Long-term efficacy of ursodeoxycholic acid for the prevention of gallstone formation after gastrectomy in patients with gastric cancer: a randomized clinical trial.

[BACKGROUND] The optimal long-term strategy for preventing post-gastrectomy gallstone formation in gastric cancer (GC) remains unclear. This study evaluated the sustained efficacy of a 12-month course of ursodeoxycholic acid (UDCA) after gastrectomy for GC.

[METHODS] We conducted a randomized, double-blind, placebo-controlled clinical trial at 13 institutions in the Republic of Korea. Patients who underwent total, distal, or proximal gastrectomy for GC were randomized 1:1:1 to receive either 300 mg UDCA, 600 mg UDCA, or placebo daily for 12 months. The primary outcome was the incidence of gallstone formation at least 5 years post-gastrectomy. Secondary outcomes were biliary pain, gallstone complications, and cholecystectomy.

[RESULTS] A total of 431 participants (300 mg UDCA: n = 141; 600 mg UDCA: n = 150; placebo: n = 140) were analyzed. At 80 months post-gastrectomy, gallstone formation occurred in 10.00% of the 300 mg group, 12.83% of the 600 mg group, and 26.21% of the placebo group. UDCA significantly reduced the hazard of gallstone formation compared to placebo (hazard ratio: 0.33, 95% CI 0.18-0.63, P = 0.0014 for 300 mg; 0.43, 95% CI 0.25-0.75, P = 0.0064 for 600 mg). There were no significant differences among groups in the incidence of biliary pain, gallstone complications, or cholecystectomy.

[CONCLUSION] Twelve months of UDCA administration was associated with sustained reduction in gallstone formation for up to 80 months after gastrectomy in GC patients.