A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis

Mitchell, Stephen; Bansi, D; Hunt, Nicholas; Bergmann, Klaus von; Fleming, K. A.; Chapman, Roger W.

doi:10.1053/gast.2001.27965

Cited by 319 publications

(212 citation statements)

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“…A recent Scandinavian study demonstrated that patients with PSC who were treated with UDCA while on a waiting list for liver transplantation had significantly fewer cholangiocarcinomas than patients who did not receive UDCA therapy, suggesting that even a standard dose of UDCA may have a positive effect on the clinical outcome of the disease. 40 Very few studies have actually evaluated the effect of UDCA on ERCP changes, 3,14,41 one of them demonstrating that it does not prevent major bile duct occlusion even during therapy lasting up to 13 years, 41 making it questionable that a higher dose can really improve cholangiographic appearance within 2 years. 14 In the present study, we excluded patients with end-stage liver disease, and half of the patients were actually asymptomatic and had intrahepatic disease of only 3.4 years' mean duration (range, 0-18 years).…”

Section: Discussionmentioning

confidence: 99%

“…40 Very few studies have actually evaluated the effect of UDCA on ERCP changes, 3,14,41 one of them demonstrating that it does not prevent major bile duct occlusion even during therapy lasting up to 13 years, 41 making it questionable that a higher dose can really improve cholangiographic appearance within 2 years. 14 In the present study, we excluded patients with end-stage liver disease, and half of the patients were actually asymptomatic and had intrahepatic disease of only 3.4 years' mean duration (range, 0-18 years). In liver histology, stage was normal in 28% of patients in both groups, whereas only 2 patients in the UDCA/placebo group and 3 in the UDCA/MTZ group had cirrhosis at liver biopsy.…”

Section: Discussionmentioning

confidence: 99%

“…13,36 UDCA therapy significantly improved liver biochemistry in both groups in accordance with previous findings. 13,14,36 Marked inflammation (grades 3-4), seen in 31% of patients in the UDCA/placebo group and in 38% of patients in the UDCA/MTZ group, suggests a chronically active disease process. The slight improvement in liver histology both in stage and in grade seen in UDCA/MTZ therapy versus UDCA alone would suggest an anti-inflammatory effect of MTZ.…”

Section: Discussionmentioning

confidence: 99%

“…14 We included the control ERCP in the study protocol because classification and staging of cholangiographic abnormalities has been shown to have prognostic value. 44 In those patients in whom comparable examinations with adequate filling were available, a trend showing either improvement or no progression of the disease was seen in the UDCA/MTZ group compared with those on UDCA monotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study with 2 years' follow-up, a higher dose of UDCA (20 mg/kg/d) appears to have a beneficial effect on both liver histology and cholangiographic findings at ERCP. 14 Only one small, uncontrolled long-term study using antibiotics in the treatment of PSC has been published so far. 15 The study compared tetracycline, steroid therapy, and colectomy in the management of PSC, demonstrating that none of the strategies had a beneficial effect on the clinical course of the disease.…”

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Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

et al. 2004

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No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo-controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/ MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases ␥-glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (؊337 ؎ 54 U/L, P < .05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (؊0.50 ؎ 0.13, P < .01). The number of patients with improvement of stage (P < .05) and grade (P < .05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long-term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated. (HEPATOLOGY 2004;40:1379 -1386

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

et al. 2004

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Bile acids for primary sclerosing cholangitis

Chen¹,

Gluud²

2003

Cochrane Database of Systematic Reviews

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Bile acids for primary sclerosing cholangitis

Poropat

Giljača

Stimac

et al. 2011

Cochrane Database of Systematic Reviews

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BackgroundPrimary sclerosing cholangitis is a progressive chronic cholestatic liver disease that usually leads to the development of cirrhosis. Studies evaluating bile acids in the treatment of primary sclerosing cholangitis have shown a potential benefit of their use. However, no influence on patients survival and disease outcome has yet been proven. ObjectivesTo assess the beneficial and harmful e ects of bile acids for patients with primary sclerosing cholangitis. Search methodsWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded generally from inception through to October 2010. Selection criteriaRandomised clinical trials comparing any dose of bile acids or duration of treatment versus placebo, no intervention, or another intervention were included irrespective of blinding, language, or publication status. Data collection and analysisTwo authors extracted data independently. We evaluated the risk of bias of the trials using prespecified domains. We performed the metaanalysis according to the intention-to-treat principle. We presented outcomes as relative risks (RR) or mean di erences (MD), both with 95% confidence intervals (CI). Main resultsEight trials evaluated ursodeoxycholic acid versus placebo or no intervention (592 patients). The eight randomised clinical trials have a high risk of bias. Patients were treated for three months to six years (median three years). The dosage of ursodeoxycholic acid used in the trials ranged from low (10 mg/kg body weight/day) to high (28 to 30 mg/kg body weight/day). Ursodeoxycholic acid did not significantly reduce the risk of death (RR 1.00; 95% CI 0.46 to 2.20); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 1.22; 95% CI 0.91 to 1.64); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.60; 95% CI 0.23 to 1.57). Ursodeoxycholic acid significantly improved serum bilirubin (MD -14.6 µmol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (MD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (MD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (MD -260 IU/litre; 95% CI -315 to -205), but not albumin (MD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was safe and well tolerated by patients with primary sclerosing cholangitis.Bile acids for primary sclerosing cholangitis (Review)

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A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis

Cited by 319 publications

References 46 publications

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

Bile acids for primary sclerosing cholangitis

Bile acids for primary sclerosing cholangitis

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