Prospective trial of penicillamine in primary sclerosing cholangitis

LaRusso, Nicholas F.; Wiesner, Russell H.; Ludwig, Jürgen; MacCarty, Robert L.; Beaver, Sandra J.; Zinsmeister, Alan R.

doi:10.1016/0016-5085(88)90180-1

Cited by 161 publications

(46 citation statements)

References 16 publications

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“…3). This histological finding was consistent with the first stage of for PSCpatients using immunosuppressive agents (4, 5), antifibrogenic agents (6,7), and combinations of these agents (8,9). However, there has been no evidence that the treatments mentioned above could improve the outcomes of PSCpatients.…”

Section: Case Reportsupporting

confidence: 70%

Paradoxical Progression of Biliary Strictures against Recovery of Biochemical Parameters under Ursodeoxycholic Acid Treatment in a Case of Primary Sclerosing Cholangitis with Ulcerative Colitis.

et al. 2000

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Ursodeoxycholic acid (UDCA) treatment for primary sclerosing cholangitis (PSC) has been considered a rational therapy, though its effectiveness in the clinical course is still open to discussion. In this report, we describe a 22-year-old man with PSCat an.early stage, which was associated with ulcerative colitis (UC). He showed progressive strictures of bile ducts over a 1.5-year period in spite of an improvement in the biochemical parameters by UDCA treatment. Therefore, care should be taken in interpreting the effectiveness of UDCA, because the biochemical parameters maynot change in parallel with the clinical course of PSC.

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Section: Case Reportsupporting

confidence: 70%

Paradoxical Progression of Biliary Strictures against Recovery of Biochemical Parameters under Ursodeoxycholic Acid Treatment in a Case of Primary Sclerosing Cholangitis with Ulcerative Colitis.

et al. 2000

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“…Moreover, there are no tools for screening and diagnosing the disease early enough (i.e., when it is amenable to treatment), well before irreversible strictures, fibrosis, and cirrhosis have developed. Most previous studies have evaluated the effect of immunosuppressive agents in PSC (e.g., prednisone, budesonide, azathioprine, methotrexate, and penicillamine) with completely negative or very limited effects, [21][22][23][24][25][26][27][28][29][30] suggesting that immunological factors probably play little or no role in the pathogenesis of PSC by the time marked strictures or cirrhosis have developed. PSC is a progressive disease leading to obstruction of bile ducts and cholestasis, which in turn leads to increased endotoxin levels in the portal space and activation of Kupffer cells and macrophages.…”

Section: Discussionmentioning

confidence: 99%

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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“…5,8 Numerous other drugs, including but not limited to azathioprine, budesonide, methotrexate and pentoxifylline, have also been evaluated in the treatment of PSC but without evidence of benefit. 2,4,[9][10][11][12][13][14][15] The negative results of these clinical trials have highlighted the importance of considering treatment approaches that target alternative pathophysiological pathways. Primary sclerosing cholangitis is now generally considered to be an idiopathic, likely immune-mediated disease with various aetiopathogenic components.…”

Section: Introductionmentioning

confidence: 99%

Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis ‐ a pilot study

Tabibian

Weeding

Jorgensen

et al. 2013

Aliment Pharmacol Ther

232

171

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Prospective trial of penicillamine in primary sclerosing cholangitis

Cited by 161 publications

References 16 publications

Paradoxical Progression of Biliary Strictures against Recovery of Biochemical Parameters under Ursodeoxycholic Acid Treatment in a Case of Primary Sclerosing Cholangitis with Ulcerative Colitis.

Paradoxical Progression of Biliary Strictures against Recovery of Biochemical Parameters under Ursodeoxycholic Acid Treatment in a Case of Primary Sclerosing Cholangitis with Ulcerative Colitis.

Metronidazole and Ursodeoxycholic Acid for Primary Sclerosing Cholangitis: A Randomized Placebo–Controlled Trial

Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis ‐ a pilot study

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