High dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis is safe and effective

Cullen, Susan N.; Rust, Christian; Fleming, K. A.; Edwards, Cathryn; Beuers, Ulrich; Chapman, Roger W.

doi:10.1016/j.jhep.2007.12.023

Cited by 124 publications

(85 citation statements)

References 21 publications

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“…In another randomized trial that included 219 patients, a higher dosage of UDCA treatment (17-23 mg/kg/day) did not result in any benefit in terms of mortality, need for OLT, or cholangiocarcinoma risk (Olsson, 2005). A pilot study reported that a very high dosage of UDCA (28-30 mg/kg/day) might improve survival (Cullen et al, 2008) ,however, a large multicenter randomized controlled trial was terminated prematurely due to side effects in the treatment arm (Lindor et al, 2009). UDCA treatment can prevent colonic neoplasia in PSC-IBD patients (Tung et al, 2001).…”

Section: Managementmentioning

confidence: 97%

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

Erkan¹

2011

Ulcerative Colitis - Epidemiology, Pathogenesis and Complications

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Section: Managementmentioning

confidence: 97%

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

Erkan¹

2011

Ulcerative Colitis - Epidemiology, Pathogenesis and Complications

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“…Some studies have shown a mild improvement in serum liver chemistry, however the evidence on liver histology remains unchanged. A study was done to evaluate the use of high dose UDCA to determine whether the change in the bile acid pool would affect the outcome of PSC patients (Cullen 2008). Thirty-one patients were randomized to 10 mg/kg, 20 mg/kg or 30 mg/kg of UDCA daily for 2 years.…”

Section: Medical Treatment For Pscmentioning

confidence: 99%

Primary Sclerosing Cholangitis and Ulcerative Colitis

Jagroop¹,

Rajapakse²

2012

Ulcerative Colitis From Genetics to Complications

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“…Ursodeoxycholic acid (UDCA) monotherapy is the only therapy in PSC for which improvement in serum liver tests has consistently been observed in placebo-controlled studies [24][25][26][27][28][29] , At doses of > 20 mg/kg/d of UDCA, surrogate markers of prognosis like the Mayo risk score have been shown to be improved in small cohorts of patients suggesting that "high dose UDCA" may represent an efficient treatment of PSC 29,30 . However, an obvious survival benefit with UDCA treatment has not been shown in PSC and no single study published so far fulfills the criteria of adequate sample size, adequate duration of follow-up and/or adequate dose of UDCA treatment in order to be able to prove or disprove a survival benefit of UDCA in PSC.…”

Section: Current Therapeutic Approachesmentioning

confidence: 99%

“…The largest trial from Scandinavia analyzed data from 198 patients being treated over 5 years with daily doses of 17-23 mg/kg. Unfortunately, this trial was underpowered (power analysis a priori: n=346), and the biochemical response of patients was unexpectedly poor when compared to smaller randomized, controlled trials using comparable doses of UDCA 24,26,27,29 . Data from a large randomized, long-term trial on "high dose UDCA" in PSC supported by the NIH have to be awaited before a firmer conclusion on the efficacy of "high dose UDCA" in PSC can be drawn.…”

Section: Current Therapeutic Approachesmentioning

confidence: 99%

Medical Treatment of Primary Sclerosing Cholangitis: A Role for Novel Bile Acids and other (post-)Transcriptional Modulators?

Beuers

Kullak‐Ublick

Pusl³

et al. 2008

Clinic Rev Allerg Immunol

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Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult. Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregnane-X receptor (PXR), vitamin D receptor (VDR), and peroxisome-proliferator-activator receptors (PPARs) have been shown to induce expression of diverse carriers and biotransformation enzymes of the intestinal and hepatic detoxification machinery and/or to modulate fibrogenesis. Pros and cons of respective receptor agonists for the future treatment of PSC are discussed in detail. In our view, the novel bile acid norUDCA and agonists of PPARs, VDR, and PXR appear particularly attractive for further studies in PSC. Beuers et al.: Future treatment of PSC Clinical Reviews in Allergy and Immunology 2008In press Medical treatment of primary sclerosing cholangitis: AbstractPrimary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic making the development of targeted therapeutic strategies difficult. Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical, and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregna...

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High dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis is safe and effective

Cited by 124 publications

References 21 publications

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis and Ulcerative Colitis

Medical Treatment of Primary Sclerosing Cholangitis: A Role for Novel Bile Acids and other (post-)Transcriptional Modulators?

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