Ursodeoxycholic acid in primary biliary cirrhosis: Results of a controlled double-blind trial

Leuschner, U.; Fischer, H; Kurtz, W; Güldütuna, S.; Hübner, K.; Hellstern, A; Gatzen, M.; Leuschner, M.

doi:10.1016/0016-5085(89)91698-3

Cited by 338 publications

(136 citation statements)

References 20 publications

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“…UDCA has been shown to improve liver function tests, liver histology, and survival in primary biliary cirrhosis, [1][2][3][4][5][6] and similar effects have been observed in other cholestatic diseases. [7][8][9][10][11][12][23][24][25] The mechanism of action of UDCA in hepatobiliary diseases is still not completely understood.…”

Section: Discussionmentioning

confidence: 58%

“…In primary biliary cirrhosis, UDCA treatment slows progression of the disease and improves survival. [1][2][3][4][5][6] In primary sclerosing cholangitis (PSC), UDCA improves laboratory parameters, [7][8][9][10][11][12] and its effect on the outcome is currently being evaluated. There is evidence 11,12 that high doses (Ն20 mg/kg/d) of UDCA may be more effective than average doses (15 mg/kg/d).…”

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confidence: 99%

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Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

et al. 2004

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Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseases. In primary sclerosing cholangitis (PSC), there is evidence that high doses (؎20 mg/kg) of UDCA may be more effective than average doses. Biliary enrichment of UDCA at such high doses may represent the decisive factor for its beneficial effect. Up to now it is not clear how high-dose UDCA correlates with its biliary enrichment and whether bacterial degradation of large amounts of UDCA may lead to an increased bacterial formation of more toxic hydrophobic bile acids. We determined the biliary bile acid composition in 56 patients with PSC including 30 patients with repeat bile samples treated with various doses of UDCA. At a UDCA dose of 10 -13 mg/kg/d (n ‫؍‬ 18) biliary UDCA represented 43.1% ؉ 0.3% (mean ؉ SD) of total bile acids; at a UDCA dose of 14 -17 mg/kg (n ‫؍‬ 14), its biliary content increased to 46.9% ؉ 0.3%, at 18 -21 mg/kg (n ‫؍‬ 34) to 55.9% ؉ 0.2%, at 22-25 mg/kg (n ‫؍‬ 12) to 58.6% ؉ 2.3%, and at 26 -32 mg/kg (n ‫؍‬ 8) to 57.7% ؉ 0.4%. During UDCA treatment, the biliary content of all other bile acids was unchanged or decreased. In conclusion, biliary enrichment of UDCA increases with increasing dose and reaches a plateau at 22-25 mg/kg. There was no increase of toxic hydrophobic bile acids. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, it seems likely that UDCA doses of up to 22-25 mg/kg may be more effective than lower doses. (HEPATOLOGY 2004;40:693-698.)

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Section: Discussionmentioning

confidence: 58%

mentioning

confidence: 99%

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

et al. 2004

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“…Notably, a beneficial effect of ursodeoxycholic acid in patients with primary biliary cirrhosis has been demonstrated in double-blind controlled studies (Leuschner et al, 1989;Poupon et al, 1991;Corpechot et al, 2000). Additionally, it was recently reported that bezafibrate, a hypolipidemic agent, is effective in primary Y.…”

Section: Introductionmentioning

confidence: 98%

Fibrates suppress chenodeoxycholic acid-induced RANTES expression through inhibition of NF-κB activation

Hirano

Fujii

et al. 2002

European Journal of Pharmacology

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Fibrates, hypolipidemic agents, are reported to be effective in treatment of primary biliary cirrhosis. However, the mechanism involved in therapeutic benefits of fibrates in primary biliary cirrhosis remains unknown. In contrast, hepatic regulated upon activation, normal T-cell expressed and secreted (RANTES) is increased in patients with primary biliary cirrhosis and bile acids up-regulate RANTES expression in hepatocytes. The role of fibrates in bile acid-induced RANTES expression was investigated in human hepatoma cells; 100 µM of bezafibrate and fenofibrate decreased expression of chenodeoxycholic acid-induced RANTES mRNA and protein. In addition, luciferase enzyme assay using RANTES promoter-luciferase reporter plasmid revealed that 100 µM of bezafibrate and fenofibrate transcriptionally reduced chenodeoxycholic acid-induced RANTES gene expression. Moreover, bezafibrate clearly repressed DNA-binding activity of nuclear factor-B (NF-B) induced by chenodeoxycholic acid. Therefore, fibrates might be inhibitory agents of inflammatory cell migration by RANTES to the liver in patients with primary biliary cirrhosis, possibly indicating that fibrates are therapeutic agents in primary biliary cirrhosis.

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“…der Gallengangsinfiltration durch PDC-E2 spezifische CD4+ und CD8+T-Lymphozyten eine wesentliche Rolle zugeschrieben. Diese spezifischen T-Zellen sind im Vergleich zum peripheren Blut in der Leber angereichert (17,18,35 (9,13,21,24,27,36). Bei Nicht-Ansprechen der UDC-Therapie sollte die Diagnose der PBC in Zweifel gezogen werden.…”

Section: äTiologie Und Pathogeneseunclassified

Cholestatic liver diseases: primary biliary cirrhosis

Thimme

Og²,

Kreisel³

2002

Dtsch med Wochenschr

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Anamnese und klinischer Befund: Eine 42-jährige Patientin klagt über einen bereits seit einem Jahr bestehenden Juckreiz, der im letzten halben Jahr stark zugenommen hat. Sie fühlt sich zunehmend müde und weniger leistungsfähig und leidet unter Mundtrockenheit. Ernste Vorerkrankungen bestehen nicht, Medikamente nimmt sie nicht ein. Es fallen ein leicht gelbliches Hautkolorit, ein diskreter Sklerenikterus sowie Xanthelasmen auf. An Armen und Stamm finden sich zahlreiche, teils bereits vernarbte Kratzspuren. Herz und Lunge sind unauffällig, die Leber palpatorisch konsistenzvermehrt aber nicht vergrößert, die Milz nicht tastbar. Der Blutdruck misst 130/80 mmHg.

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Ursodeoxycholic acid in primary biliary cirrhosis: Results of a controlled double-blind trial

Cited by 338 publications

References 20 publications

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis

Fibrates suppress chenodeoxycholic acid-induced RANTES expression through inhibition of NF-κB activation

Cholestatic liver diseases: primary biliary cirrhosis

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