Ursodeoxycholic Acid May Prevent Gallstones After Gastrectomy

By Marilynn Larkin

June 29, 2020

NEW YORK (Reuters Health) - Ursodeoxycholic acid (UDCA) reduced gallstone formation after gastrectomy in a randomized, controlled study in Korea.

Dr. Do Joong Park of Seoul National University randomized 521 patients to 300 mg UDCA, 600 mg UDCA or placebo after total, distal or proximal gastrectomy. Gallstone formation was assessed with abdominal ultrasonography every three months for one year post-surgery.

As reported in JAMA Surgery, the full analysis dataset included 465 patients (median age 50; 69% men). The proportion of patients developing gallstones within 12 months after gastrectomy was 5.3% in the 300-mg group, 4.3% in the 600-mg group, and 16.7% in the placebo group.

Compared with placebo, odds ratios for gallstone formation were 0.27 for 300 mg UDCA and 0.20 for 600 mg.

No significant adverse drug reactions were detected. The most common adverse reaction was nausea, followed by skin rash. Two patients died during the study - one in the 600 mg group and the other in the placebo group. Both deaths were associated with cancer recurrence.

The authors conclude, "These findings suggest that UDCA administration prevents gallstone formation after gastrectomy in patients with gastric cancer."

Limitations included a small sample size and short study period.

Dr. Henry Pitt of Temple University in Philadelphia, coauthor of a related editorial, told Reuters Health by email, "Vagotomy and gastrectomy for ulcer disease and gastric bypass for obesity are known to alter biliary physiology and promote gallstone formation. The efficacy of UDCA to prevent gallstones after these operations has been known for 25 years."

The current study is unique, he said, "because the surgery was performed for gastric cancer. The fact that UDCA prevented gallstones was not surprising, but the question of how long to continue treatment was not adequately studied. Also, the generalizability to Western patients undergoing gastrectomy for cancer is unclear."

"Thus," he said, "further studies in Western patients, while difficult to perform, would be ideal."

Dr. Jennifer Higa, a gastroenterologist at Fox Chase Cancer Center, also in Philadelphia, commented in an email to Reuters Health, "Gastroenterologists, as well as surgeons, commonly use UDCA for symptomatic cholelithiasis but not in a prophylactic manner, as this paper is suggesting."

"Not all patients who develop cholelithiasis will develop complications of this condition (e.g., cholecystitis, choledocholithiasis), and we do not have a way of risk stratifying which of the gastrectomy patients might develop gallstones plus complications," she noted.

"As such, I would find it potentially challenging to advocate empiric medication use for all gastrectomy patients for prevention of gallstone formation, both for cost reasons and potential lifelong use," she said.

"Since gastroenterologists do not perform cholecystectomy, but rather help to address the complications of cholelithiasis, a commonly held opinion is that prophylactic cholecystectomy (if feasible) at time of the operation - whether it be gastrectomy or bariatric surgery - is the most conservative approach."

Indeed, Dr. Pitt notes in his editorial that while "the recommendations of the authors of the current study to give UDCA to gastric cancer (patients) is appropriate...recommending a cholecystectomy for patients with a good cancer prognosis is another viable option."

Dr. Joong did not respond to requests for a comment.

The study was funded by Daewoong Pharmaceutical Co Ltd. Dr. Park and two coauthors received fees from the company.

SOURCE: https://bit.ly/2YCBfjb and https://bit.ly/2Ny0XyA JAMA Surgery, online June 17, 2020.