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.