Gallstones are one of the most common disorders in the western world and are found in 12% of the adult population. Rapid weight reduction is one of the most significant risk factors associated with gallstone formation. Approximately 25% of persons who lose weight through very-low-calorie diet programs [1] or gastric bypass surgery [2] will develop gallstones. Although I agree with Dr. Kaye that most stones that form during rapid weight reduction are initially asymptomatic, several large epidemiologic studies have shown that each year, 1% to 4% of persons with gallstones will develop biliary colic (15% to 25%, within 15 years); 40% to 50% of these patients will have recurrent biliary colic requiring cholecystectomy [3]. No data support the contention that gallstones developing after rapid weight loss have a different natural history.

Our recent studies [1, 2] clearly show that UDCA is extremely effective in preventing gallstone formation among patients undergoing rapid weight reduction. Of even greater importance, gallstone prevalence 1 year after cessation of weight loss was significantly lower in patients who had been treated with UDCA during the time of active weight reduction than in patients receiving placebo [2]. This finding suggests that the beneficial effects of short-term UDCA treatment during this high-risk period may be long lasting. Most persons who develop symptomatic gallstones do so many years after dieting has been completed. As such, the cost–benefit ratio of gallstone prophylaxis would not be favorable in a short-term analysis. If, however, a long-term follow-up can show that the incidence of gallstones in patients treated with UDCA during dieting remains low, then a substantial future medical cost savings could be realized.

Mendez-Sanchez and coworkers suggest that the cost–benefit ratio of UDCA prophylaxis could be improved if this agent were used only in patients who participate in diets with very low fat content. Dietary fat is a major stimulus for gallbladder contraction; however, the hypothesis that diets containing lower percentages of fat are associated with a greater risk for gallstone formation remains pure speculation. Until such information becomes available, it is probably better to use short-term UDCA treatment during active weight loss in all patients than to place patients at risk for gallstone formation and potential future complications. A previous analysis has shown that UDCA is a cost-effective treatment for gallstones [4]. Such an analysis should now be done for gallstone prophylaxis before our notions regarding this issue are set in "stone."

Mitchell Shiffman, MD

Medical College of Virginia

Richmond, VA 23298-0711