The Lancet Gastroenterology & Hepatology: Ursodeoxycholic acid can be used to prevent symptomatic gallstone disease after bariatric surgery

Ursodeoxycholic acid can dissolve gallstones, but this drug is only effective for cholesterol stones, and has no effect on melanin stones and bile pigment stones
.
In addition, rapid weight loss is the main risk factor for the formation of cholesterol gallstones
.
Therefore, morbidly obese patients undergoing bariatric surgery often suffer from symptomatic gallstone disease
.
This study aims to evaluate the efficacy of ursodeoxycholic acid compared with placebo in preventing symptomatic gallstone disease after bariatric surgery
.

This is a multicenter, double-blind, randomized, placebo-controlled trial involving patients with intact gallbladder who plan to undergo laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy
.
Patients were randomly assigned (1:1) to receive 900 mg of ursodeoxycholic acid per day or a matching placebo through the network randomization module for 6 months of treatment
.
Random assignment is stratified based on the presence of asymptomatic gallstones at baseline and the type of surgery
.
Patients, clinicians, and researchers keep the treatment allocation confidential
.
The main endpoint is whether the patient has cholelithiasis within 24 months
.
In addition, safety assessments were performed on all patients who took at least one dose of the study drug
.

From January 11, 2017 to October 22, 2018, 985 patients were randomly assigned to receive ursodeoxycholic acid (n=492) or placebo (n=493)
.
967 patients were included in the revised intention-to-treat population, of which 959 had data available for the primary endpoint assessment
.
189 (20%) patients had asymptomatic gallstones at baseline, and 78 (8%) underwent sleeve gastrectomy
.
Of the 475 patients in the ursodeoxycholic acid group, 31 (6.
5%) developed symptomatic gallstones, and of the 484 patients in the placebo group, 47 (9.
7%) developed symptomatic Cholelithiasis (HR:0-67, 95% CI 0.
43-1.
04, P=0.
071)
.
Logistic regression showed that there was a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0.
046), and ursodeoxycholic acid had an effect on patients without gallstones (HR: 0.
47, 95%) CI: 0.
27-0.
84, p=0.
0081), but had no effect on patients with asymptomatic gallstones at baseline (HR: 1.
22, 95% CI: 0.
61-2.
47, p=0.
57)
.
In patients without gallstones at baseline, the effect of receiving RYGB was stronger (HR: 0.
37, 95% CI: 0.
20-0.
71, p=0.
0016), while the subgroup of patients who underwent sleeve gastrectomy was too small to draw A clear conclusion
.
Adverse events are rare
.
In the ursodeoxycholic acid group, 4 out of 444 patients (0.
9%) had diarrhea, and 2 (0.
5%) patients had a rash
.
In the placebo group, 2 out of 453 patients (0.
4%) had diarrhea, and 2 (0.
4%) patients had a rash
.
There was no significant difference in the total number of serious adverse events between the trial groups (75 out of 444 patients in the ursodeoxycholic acid group [17%] and 102 out of 453 patients in the placebo group [23%])
.
The most common serious adverse events were abdominal pain and internal hernia
.

This study confirmed that the prevention of ursodeoxycholic acid did not significantly reduce the incidence of symptomatic gallstone disease in all patients after bariatric surgery
.
In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease
.
However, further research is needed to evaluate the efficacy of ursodeoxycholic acid after sleeve gastrectomy
.

Original source:

SylkeHaal.
Et al.
Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial.
The Lancet Gastroenterology & Hepatology.
2021.