Effects of Ursodeoxycholic Acid in Patients With Intrahepatic Cholestasis of Pregnancy

Palma, José Luis; Reyes, Humberto; Ribalta, J; Iglesias, J; Gonazalez, Manuel C.; Hernández, Ismael; Άlvarez, C. Barbazán; Molina, Cristina Guerrero; Danitz, Ana Maria

doi:10.1002/hep.1840150612

Cited by 151 publications

(76 citation statements)

References 42 publications

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“…[7][8][9][10][11][12][23][24][25] The mechanism of action of UDCA in hepatobiliary diseases is still not completely understood. 26 -38 Decreased intestinal absorption of hydrophobic, hepatotoxic bile acids, 39,40 and biliary enrichment with hydrophilic, nontoxic UDCA changes the balance of biliary bile acids in favor of nontoxic hydrophilic bile acids, and this change may represent one of the mechanisms of action of UDCA.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

et al. 2004

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“…The mitochondria were then rinsed with 0.1 M PIPES buffer, pH 7.3, followed by a 20 min postfix incubation at room temperature in 2% cacodylate-buffered OsO 4 . Next, the mitochondria were dehydrated using progressive concentrations of ethanol, infiltrated with propylene oxide, and embedded in Epon 812/Aralide 502 resin (Electron Microscopy Sciences, Fort Washington, PA, USA).…”

Section: Electron Microscopymentioning

confidence: 99%

Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation

et al. 1999

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The hydrophilic bile salt ursodeoxycholic acid (UDCA) is a potent inhibitor of apoptosis. In this paper, we further characterize the mechanism by which UDCA inhibits apoptosis induced by deoxycholic acid, okadaic acid and transforming growth factor b1 in primary rat hepatocytes. Our data indicate that coincubation of cells with UDCA and each of the apoptosis-inducing agents was associated with an approximately 80% inhibition of nuclear fragmentation (P50.001). Moreover, UDCA prevented mitochondrial release of cytochrome c into the cytoplasm by 70 ± 75% (P50.001), thereby, inhibiting subsequent activation of DEVD-specific caspases and cleavage of poly(ADP-ribose) polymerase. Each of the apoptosis-inducing agents decreased mitochondrial transmembrane potential and increased mitochondrial-associated Bax protein levels. Coincubation with UDCA was associated with significant inhibition of these mitochondrial membrane alterations. The results suggest that the mechanism by which UDCA inhibits apoptosis involves an interplay of events in which both depolarization and channel-forming activity of the mitochondrial membrane are inhibited.

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“…Most likely, the withdrawn of UDCA at the 7th week of gestation triggered the onset of cholestasis with pruritus. Although UDCA has been widely and successfully used in the second and third trimesters of pregnancy in women with intrahepatic cholestasis of pregnancy (ICP) [3,4] , we stopped its administration early during the first trimester of pregnancy of our patient for the lack of teratogenic effects of the drug is not well established in early pregnancy.…”

Section: Discussionmentioning

confidence: 98%

Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus

Lemoine¹,

Revaux²,

Francoz³

et al. 2008

WJG

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Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.

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Effects of Ursodeoxycholic Acid in Patients With Intrahepatic Cholestasis of Pregnancy

Cited by 151 publications

References 42 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

Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation

Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus

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