Comparative Efficacy and Side Effects of Ursodeoxycholic and Chenodeoxycholic Acids in Dissolving Gallstones

Abstract

In a double-blind controlled study of ursodeoxycholic acid (400 and 800 mg/day) and chenodeoxycholic acid (375 and 750 mg/day), in comparison with placebo, ursodeoxycholic acid was significantly more effective than chenodeoxycholic acid in dissolving gallstones after 12 mo of treatment. Although there continued to be better dissolution during ursodeoxycholic acid treatment (dissolution complete in 30% and partial in another 30% of the patients) than during chenodeoxycholic acid treatment (dissolution complete in 7% and partial in 40%) at 24 mo, this difference between the treatment groups was no longer statistically significant. The incidence of floating stones was significantly higher in the patients who dissolved their stones than in those who did not (p less than 0.001). The three failures of dissolution of floating stones during bile acid treatment were associated with chenodeoxycholic acid therapy--two of them with the 750-mg and the third with the 375-mg doses. Gallstone dissolution with ursodeoxycholic acid occurred in spite of a rise in biliary cholesterol saturation, which was consistent with a nonmicellar mechanism of cholelitholysis. Furthermore, more than threefold serum elevations of L-alanine aminotransferase were observed only during chenodeoxycholic acid therapy. They occurred in 2 patients treated with 375 and 750 mg/day, respectively. The enzyme levels normalized after discontinuation of chenodeoxycholic acid and have remained normal for 13 and 8 mo, respectively, after the institution of treatment with 800 mg/day of ursodeoxycholic acid. There was no correlation between the liver tests and biliary levels of lithocholic acid. Of all the symptoms studied, only constipation showed changes that approached statistical significance (p = 0.0681). There was a significant improvement of constipation in the combined chenodeoxycholic acid groups when they were compared with the combined ursodeoxycholic acid groups. The total bile acid pool expanded significantly in both the chenodeoxycholic acid and in the 800-mg ursodeoxycholic acid treatment groups. The marked increases of biliary ursodeoxycholic acid and chenodeoxycholic acid, respectively, indicated compliance with the treatment in all but 1 bile acid-treated patient. Neither serum triglycerides nor serum cholesterol showed significant changes in any of the treatment groups. The study shows that ursodeoxycholic acid dissolves gallstones faster and with fewer side effects than chenodeoxycholic acid. The results of the study are also consistent with the view that ursodeoxycholic acid is cholelitholytic at a lower dose than is chenodeoxycholic acid.