A Multicenter, Controlled Trial of Ursodiol for the Treatment of Primary Biliary Cirrhosis

Poupon, R; Balkau, Beverley; Eschwège, É.; Poupon, Raoul

doi:10.1056/nejm199105303242204

Cited by 702 publications

(388 citation statements)

References 34 publications

Supporting

Mentioning

364

Contrasting

Unclassified

Order By: Relevance

“…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: 94%

“…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).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2004

View full text Add to dashboard Cite

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.)

show abstract

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

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

et al. 2004

View full text Add to dashboard Cite

show abstract

“…19,21,30 Although the mechanism(s) of the UDCA effect on the improvement of liver function are still unclear, it has been postulated that UDCA, a less hydrophobic bile acid, displaces the more hydrophobic, potentially toxic bile acids from the membranes, protecting the hepatocytes. 31 Conversely, the immunomodulatory properties [32][33][34] as well as an antiapoptotic effect of UDCA 18 have been indicated.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 Furthermore, recent reports have indicated a variety of characteristics of UDCA in immunomodulation 17 and anti-apoptosis. 18 Despite its long history as a safe drug for patients with various hepatobiliary disorders, such as primary biliary cirrhosis 19,20 and chronic viral hepatitis, 21 the mechanism of action of UDCA has not been fully understood. In addition, although the improvement of biochemical data in patients with these chronic hepatic diseases has been reported, the benefit of its administration for patients in advanced stage has not been determined.…”

mentioning

confidence: 99%

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

et al. 2005

View full text Add to dashboard Cite

“…[1][2][3][4] In addition, a combined analysis, pooling 548 patients involved in three large trials using a similar dose of UDCA, has demonstrated that 4-year UDCA therapy increases survival free of orthotopic liver transplantation (OLT). 5 In untreated patients with PBC, elevated levels of serum bilirubin level (SBL) have been consistently found to be an independent predictor of a poor prognosis.…”

mentioning

confidence: 99%

Clinical Significance of Serum Bilirubin Levels Under Ursodeoxycholic Acid Therapy in Patients With Primary Biliary Cirrhosis

Bonnand

et al. 1999

Hepatology

View full text Add to dashboard Cite

We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA. Among UDCA-treated patients, we compared survival free of OLT in patients with normalized SBL (I17 mol/L) with those who had persistently elevated SBL. Difference in survival was tested between UDCA-treated patients whose SBL normalized with treatment and placebo patients who had normal baseline SBL. We evaluated, in each treatment group, the prognostic value of 6-month SBL. Survival was estimated using the Kaplan-Meier method and compared by the Cox model. Survival free of OLT was significantly longer in patients who had normalized SBL (P F .0001; relative risk [RR]: 3.7, UDCA group). Survival free of OLT was not significantly different between UDCA patients with normalized SBL and placebo patients with a normal baseline SBL (P ‫؍‬ .69). For several cutoffs of 6-month SBL, RRs of OLT or death were similar in UDCA-treated and placebo patients: the RR of OLT or death associated with a 6-month SBL more than 30 mol/L was 6.0 for UDCA and 5.7 for placebo groups. In conclusion, normalization of SBL during therapy is associated with improved clinical outcome. SBL under UDCA therapy is a prognostic factor in PBC. SBL under UDCA therapy should be interpreted as in untreated patients. (HEPATOLOGY 1999;29:39-43.)

show abstract

A Multicenter, Controlled Trial of Ursodiol for the Treatment of Primary Biliary Cirrhosis

Abstract: Ursodiol is a safe and effective treatment for primary biliary cirrhosis.

Cited by 702 publications

References 34 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

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡

Clinical Significance of Serum Bilirubin Levels Under Ursodeoxycholic Acid Therapy in Patients With Primary Biliary Cirrhosis

Contact Info

Product

Resources

About