Combinatorial Effects of Terpene, Chenodeoxycholic Acid, and Ursodeoxycholic Acid on Common Bile Duct Stone Recurrence and Gallbladder Stone Dissolution

Abstract

Background: Ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA) plus UDCA (C&U), and terpene are widely administered to prevent common bile duct (CBD) stone recurrence and dissolve gallbladder (GB) stones. We evaluated and compared the combined effects of these agents on CBD stone recurrence and GB stone resolution. Methods: This study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) at six referral centers, retrospectively. A total of 940 patients who underwent cholecystectomy before or after CBD stone removal by ERCP were evaluated to assess CBD stone recurrence (the CBD recurrence cohort), and 98 patients with GB stones were assessed by abdominal or endoscopic ultrasonography before and 6 months after ERCP to evaluate GB stone resolution (GB cohort). Patients were divided into no-medication, single-agent treatment (UDCA, C&U, or terpene), or dual-agent treatment (terpene plus UDCA or C&U) groups for the analysis. Results: In the CBD recurrence cohort, baseline characteristics were similar in the three groups. CBD stone recurrence rates were 41.5%, 12.7%, and 9.8% in the no-medication, single-agent, and dual-agent groups, respectively (p < 0.001), and the recurrence rate was significantly lower for those administered C&U plus terpene (5.2% vs. 13.2%, p = 0.002). In the GB cohort, baseline characteristics were also similar in the groups. GB stone resolution rates of >30% were observed in 5.3%, 14.3%, and 34.8% of patients in the no-medication, single-agent, and dual-agent groups, respectively (p = 0.028). Conclusions: C&U plus terpene was significantly more effective for preventing CBD stone recurrence and achieving GB stone resolution than no medication or single agents.