Experience of using ursodeoxycholic acid to dissolve gallstones

Objective of the study. A 5-year prospective study was aimed to evaluate the efficacy of Ursosan treatment for dissolving gallstones.

Material and methods. Patients who had single gallbladder stones were randomized to group A, in which 47 people completed the study (16 men and 31 women, median age is 67.6 years), and group B – 41 people 14 men and 27 women, median age is 68, 1 years). All patients of group A continuously received continuous treatment with ursodeoxycholic acid drug Ursosan at a dose of 10 mg /kg per day for 5 years. The patients of group D did not receive Ursosan; these individuals received periodic courses of spasmodic drugs. The patients passed clinical examination, laboratory tests, transabdominal ultrasound of the liver and biliary tract before the study, 2 times a year for 5 years and after the study.

Results. After 5 years of treatment, stones were detected in 10.6% of patients in group A. In group B, the incidence of gallstones did not change after 5 years of treatment, that is, calculi were detected in all patients (p <0.001). At the end of the study, no muldoi tiple stones were observed in any of the patients of group A, while multiple stones were detected in 2/3 of group B patients after 5 years of treatment. A distinct decrease in pain syndrome frequency and improvement in contractile function of the gallbladder were recorded in patients of group A as compared to the patients of group B by the end of the observation period. The side effect profile did not differ in groups A and B. The study showed good tolerance of Ursosan for 5 years of continuous administration of the drug.

Findings. The 5-year prospective study showed that Ursosan’s efficacy in dissolving gallstones accounted for 90%. Ursosan also prevented the formation of new calculi and reduced the frequency of pain, improved the gall-bladder contractile function and reduced the need for cholecystectomy by the end of the observation period.

1. Baiu I., Hawn M.T. Choledocholithiasis. JAMA. 2018;320(14):1506. doi: 10.1001/jama.2018.11812.

2. Zheng Y., Xu M., Heianza Y., Ma W., Wang T., Sun D., Albert C.M., Hu F.B., Rexrode K.M., Manson J.E., Qi L. Gallstone disease and increased risk of mortality: Two large prospective studies in US men and women. J Gastroenterol Hepatol. 2018;33(11):1925-1931. doi: 10.1111/jgh.14264.

3. Nassar Y., Richter S. Management of complicated gallstones in the elderly: comparing surgical and non-surgical treatment options. Gastroenterol Rep (Oxf). 2019;7(3):205-211. doi: 10.1093/gastro/goy046.

4. Portincasa P., Ciaula A.D., Bonfrate L., Wang D.Q. Therapy of gallstone disease: What it was, what it is, what it will be. World J Gastrointest Pharmacol Ther. 2012,3(2):7-20. doi: 10.4292/wjgpt.v3.i2.7.

5. Tomida S., Abei M., Yamaguchi T., Matsuzaki Y., Shoda J., Tanaka N., Osuga T. Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a cohort analysis. Hepatology. 1999;30(1):6-13. doi: 10.1002/hep.510300108.

6. Guarino M.P., Cong P., Cicala M., Alloni R., Carotti S., Behar J. Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones. Gut. 2007;56(6):815-820. doi: 10.1136/gut.2006.109934.

7. Chen X., Yan X.R., Zhang L.P. Ursodeoxycholic acid after common bile duct stones removal for prevention of recurrence: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018;97(45): e13086. doi: 10.1097/MD.0000000000013086.

8. Nabil T.M., Khalil A.H., Gamal K. Effect of oral ursodeoxycholic acid on cholelithiasis following laparoscopic sleeve gastrectomy for morbid obesity. Surg Obes Relat Dis. 2019;15(6):827-831. doi: 10.1016/j.soard.2019.03.028.

9. Della Penna A., Lange J., Hilbert J., Archid R., Königsrainer A., Quante M. Ursodeoxycholic Acid for 6 Months After Bariatric Surgery Is Impacting Gallstone Associated Morbidity in Patients with Preoperative Asymptomatic Gallstones. Obes Surg. 2019;29(4):1216-1221. doi: 10.1007/s11695-018-03651-0.

10. Dosch A.R., Imagawa D.K., Jutric Z. Bile Metabolism and Lithogenesis: An Update. Surg Clin North Am. 2019;99(2):215-229. doi: 10.1016/j.suc.2018.12.003.

11. Tsukanov V.V., Seliverstova Е.V., Dogadin S.A. Lipid composition of blood serum and bile in biliary diseases in patients with diabetes mellitus. Terapevticheskiy arkhiv = Therapeutic Archive. 2005;77(2):15-18. (In Russ.) Available at: https://elibrary.ru/item.asp?id=9133822.

12. Tsukanov V.V., Tonkikh Yu.L., Bronnikova E.P., Manchuk V.T. The mechanism of normolipidemia in northerners. Klinicheskaya meditsina = Clinical Medicine. 1999;77(2):38-39. (In Russ.)

13. Di Ciaula A., Wang D.Q., Portincasa P. Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention. Expert Rev Gastroenterol Hepatol. 2019;13(2):157-171. doi: 10.1080/17474124.2019.1549988.

14. Zhang Y., Jiang R., Zheng X., Lei S., Huang F., Xie G., Kwee S., Yu H., Farrar C., Sun B, Zhao A., Jia W. Ursodeoxycholic acid accelerates bile acid enterohepatic circulation. Br J Pharmacol. 2019;176(16):2848-2863. doi: 10.1111/bph.14705.

15. Simental-Mendía L.E., Simental-Mendía M., Sánchez-García A., Banach M., Serban M.C., Cicero A.F.G., Sahebkar A. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Lipids Health Dis. 2019;18(1):88. doi: 10.1186/s12944-019-1041-4.

16. Kim D.J., Chung H., Ji S.C., Lee S., Yu K.S., Jang I.J., Cho J.Y. Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways. Metabolomics. 2019;15(3):30. doi: 10.1007/s11306-019-1494-5.

17. Liu T., Song X., Khan S., Li Y., Guo Z., Li C., Wang S., Dong W., Liu W., Wang B., Cao H. The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing. Int J Cancer. 2019. doi: 10.1002/ijc.32563.

18. Pearson T., Caporaso J.G., Yellowhair M., Bokulich N.A., Padi M., Roe D.J., Wertheim B.C., Linhart M., Martinez J.A., Bilagody C., Hornstra H., Alberts D.S., Lance P., Thompson P.A. Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Med. 2019;8(2):617-628. doi: 10.1002/cam4.1965.

19. Goossens J.F., Bailly C. Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy. Pharmacol Ther. 2019;203:107396. doi: 10.1016/j.pharmthera.2019.107396.

20. Maevskaya M.V., Ivashkin V.T., Ivashkin K.V., Lunkov V.D., Liusina E.O., Zozula V.N., Leshchenko V.I. Non-alcoholic fatty liver disease as a cause and consequence of cardio- metabolic complications. Role of the ursodeoxicholic acid in the pharmacotherapy. Terapevticheskiy arkhiv = Therapeutic Archive. 2019;91(2):109-117. doi: 10.26442/00403660.2019.02.000122.

21. Chappell L.C., Bell J.L., Smith A., Linsell L., Juszczak E., Dixon P.H., Chambers J., Hunter R., Dorling J., Williamson C., Thornton J.G.; PITCHES study group. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019;394(10201):849-860. doi: 10.1016/S0140-6736(19)31270-X.

22. Goet J.C., Hirschfield G.M. Guideline review: British Society of Gastroenterology/UK-PBC Primary Biliary Cholangitis treatment and management guidelines. Frontline Gastroenterol. 2019;10(3):316-319. doi: 10.1136/flgastro-2018-101109.

23. Örnolfsson K.T., Lund S.H., Olafsson S., Bergmann O.M., Björnsson E.S. Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study. Scand J Gastroenterol. 2019;54(5):609-616. doi: 10.1080/00365521.2019.1606931.