Bile acid metabolism and biliary secretion in patients receiving orthotopic liver transplants: Differing effects of cyclosporine and FK 506

McCashland, Timothy M.; Donovań, John M.; Amelsberg, A.; Rossi, Steven S.; Hofmann, Alan F.; Shaw, Byers W.; Quigley, Eamonn M.M.

doi:10.1002/hep.1840190611

Cited by 21 publications

(22 citation statements)

References 38 publications

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“…28 However, the latter is markedly impaired in transplant recipients, especially when receiving cyclosporine A. 29 Accordingly, spontaneous bile flow rate and bile acid secretion are very low within the first 5 days after OLT.…”

Section: Discussionmentioning

confidence: 99%

In liver transplantation, T tube bile represents total bile flow: Physiological and scintigraphic studies on biliary secretion of organic anions

et al. 1999

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The present study was performed to clarify the recovery of hepatocellular uptake and the biliary secretion of bile acids during the first 14 days after orthotopic liver transplantation (OLT) and to determine the fraction of bile flow appearing outside through the T tube and entering the duodenum. Therefore, we determined primary and secondary bile acids in bile samples obtained from the T tube at day 5 after OLT, while the T tube was permanently open, and at days 10 and 14 after OLT, i.e., 4 and 9 days after closure of the T tube, respectively, thus restoring enterohepatic bile acid circulation. In addition, we performed hepatobiliary scintigraphy using technetium 99m-labeled [2,4,6 trimethyl-3-bromo]imino-diacetic acid (technetium 99m-BRIDA) in 12 patients between days 4 and 17 after OLT. Chromatographic analyses of biliary bile acids showed no secondary bile acids during the first 5 days after OLT, as opposed to 10 and 14 days after OLT when enterohepatic circulation was restored. Eleven patients with an uncomplicated postoperative course after OLT showed a significantly reduced hepatic uptake and biliary secretion of 99m Tc-BRIDA during the first days after OLT with progressive recovery. One patient with an acute allograft rejection episode showed almost no uptake and only minimal secretion. The bile fraction appearing outside through the inserted T tube represented 94.6% ؎ 6.2% of the injected 99m Tc-BRIDA. We conclude that OLT results in markedly impaired hepatocellular uptake and biliary secretion of organic anions. Simultaneously, bile acid synthesis is significantly reduced, which, in addition, diminishes bile secretion of the graft. We show that T tube bile is a valid tool for bile physiological studies in patients in whom transplantation was successfully performed.

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Section: Discussionmentioning

confidence: 99%

In liver transplantation, T tube bile represents total bile flow: Physiological and scintigraphic studies on biliary secretion of organic anions

et al. 1999

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“…Regarding change in bile acid component after administration of TCR, little clinical evidence has been reported [S, 16,241. Our study showed that TCR increased bile acid synthesis rate, mainly CA synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, CsA reduced the bile acid synthesis rate in a dose-dependent manner, caused by the suppression of CDCA synthesis. An increase in CA to CDCA ratio in bile composition after liver transplantation might be dependent on elevation of CA and/or decrease in CDCA [S, 16,241. Sauer et al [24] demonstrated that the secre'-tion rate of CDCA in TCR-treated patients was not different from healthy non-treated controls, whereas that of CA significantly increased.…”

Section: Discussionmentioning

confidence: 99%

Influence of tacrolimus on bile acid and lipid composition in continuously drained bile using a rat model.

Mizuta¹,

Kobayashi²,

Uchida³

et al. 1999

Transplant Int

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Cholestatic effects have been reported for cyclosporine (CsA), but information is still limited for tacrolimus (TCR). The purpose of this study was to investigate the influence of TCR on biliary bile acid and lipid composition as compared with CsA, using a continuously bile-drained rat model. Adult male Wistar rats received TCR (0.4 mg/kg, 1 mg/kg, and 4 mg/kg) or CsA (2.5 mg/kg, 10 mg/kg, and 25 mg/kg) by intramuscular injection (i. m.) daily for 10 days.

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“…Such modifications in bile composition are probably due to the influence of immunosuppressive drugs [28,29] . Both experimental [26,[29][30][31] and clinical studies [32][33][34] bile acid composition when compared to normal grafts [35] . Bile cytotoxicity (measured by an increase in the bile salt/phospholipid ratio) appears to be involved in the pathogenesis of non-anastomotic biliary strictures [36,37] .…”

Section: Liver Transplantationmentioning

confidence: 99%

Bile Changes after Liver Surgery: Experimental and Clinical Lessons for Future Applications

et al. 2010

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Introduction: The aim of this review is to summarize the available evidence for changes in bile composition following liver surgery and assess their use in predicting post-operative complications. Materials and Methods: A literature search was undertaken for all studies focusing on bile composition, bile volume and analysis. Articles were selected from MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases up to May 2009. Results: Low values of pre-operative bilirubin diglucuronide predict reduced post-operative liver function and the occurrence of jaundice. Low concentrations of hepatocyte growth factor and interleukin-6 in bile following surgery are associated with the subsequent development of liver failure and are probably surrogate markers for situations where the resultant hepatic regeneration is inadequate. Conclusions: Analysis of the composition and quality of bile is probably underused as a tool for the pre-operative screening and early post-operative monitoring of patients at high risk of developing liver failure following major hepatobiliary procedures.

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Bile acid metabolism and biliary secretion in patients receiving orthotopic liver transplants: Differing effects of cyclosporine and FK 506

Cited by 21 publications

References 38 publications

In liver transplantation, T tube bile represents total bile flow: Physiological and scintigraphic studies on biliary secretion of organic anions

In liver transplantation, T tube bile represents total bile flow: Physiological and scintigraphic studies on biliary secretion of organic anions

Influence of tacrolimus on bile acid and lipid composition in continuously drained bile using a rat model.

Bile Changes after Liver Surgery: Experimental and Clinical Lessons for Future Applications

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