Purpose: To explain the rationale supporting the use of ursodiol (ursodeoxycholic acid) for the treatment of patients with cholesterol gallstones and chronic liver diseases and to describe the results obtained in clinical trials.
Data Sources: Personal databases of the authors and MEDLINE were used to identify relevant English-language articles.
Study Selection: Randomized controlled trials evaluating ursodiol for the treatment of patients with cholesterol gallstones and chronic liver diseases were emphasized.
Data Synthesis: Ursodiol is at least as effective as chenodiol (chenodeoxycholic acid) for the dissolution of cholesterol gallstones and is associated with fewer adverse effects. Ursodiol desaturates bile, solubilizing cholesterol from the stone surface. The diameter of the largest stone is the most important determinant of successful dissolution. Dissolution with ursodiol is effective for approximately 30% to 50% of stones smaller than 20 mm in diameter, with the best results for small, buoyant stones. A meta-analysis of randomized trials with ursodiol found that the dissolution rate was 37% for patients treated with ursodiol at doses of more than 7 mg/kg per day or of more than 500 mg/d for at least 6 months. Maintenance therapy is effective for prevention of gallstone recurrence. Ursodiol also improves biochemical markers of cholestasis and inflammation when used to treat cholestatic liver diseases. By displacing potentially hepatotoxic bile salts, it appears to interrupt the cycle of cholestatic injury. It may also exert hepatoprotective membrane-stabilizing or immunomodulatory effects (or both). Improvements in laboratory variables are limited to the treatment period, with relapses after withdrawal of therapy. Pruritus may be markedly relieved in individual patients treated with ursodiol.
Conclusions: Ursodiol is a safe and effective therapy for the treatment of patients with cholesterol gallstones. Although treatment with ursodiol leads to improvement in biochemical markers for cholestatic liver diseases, whether it alters the natural history of these disorders is the subject of ongoing trials.