<b>Kinetics of primary bile acids in patients after orthotopic liver transplantation</b>

Sauer, Peter; Rudolph, G; Endele, R.; Senn, Martin; Theilmann, L; Otto, Gerd; Stremmel, Wolfgang; Stiehl, A.

doi:10.1046/j.1365-2362.1996.2290581.x

Cited by 9 publications

(14 citation statements)

References 22 publications

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“…To the best of our knowledge, this is the first study to demonstrate that CsA inhibits bile salt synthesis in pediatric liver transplant patients. Although it has been long known that CsA interacts with bile formation in humans, i.e., cholelithiasis and cholestasis have repeatedly been reported in patients on CsA therapy,36 data on bile salt synthesis and pool size in humans chronically treated with CsA are scarce 37. Our observation that CsA reduces bile salt synthesis is in agreement with in vitro and in vivo animal data.…”

Section: Discussionsupporting

confidence: 90%

Cyclosporine A-Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation

et al. 2004

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Hyperlipidemia is a common side effect of cyclosporine A (CsA) after solid organ transplantation. CsA also markedly reduces the synthesis rate of bile salts in rats and can inhibit biliary bile salt secretion. It is not known, however, whether CsA inhibits the synthesis of bile salts in humans, and whether the hyperlipidemic effects of CsA are related to bile salt metabolism. Our objective was to assess the effects of CsA on the synthesis rate of bile salts and on plasma triglycerides and cholesterol levels in pediatric liver transplant patients. Before and after discontinuation of CsA treatment after liver transplantation, synthesis rate and pool size of the primary bile salts cholate and chenodeoxycholate were determined using a stable isotope dilution technique and related to plasma lipids. In 6 children (age: 3 -16 years) CsA treatment was discontinued at 2 years (median 2.3 years) after liver transplantation. Discontinuation of CsA increased synthesis rate of chenodeoxycholate (؉38%, P < .001) and cholate (؉21%, P < .05) and the pool size of chenodeoxycholate (؉54%, P < .001). Discontinuation of CsA decreased plasma levels of cholesterol ( -18%, P < .05) and triglycerides ( -23%, P < .05). Bile salt synthesis rate appeared to be inversely correlated with plasma cholesterol (Spearman rank correlation coefficient [r s ] ‫؍‬ -0.82, P < .01) and plasma triglyceride levels (r s ‫؍‬ -0.62, P < .05).

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Section: Discussionsupporting

confidence: 90%

Cyclosporine A-Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation

et al. 2004

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“…Our initial attempts to study bile acid kinetics in 8 patients after proctocolectomy and IPAA by use of a standardized protocol with serum samples taken once a day for 4 days [15,16,17,18,19] were unsuccessful. The decay of specific activity was too fast to adequately calculate fractional turnover and synthesis rates as well as pool sizes of endogenous bile acids.…”

Section: Discussionmentioning

confidence: 99%

“…Kinetics of primary bile acids were measured in a group of 8 patients as described previously, with postprandial venous blood samples taken before administration of the label and for the next 4 days, once a day [15,16,17,18,19]. Analysis of kinetics of the primary bile acids in these patients was unsuccessful because the specific activity decay was too rapid to calculate pool sizes, fractional turnover rates and synthesis rates.…”

Section: Methodsmentioning

confidence: 99%

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Kinetics of Primary Bile Acids in Patients after Proctocolectomy and Ileal Pouch-Anal Anastomosis

Gotthardt

Sauer²,

Schaible³

et al. 2014

Digestion

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Background: The high incidence of cholesterol gallstones in patients after proctocolectomy with ileal pouch-anal anastomosis (IPAA) may be due to an increased loss of bile acids. We aimed to evaluate the kinetics of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) in these patients. Methods: Pool sizes, synthesis rates, and fractional turnover rates of CA and CDCA were determined by combined capillary gas chromatography/isotope ratio mass spectrometry in serum samples after administration of [¹³C]CA and [¹³C]CDCA in 6 patients and 9 healthy volunteers. Results: In patients with IPAA, pool sizes of CA and CDCA were 11.5 (8.2-23.8) and 12.1 (6.7-20.1) µmol/kg, respectively, and were significantly lower than in healthy controls [36.0 (24-47) and 29.0 (21-42) µmol/kg, respectively; p < 0.05, each]. Fractional turnover rates of CA [1.19 (1.06-1.82) vs. 0.31 (0.13-0.54) per day] and CDCA [1.01 (0.50-1.63) vs. 0.23 (0.09-0.36) per day] were increased fourfold in patients with IPAA (p < 0.05, each). Synthesis rates of CDCA [10.2 (5.2-32.9) vs. 6.6 (2.7-10.5) µmol/kg per day, p = 0.05] and CA [15.1 (9.3-39.4) vs. 11.5 (3.1-20.5) µmol/kg per day, n.s.] tended to be higher in patients with IPAA than in controls. Conclusion: The reduced pool size of primary bile acids may contribute to the high incidence of cholesterol gallstones in patients after proctocolectomy and IPAA.

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“…1 Other short-term studies have examined bile composition after OLT in animals and in humans. [1][2][3][4][5][6][7] Biliary lipid synthesis and secretion are depressed initially but return to normal over the first 1 to 2 weeks after OLT. However, few studies have followed up on patients for longer than 2 to 3 weeks to determine the longer-term effects of OLT on the secretion of biliary cholesterol and phospholipids.…”

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confidence: 99%

Biliary lipid composition after liver transplantation: Effect of allograft function and cyclosporine

Kowdley

Haigh

et al. 1998

Liver Transpl

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Biliary lipid composition and bile flow are altered after orthotopic liver transplantation. Cyclosporine may have additional effects on biliary lipid composition and secretion. We studied the effects of liver transplantation, allograft function, and cyclosporine on biliary lipids in humans. Changes in lipid composition and secretion were correlated with serum cyclosporine levels, clinical events, and allograft function. Bile samples were withdrawn via a T-tube at interval time points in 17 patients during the first 3 months posttransplantation. Total and individual bile acid, cholesterol, and phospholipid were determined using high-performance liquid chromatography. Biliary lipid profiles were then correlated with clinical events, serum cyclosporine levels, and other clinical laboratory values. Biliary lipid concentrations decreased in 3 patients during periods of graft dysfunction (acute cellular rejection, drug-induced hepatitis, and inferior vena caval thrombosis) and increased with resolution of the graft injury. Serum cyclosporine levels were positively correlated with total bile acid, cholesterol, and phospholipid concentrations in bile. There was no relationship between the composition of secreted bile acids and serum cyclosporine levels. Bile acid, cholesterol, and phospholipid secretion were not uncoupled in the presence of cyclosporine. We concluded that (1) a decrease in biliary lipid concentrations may be an indicator of worsened graft function in some allografts; (2) biliary lipid concentrations are correlated with increasing cyclosporine levels; and (3) bile acid composition is unchanged, and uncoupling of secretion of other biliary lipids is not observed in the presence of cyclosporine.

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Kinetics of primary bile acids in patients after orthotopic liver transplantation

Cited by 9 publications

References 22 publications

Cyclosporine A-Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation

Cyclosporine A-Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation

Kinetics of Primary Bile Acids in Patients after Proctocolectomy and Ileal Pouch-Anal Anastomosis

Biliary lipid composition after liver transplantation: Effect of allograft function and cyclosporine

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