Ursodeoxycholic acid (UDCA) prophylaxis may reduce the occurrence of symptomatic gallstone disease among patients who did not have gallstones prior to undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. These findings were published in the Lancet Gastroenterology and Hepatology.
The Ursodeoxycholic Acid for the Prevention of Symptomatic Gallstone Disease after Bariatric Surgery (UPGRADE) trial was a multicenter, double-blind, randomized, placebo-controlled superiority trial. Patients undergoing RYGB or sleeve gastrectomy were recruited at 3 centers in the Netherlands between 2017 and 2018. Patients were randomly assigned in a 1:1 ratio to receive 900 mg UDCA (n=477) or placebo (n=490) daily for 6 months. Instance of symptomatic gallstone disease was assessed up to 24 months.
The UDCA and placebo cohorts were aged mean 45.5 (SD, 11.2) and 44.7 (SD, 11.0) years, 80% and 80% were women, body mass index (BMI) was 40.1 (SD, 4.8) and 40.2 (SD, 4.7) kg/m2, 48% and 50% had hypertension, 30% and 33% had dyslipidemia, 13% and 19% had type 2 diabetes, 20% and 19% had asymptomatic gallstones, and 92% and 92% underwent RYGB, respectively.
The average weight loss among all study participants was 23.0% at 6 months, 29.5% at 12 months, and 29.4% at 24 months.
Symptomatic gallstone disease by 24 months occurred among 6.5% of the UDCA and 9.7% of the placebo recipients (relative risk [RR], 0.67; 95% CI, 0.43-1.04; P =.071).
A significant interaction was observed for the presence of asymptomatic gallstones at baseline (adjusted odds ratio [aOR], 2.83; 95% CI, 1.02-7.86; P =.046).
Among patients without gallstones at baseline, symptomatic gallstone disease occurred among 4.2% of the UDCA and 8.9% of the placebo recipients (RR, 0.47; 95% CI, 0.26-0.84; P =.0081). For those with baseline gallstones, the occurrence of symptomatic disease by 24 months was 16.0% and 13.0% (RR, 1.22; 95% CI, 0.61-2.47; P =.57), respectively.
The protective effect of UDCA for patients without asymptomatic gallstones was only observed for RYGB (RR, 0.61; 95% CI, 0.38-0.98; P =.039) but not sleeve gastrectomy (RR, 1.32; 95% CI, 0.38-4.54; P =.66).
Cholecystectomy by 24 months occurred among 5.3% of the UDCA and 9.1% of the placebo cohorts (RR, 0.58; 95% CI, 0.36-0.93; P =.022).
UDCA and placebo recipients reported diarrhea (0.9% vs 0.4%) and skin rash (0.5% vs 0.4%, respectively). Serious adverse events such as abdominal pain and internal hernia occurred among 17% of the UDCA and 23% of the placebo cohorts.
Investigators acknowledge study was underpowered to detect significant effects for sleeve gastrectomy.
The study authors concluded that UDCA prophylaxis may be effective at preventing symptomatic gallstone disease among patients without gallstones undergoing RYGB.
Haal S, Guman MSS, Boerlage TCC, et al. Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial. Lancet Gastroenterol Hepatol. 2021;6(12):993-1001. doi:10.1016/S2468-1253(21)00301-0