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  • Title: Bile acid changes after high-dose ursodeoxycholic acid treatment in primary sclerosing cholangitis: Relation to disease progression.
    Author: Sinakos E, Marschall HU, Kowdley KV, Befeler A, Keach J, Lindor K.
    Journal: Hepatology; 2010 Jul; 52(1):197-203. PubMed ID: 20564380.
    Abstract:
    UNLABELLED: High-dose (28-30 mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), because of limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high-dose UDCA versus placebo. Samples for analysis were obtained at the baseline and at the end of treatment. The mean changes in the UDCA level (16.86 versus 0.05 micromol/L) and total bile acid level (17.21 versus -0.55 micromol/L) were significantly higher in the UDCA group (n = 29) versus the placebo group (n = 27) when pretreatment levels were compared (P < 0.0001). LCA was also markedly increased (0.22 versus 0.01 micromol/L) in the UDCA group compared to the placebo group (P = 0.001). No significant changes were detected for cholic acid, deoxycholic acid, or chenodeoxycholic acid. Patients (n = 9) in the UDCA group who reached clinical endpoints of disease progression (the development of cirrhosis, varices, liver transplantation, or death) tended to have greater increases in their posttreatment total bile acid levels (34.99 versus 9.21 micromol/L, P < 0.08) in comparison with those who did not. CONCLUSION: High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool, including LCA.
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