Ursodeoxycholic Acid May Prevent Post-Gastrectomy Gallstones

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The PEGASUS-D study has demonstrated a reduced risk of gallstone formation for Korean gastric cancer patients who are given ursodeoxycholic acid (UDCA) for 1 year after gastrectomy compared with use of placebo. 

“Although it is difficult to make any definitive conclusions, we suggest that gallstone formation and its complications may be prevented by use of UDCA rather than prophylactic cholecystectomy”, suggest Do Joong Park, from Seoul National University College of Medicine in South Korea, and co-authors in JAMA Surgery.

The primary endpoint of gallstone diagnosis within 12 months of total, distal or proximal gastrectomy occurred in 5.3% of the 151 patients given UDCA 300 mg/day, 4.3% of the 164 patients given UDCA 600 mg/day and 16.7% of the 150 patients given placebo. 

Both the 300 mg/day and 600 mg/day UDCA doses significantly reduced the risk of gallstone formation at this time compared with placebo, with odds ratios of 0.27 and 0.20, respectively, report the investigators.

“The preventative effects of UDCA on gallstone formation were observed 3 months after administration”, they continue, citing per protocol rates at 3, 6 and 9 months for the 300 mg/day group (0.0, 1.7 and 2.6%, respectively), 600 mg/day group (0.8, 0.8 and 1.6%) and placebo arm (7.1, 9.8 and 12.5%).

Safety analysis of the 516 patients who received at least one study dose showed no significant difference in the rate of adverse drug reactions between the three groups. The most common events were nausea (0.8%) and rash (0.6%), and both deaths in the study were attributed to cancer recurrence.

“In the future, studies comprising a larger number of patients with long-term follow-up are needed to confirm whether the use of UDCA can reduce the number of patients undergoing subsequent cholecystectomy”, the researchers conclude.

The authors of an accompanying commentary observe that when UDCA therapy was stopped at 12 months the incidence of gallstones “rapidly increased” from 5% to 10% among the UDCA 300 mg/day treatment group and from 17% to 35% among controls.

“Unfortunately, this aspect of the study was not completely reported but suggests that follow-up for more than 1 year is important and that UDCA prophylaxis should not be stopped at 1 year,” write Henry Pitt, from Temple University in Philadelphia, Pennsylvania, USA and Attila Nakeeb, from Indiana University in Indianapolis, USA.

Highlighting the absence of demographic information on the patients who developed gallstones, the commentators also question the “generalizability” of the study to Western patients, who are more likely than the Korean study participants to be female, overweight and have advanced gastric cancer, as well as other differing factors. 

But acknowledging the difficulties of repeating the study in a Western patient cohort, the commentators believe “the authors’ recommendations to give UDCA to prevent gallstones in patients undergoing gastrectomy for gastric cancer is appropriate”. 

“However, recommending a cholecystectomy for patients with a good cancer prognosis is another viable option”, state Henry Pitt and Attila Nakeeb. 

References 

Lee SH, Jang DK, Yoo M-W, et al. Efficacy and safety of ursodeoxycholic acid for the prevention of gallstone formation after gastrectomy in patients with gastric cancer. The PEGASUS-D randomized clinical trial. JAMA Surg; Advance online publication 17 June 2020. doi:10.1001/jamasurg.2020.1501

Pitt HA, Nakeeb A. Prevention of gallstone formation after gastrectomy. doi:10.1001/jamasurg.2020.1527