Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: Results of a prospective double-blind trial

Leuschner, M.; Maier, K. P.; Schlichting, Julia; Strahl, S; Herrmann, G.; Dahm, Hans Helmut; Ackermann, Hanns; Happ, J.; Leuschner, U.

doi:10.1016/s0016-5085(99)70351-3

Cited by 240 publications

(136 citation statements)

References 22 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Improvement in biochemical and histologic parameters was observed in patients with early-stage PBC who were treated for 2 years in a controlled trial with budesonide and UDCA when compared with those treated with UDCA alone. 9 In contrast, in a second study that did not include placebo controls, combined treatment with UDCA and budesonide for 1 year led to marginal, if any, biochemical improvement and significant worsening of osteoporosis in a heterogeneous group of patients with early-and late-stage PBC. 15 In a heterogeneous group of patients with primary sclerosing cholangitis, 9 mg daily of budesonide improved serum liver tests but led to significant adverse drug reactions in some of the patients.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis

Hempfling¹,

et al. 2003

View full text Add to dashboard Cite

Budesonide has been discussed as a potential treatment option in primary biliary cirrhosis (PBC). Therefore, we studied the pharmacokinetics and pharmacodynamics of budesonide in patients with PBC stage I/II and stage IV. Twelve patients with early PBC stage I/II and 7 patients with PBC stage IV under continuous treatment with ursodeoxycholic acid (UDCA) were enrolled in an exploratory trial. Each patient received oral budesonide for 3 weeks at weekly increasing dosages of 3 mg once to thrice per day. Budesonide and cortisol plasma levels, urinary cortisol excretion, serum liver tests, and immunoglobulins were determined on days 1, 7, and 21 of the study. Patients with PBC stage IV showed significantly higher peak plasma concentrations

show abstract

Section: Discussionmentioning

confidence: 97%

“…9 However, long-term treatment with conventional corticosteroids such as prednisone or prednisolone may be hampered by severe systemic side effects.…”

mentioning

confidence: 99%

Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis

Hempfling¹,

et al. 2003

View full text Add to dashboard Cite

show abstract

“…When adequate UDCA therapy - i.e., daily administration of high doses of this hydrophilic bile acid - is initiated at early stages (I-II) of the disease, about 60% of PBC patients normalize their biochemical parameters and reach a survival comparable to that in the general population (8,9). There are reports suggesting that the remaining patients who exhibit a suboptimal response to UDCA alone may experience some benefit when UDCA therapy is combined with glucocorticoids (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells

Arenas¹,

Hervías²,

Úriz³

et al. 2008

J. Clin. Invest.

View full text Add to dashboard Cite

Primary biliary cirrhosis (PBC) is a cholestatic disease associated with autoimmune phenomena and alterations in both biliary bicarbonate excretion and expression of the bicarbonate carrier AE2. The bile acid ursodeoxycholic acid (UCDA) is currently used in treatment of cholestatic liver diseases and is the treatment of choice in PBC; however, a subset of PBC patients respond poorly to UDCA monotherapy. In these patients, a combination of UDCA and glucocorticoid therapy appears to be beneficial. To address the mechanism of this benefit, we analyzed the effects of UDCA and dexamethasone on AE2 gene expression in human liver cells from hepatocyte and cholangiocyte lineages. The combination of UDCA and dexamethasone, but not UDCA or dexamethasone alone, increased the expression of liver-enriched alternative mRNA isoforms AE2b1 and AE2b2 and enhanced AE2 activity. Similar effects were obtained after replacing UDCA with UDCA conjugates. In in vitro and in vivo reporter assays, we found that a UDCA/dexamethasone combination upregulated human AE2 alternate overlapping promoter sequences from which AE2b1 and AE2b2 are expressed. In chromatin immunoprecipitation assays, we demonstrated that combination UCDA/dexamethasone treatment induced p300-related interactions between HNF1 and glucocorticoid receptor on the AE2 alternate promoter. Our data provide a potential molecular explanation for the beneficial effects of the combination of UDCA and glucocorticoids in PBC patients with inadequate response to UDCA monotherapy.

show abstract

“…38 Two recent studies have evaluated the potential therapeutic benefit of budesonide, a corticosteroid with an extensive firstorder hepatic metabolism and theoretically minimal systemic availability in patients with PBC. 39,40 In naive PBC patients, the combination of budesonide and UDCA led to a greater improvement in alkaline phosphatase activity, AST, and immunoglobulins as well as an impressive improvement in the degree of inflammation and fibrosis on liver biopsy than that seen with UDCA alone. 39 Unfortunately, the effect of such a combination on the Mayo risk score or serum bilirubin levels was not reported, and thus, the effect of budesonide on these important surrogate prognostic markers remained uncertain.…”

Section: Discussionmentioning

confidence: 99%

Silymarin in the Treatment of Patients With Primary Biliary Cirrhosis With a Suboptimal Response to Ursodeoxycholic Acid

Angulo

2000

Hepatology

View full text Add to dashboard Cite

Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC), but some patients show an incomplete response. Silymarin is a potent antioxidant with immunomodulatory and antifibrotic properties. The aim of this study was to evaluate the safety and assess the efficacy of silymarin in patients with PBC who had shown a suboptimal response to UDCA. Twenty-seven patients with PBC who had been on UDCA (13-15 mg/kg/day) therapy for 7 to 221 months and had shown a persistent elevation of alkaline phosphatase activity at least 2 times the upper limit of normal for more than 6 months were enrolled. Oral silymarin, 140 mg 3 times daily was given for 1 year, and patients continued on the same dosage of UDCA. No significant changes in serum alkaline phosphatase activity (897 ؎ 84 vs. 876 ؎ 95, P ‫؍‬

show abstract

Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: Results of a prospective double-blind trial

Cited by 240 publications

References 22 publications

Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis

Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis

Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells

Silymarin in the Treatment of Patients With Primary Biliary Cirrhosis With a Suboptimal Response to Ursodeoxycholic Acid

Contact Info

Product

Resources

About