Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: A 30-month pilot study

Abstract

We investigated the effects of once-daily oral administration of 10 mg/kg ursodeoxycholic acid (generic name, ursodiol) on elevated serum enzyme activities, bilirubin, cholesterol, bile acids and symptoms in patients with primary sclerosing cholangitis. A 30-mo, open-label, pilot trial was designed to cover four periods: (a) 3 mo of pretreatment observation (period 1), (b) 6 mo on ursodiol (period 2), (c) 3 mo withdrawal of treatment (period 3) and (d) 18 mo of extended retreatment (period 4). Diagnosis was confirmed by cholangiography and liver biopsy specimens. We enrolled 12 patients with persistently elevated pretreatment alkaline phosphatase and gamma-glutamyltransferase levels (at least twice the upper limit of normal), and observed them for a median of 37 mo. Significant reductions in serum total cholesterol levels and in serum enzyme activities indicating cholestasis and hepatocellular injury occurred during ursodiol treatment in both treatment periods 2 and 4 and relapsed with treatment interruption in period 3. Elevated serum bilirubin and symptoms of disabling fatigue, pruritus and diarrhea were improved by ursodiol. Improvements have continued after 2 yr of treatment in 10 patients (1 patient had a transplantation after he relapsed on withdrawal of ursodiol therapy; another died of postoperative complications of colon resection for carcinoma). No other cases of clinical deterioration were observed in the retreatment period. The longer term reductions of alkaline phosphatase, transaminases, bilirubin and cholesterol after 2 yr of treatment were even greater than the initial reductions after 6 mo of treatment. These results justify initiation of larger, controlled clinical trials, with serial morphological evaluations of the liver and biliary tree.

Fibrates suppress chenodeoxycholic acid-induced RANTES expression through inhibition of NF-κB activation

“…Ursodeoxycholic acid, which is a 7 isomer of chenodeoxycholic acid, is considered to be a nonhepatotoxic hydrophilic bile acid that may reverse potential hepatotoxicity of endogenous bile acids (Heuman et al, 1991), and is often used in patients with cholestasis to improve liver dysfunction (Lindor and Burnes, 1991;O'Brien et al, 1991;Bouchard et al, 1993). Notably, a beneficial effect of ursodeoxycholic acid in patients with primary biliary cirrhosis has been demonstrated in double-blind controlled studies (Leuschner et al, 1989;Poupon et al, 1991;Corpechot et al, 2000).…”

Intrahepatic Cholestatic Syndromes: Pathogenesis, Clinical Features and Management

“…UDCA has been found to be of some efficacy in perception of pruritus in some patients [54]. The mechanism of action is unclear although it is possible that both PBC [47,48] and PSC in providing symptomatic relief (pruritus and fatigue) and inducing some histologic endogenous opioid peptides play a role in causing pruritus. At present, the use of opiate antagonists remains improvement, although any beneficial effect on the longterm prognosis is controversial at present.…”

Ursodeoxycholic acid: A therapeutic niche in an internist’s practice

“…Прием УДХК в средних (13-15 мг/кг) и высоких (25-30 мг/кг) дневных дозах приводил к улучшению биохимических и гистологических параметров в пилотных иссле-дованиях [33][34][35]. В настоящее время отношение к этому препа-рату при лечении ПСХ неоднозначно.…”