibility in cirrhotic mice associates with an augmented expression of PV1 in intestinal vessels. OCA but not fexaramine stabilizes the GVB whereas both FXR-agonists ameliorate gut-liver-translocation of GFP-E.coli.ConclusionsLiver cirrhosis but not portal hypertension per se grossly impairs the endothelial and muco-epithelial barriers promoting PBT to the portal-venous circulation. Both barriers appear FXR-modulated with –agonists reducing PBT via the portal-venous route.

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Section: Discussionmentioning

confidence: 99%

“…Liver cirrhosis is characterized by deficient levels of luminal bile acids in the gut 24 . Bile acids have been long known for their major effects on the microbiome and the intestinal barrier function.…”

Section: Introductionmentioning

confidence: 99%

Intestinal mucus and gut-vascular barrier: FxR-modulated entry sites for pathological bacterial translocation in liver cirrhosis

Sorribas

Jakob

Yılmaz

et al. 2019

Preprint

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“…Increased hemolysis in cirrhosis patients lead to increased concentration of unconjugated bilirubin and bilirubin monoconjugates in bile which are more easily deconjugated by either non-enzymatic hydrolysis or β-glucuronidase secreted by hepatocytes and biliary epithelialcells 27,46 . There is marked reduction of bile acid pools in cirrhosis patients due to impaired synthesis and reduced secretion of phospholipids especially cholesterol in bile [47][48][49] . Combined effect of all these patho-physiological factors will enhance the risk of pigment stone formation in cirrhosis patients.…”

Section: Pigment Stonesmentioning

confidence: 99%

Gallstone Disease in Cirrhosis—Pathogenesis and Management

Mallick

Anand

2022

Journal of Clinical and Experimental Hepatology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Noninvasive Measurement of Nutrient Portal Blood Shunting: An Experimental Study with [14C]Ursodeoxyeholie Acid

et al. 2007

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All of the methods proposed for measuring portal blood flow are either invasive, estimate total rather than nutrient flow, and none has proved reliable in cirrhotic patients. A method has been derived from pharmacokinetic principles used for the calculation of bioavailability of drugs according to the route of administration (i.v. or p.o.) and tested experimentally in 20 pigs. A tracer dose of [14C]ursodeoxycholic acid, a biliary acid with a high‐liver first‐pass effect, is administered in the duodenum, and serial peripheral blood samples are taken. Later, the same dose of the same drug is administered i.v. The shunt fraction of portal blood F is obtained by the ratio of the areas under the plasma level vs. time curves (“AUC”) after p.o. and i.v. administrations: The pigs were divided into three experimental groups, (i) Group I: undisturbed portal flow; (ii) Group II: total diversion of portal blood with an end‐to‐side portacaval shunt, and (iii) Group HI: partial diversion of portal blood through a side‐to‐side portacaval shunt. Portal flow was measured during surgery with an electromagnetic flowmeter above and below the shunt and the degree of shunting calculated. Results show that the shunt fraction measured with ursodeoxycholic acid is well‐correlated with hemodynamic data. No overlap between Groups I to III is observed. It is concluded that the shunt fraction of nutrient portal blood can be measured with this noninvasive method. Minute amounts of ursodeoxycholic acid were used in order to be completely metabolized by the liver, even in spite of hepatocellular dysfunction. Therefore, this method should be valid in cirrhotic patients and be useful to decide the type of portosystemic shunt to propose for the decompression of gastroesophageal varices.

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Bile acid metabolism in cirrhosis

Cited by 29 publications

References 26 publications

Intestinal mucus and gut-vascular barrier: FxR-modulated entry sites for pathological bacterial translocation in liver cirrhosis

Intestinal mucus and gut-vascular barrier: FxR-modulated entry sites for pathological bacterial translocation in liver cirrhosis

Gallstone Disease in Cirrhosis—Pathogenesis and Management

Noninvasive Measurement of Nutrient Portal Blood Shunting: An Experimental Study with [14C]Ursodeoxyeholie Acid

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