New treatment strategies for primary sclerosing cholangitis

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Primary sclerosing cholangitis (PSC) is a progressive liver disease without adequate treatment. Because the pathogenesis of PSC is not well understood, specific therapies designed to alter the pathogenesis are not available. Animal models suggest a link between bacterial overgrowth, lipopolysaccharides from the bacterial cell walls and stimulation of endogenous TNF formation which can be inhibited by pentoxifylline. Unfortunately, in humans treated with pentoxifylline, little effect was seen. Antibiotics such as metronidazole, vancomycin, tetracycline and azithromycin in small studies show biochemical improvement. Docosahexanoic acid has been used for treating patients in a small pilot study and led to some improvement in liver biochemistries. Immunologic abnormalities have been considered to be potentially important. Attempts to treat PSC with mycophenolate mofetil and tacrolimus have been largely unsuccessful. Budesonide has shown a limited benefit, but perhaps more so in patients with elevated IgG4 levels. PSC is characterized by marked fibrosis. Modulation of the renin-angiotensin system as well as use of rapamycin may reduce fibrosis, but data from this approach has been scant. Bile acids have been tested, but initial doses used in primary biliary cirrhosis led only to biochemical improvement. Higher doses of ursodeoxycholic acid (28-30 mg/kg/day) seemed to be associated with a worsening outcome. Intermediate doses have been tested in a study where biochemical improvement was seen and trends towards enhanced survival were found, but only about two thirds of the anticipated enrollment occurred. Currently, there are multiple potential therapeutic avenues to explore for patients with PSC, and it is hoped that one of these will lead to identification of a proven therapy for this disease.

Original languageEnglish (US)
Pages (from-to)113-116
Number of pages4
JournalDigestive Diseases
Volume29
Issue number1
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Keywords

  • Antibiotics
  • Primary sclerosing cholangitis
  • Ursodeoxycholic acid

ASJC Scopus subject areas

  • Gastroenterology

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