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Prophylaxis against Gallstone Formation with Ursodeoxycholic Acid in Patients Participating in a Very-Low-Calorie Diet Program

Mitchell L. Shiffman, MD; Gordon D. Kaplan, PhD; Valerie Brinkman-Kaplan, MS, RD; and Florence F. Vickers*, PhD
[+] Article, Author, and Disclosure Information

From the Medical College of Virginia, Richmond, Virginia. Health Management Resources, Boston, Massachusetts. Ciba-Geigy Pharmaceutical Company, Summit, New Jersey. Requests for Reprints: Mitchell L. Shiffman, MD, Hepatology Section, Medical College of Virginia, P.O. Box 980711, Richmond, VA 23298-0711. Note: During the course of this study, Dr. Shiffman was a paid consultant to Ciba-Geigy Pharmaceutical Company, Dr. Vickers was Associate Director and then Director of Research and Development for Ciba-Geigy, and Dr. Kaplan and Ms. Brinkman-Kaplan were employees of Health Management Resources. Acknowledgments: The authors thank Larry T.P. Stifler, PhD, of Health Management Resources, Inc., for support and assistance; Kathleen Crotty of Ciba-Geigy Corporation for supervising the preparation of our statistical report; and Sherri Holmes and Jennifer Coady for technical assistance with the bile analysis. Grant Support: By Ciba-Geigy Pharmaceutical Company and the National Institutes of Health first award DK43264 from the National Institutes of Digestive and Kidney Diseases.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(12):899-905. doi:10.7326/0003-4819-122-12-199506150-00002
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Objective: To determine whether prophylactic treatment with ursodeoxycholic acid can prevent gallstone formation in persons participating in a very-low-calorie weight reduction diet program.

Design: Multicenter, double-blind, placebo-controlled, multidose clinical trial. Patients were treated with placebo or with 300 mg/d, 600 mg/d, or 1200 mg/d of ursodeoxycholic acid.

Setting: 31 Health Management Resources weight management centers.

Patients: 1004 patients were initially enrolled in a 16-week, 520-kcal/d, Health Management Resources liquid protein diet program. All patients had a body mass index of 38 kg/m2 or more and a normal gallbladder ultrasonogram before study entry. Bile analysis was done in 32 patients.

Measurements: Body weight and body mass index were measured before the diet was started and at 2-week intervals for 16 weeks. Gallbladder ultrasonography was done before enrollment and after 8 and 16 weeks of dieting. Bile was obtained by endoscopy and analyzed for cholesterol crystals and lipid levels.

Results: Mean body weight for all patients at the start of dieting was 128.2 kg ±23.2 kg; mean initial body mass index was 44.2 kg/m2 ±6.0 kg/m2. Gallstones developed in 28% (95% CI, 22% to 35%) of patients receiving placebo, in 8% (CI, 5% to 13%) of patients treated with 300 mg/d of ursodeoxycholic acid, in 3% (CI, 1% to 7%) of patients treated with 600 mg/d of ursodeoxycholic acid, and in 2% (CI, 0.5% to 5%) of patients treated with 1200 mg/d of ursodeoxycholic acid. The differences between patients receiving placebo and patients receiving ursodeoxycholic acid were statistically significant. The percentage of ursodeoxycholic acid in bile increased stepwise with increasing doses of ursodeoxycholic acid.

Conclusions: Ursodeoxycholic acid, 600 mg/d, is highly effective in preventing gallstone formation in patients having dietary-induced weight reduction.

For a listing of additional persons involved in the conduct of this study, see Appendix.


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Figure 1.
Percentage of patients who developed gallstones during the diet program.

The fractions above each bar indicate the number of patients who developed gallstones in each group over the total number of patients in each group. Solid bars represent men; open bars represent women. Values for all doses of ursodeoxycholic acid in both men and women were significantly lower than those for placebo. For women, values for the 600 mg/d dose of ursodeoxycholic acid were significantly lower than those for the 300 mg/d dose. UDCA = ursodeoxycholic acid.

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Figure 2.
Weight loss, body mass, and gallstone formation.Top.Bottom.

Fractions above each bar indicate the number of patients who developed gallstones in each group over the total number of patients in each group. Solid bars represent men; open bars represent women. Relation between the rate of weight loss and gallstone formation in patients treated with placebo. The stepwise increase seen in women was significant. No significant relation between rate of weight loss and gallstone formation was present in men. Relation between the percentage decrease in body mass index and gallstone formation in patients treated with placebo. BMI = body mass index.

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