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Gallstone Dissolving Therapy

Patient Information

Gallstone Dissolving Therapy

While the only effective treatment for most patients with symptomatic gall stones is surgical removal of the gall bladder, there are many patients who can avoid gall bladder surgery by using medication to dissolve their gallstones. Gallstone dissolving medication has been shown to effectively dissolve cholesterol gallstones by solubilising cholesterol in bile and has a success rate of 30 – 50% for completely dissolving gall stones.

Patients suitable for gallstone dissolving therapy at our clinic have:

  1. Cholesterol Gallstones
    1. Must be <10mm in size
    2. Must not be calcified as proven by CT scan
  2. Recurrent pancreatitis from biliary sludge or microlithiasis (microscopic stones)
  3. Post cholecystectomy pain from sludge or microlithiasis (microscopic stones)

Cholelithiasis

UDCA is a hydrophilic bile salt medication that has the power to dissolve cholesterol gall stones. The mechanism of action for UDCA is multifactorial. First, UDCA is hydrophilic whereas many other bile acids are hydrophobic and therefore more cytotoxic to hepatocytes. The UDCA competes with dominant endogenous bile acids for absorption in the terminal ileum, making the bile acid pool more hydrophilic.2,3 Second, UDCA has a direct protective effect on hepatocytes against bile acid-induced apoptosis.3 Third, in cholestatic diseases, the retention of toxic bile acids leads to cell injury. The UDCA counters this effect by stimulating hepatocytes and bile duct epithelial cells to secrete bile.4 The UDCA is generally a well- tolerated drug, but weight gain is a well-documented side effect. Patients gain on average 2.2 kg in the first year of treatment and their weight stabilizes thereafter.5

Cholecystectomy (surgical gall bladder removal) is the treatment of choice for patients with symptomatic gall stones. However, in certain cases of uncomplicated cholelithiasis, UDCA may be used to dissolve gall stones. The UDCA is useful in longer-term treatment of gallstones in patients not undergoing cholecystectomy. In a nonrandomized cohort of 527 patients with uncomplicated gallstones, UDCA was associated with decreased need for cholecystectomy and decreased biliary pain. This was independent of the analysis of gallstone dissolution.35 Among patients with an intact gallbladder, recurrent acute pancreatitis may occur less frequently when UDCA is used, especially if microlithiasis may be playing a role.36 In patients with recurrent pancreatitis who will not undergo cholecystectomy, performing a sphincterotomy is advised as well.37

In certain populations, UDCA may effectively dissolve cholesterol gallstones by solubilizing cholesterol in bile. A meta-analysis showed that UDCA successfully dissolved radiolucent stones in 37% of patients. The efficacy increased with decreasing size of the stones.38 Other analyses have shown dissolution rates of 30%-50%.39 However, stones frequently return after dissolution with UDCA. Single stones have the lowest rate of recurrence.40,41 Recurrence rates have been shown to be 12.5% in the first year and 61% by 11 years in one study.41

Patient selection is very important for successful dissolution of gallstones with UDCA. Ideal candidates for UDCA therapy should have a functioning gallbladder, their largest stone should be ideally less than 5 mm and certainly less than 10 mm, and the stones should be of the cholesterol variety and thus radiolucent.35,42,43 
Ursodeoxycholic acid has been shown to reduce the incidence of rapid weight loss induced gallstone formation in patients undergoing gastric bypass. A randomized placebo- controlled study using 600 mg daily for 6 months reduced the incidence of gallstone formation over 6 years following gastric bypass from 32% with placebo to 2% with UDCA.44

Microlithiasis

Treatment of microlithiasis may include cholecystectomy, endoscopic sphincterotomy, or UDCA. The UDCA can prevent recurrence of acute ‘‘idiopathic’’ pancreatitis, which is often caused by biliary sludge and microlithiasis in patients with an intact gallbladder.36,45In a study of patients with recurrent pancreatitis and cholesterol monohydrate crystals in their bile, UDCA eliminated biliary microlithiasis and pre- vented recurrence of pancreatitis over a 44-month period.36 In another small study, 4 out of 5 patients with biliary sludge and microlithiasis treated with UDCA achieved long-term relief from recurrent pancreatitis.45,46 Because of the risk of recurrence, however, cholecystectomy is routinely recommended in patients with biliary sludge who have had acute pancreatitis.

Many patients who undergo cholecystectomy for sympto- matic gallstones continue to experience pain. Approximately one-third of all patients undergoing cholecystectomy will experience this postcholecystectomy syndrome. The patho- physiology of postcholecystectomy syndrome has not been clearly delineated, though several mechanisms have been proposed including sphincter of Oddi dysfunction.47

Microlithiasis has been identified in some patients who have undergone cholecystectomy, and one study demonstrates that it may be a cause of postcholecystectomy pain. The UDCA may be useful for treatment in these cases. The study looked at 118 patients with postcholecystectomy syndrome, and 12 (10%) were found to have microlithiasis on examination of their bile. These 12 patients were further studied. In the first phase of the study, 6 patients received UDCA and had a significant reduction in pain compared to the untreated 6 patients. In the second phase, the other 6 patients were treated with UDCA and also experienced a significant reduction in pain. The UDCA may be of benefit in patients with postcholecystectomy pain and microlithiasis.47

This study was limited by several factors including the small sample size of 12 and the lack of placebo control. Bile analysis was not performed after treatment to confirm the resolution of microlithiasis as the reason for pain relief. Also, the appropriate duration of treatment is not known. It is not known whether endoscopic sphincterotomy is an effective therapy in patients with microlithiasis and postcholecystect-47 omy syndrome.

Endnotes

  1. Lindor K. Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. N Engl J Med. 2007;357:1524-1529.

  2. Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited [review]. Hepatology. 2002;36(3):525 – 531.

  3. Perez MJ, Briz O. Bile-acid-induced cell injury and protection [review]. World J Gastroenterol. 2009;15(14):1677-1689.

  4. Siegel JL, Jorgensen R, Angulo P, et al. Treatment with ursodeoxycholic acid is associated with weight gain in patients with primary biliary cirrhosis. J Clin Gastroenterol. 2003;37(2):183 -185.

  1. Tomida S, Abei M, Yamaguchi T, et al. 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;30:6-13.

  2. Ros E, Navarro S, Bru C, et al. Occult microlithiasis in ‘idiopathic’ acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxy- cholic acid therapy. Gastroenterology. 1991;101(6):1701-1709.

  3. Van Geenen E, van der Peet D, Mulder C, et al. Recurrent acute biliary pancreatitis: the protective role of cholecystectomy and endoscopic sphincterotomy. Surg Endosc. 2009;23:950-956.

  4. May GR, Sutherland LR, Shaffer EA. Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials. Aliment Pharmacol Ther. 1993;7(2):139-148.

  5. Rubin RA, Kowalski TE, Khandelwal M, et al. Ursodiol for hepatobiliary disorders. Ann Intern Med. 1994;121(3):207-218.

  6. Petroni ML, Jazrawi RP, Pazzi P, et al. Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group. Eur J Gastroenterol Hepatol. 2000;12(6):695-700.

  7. Villanova N, Bazzoli F, Taroni F, et al. Gallstone recurrence after successful oral bile acid treatment. A 12-year follow-up study and evaluation of long-term postdissolution treatment. Gastroenterology. 1989;97(3):726-731.

  8. Fromm H, Malavolti M. Bile acid dissolution therapy of gallbladder stones. Baillieres Clin Gastroenterol. 1992;6(4):689-695.

  9. Caroli A, Del Favero G, Di Mario F, et al. Computed tomography in predicting gall stone solubility: a prospective trial. Gut. 1992;33(5):698-700.

  10. Sugerman HJ, Brewer WH, Shiffman ML, et al. A multicenter, placebo- controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric- bypass-induced rapid weight loss. Am J Surg. 1995;169(1):91-96; discus- sion 96-97.

  11. Saraswat VA, Sharma BC, Agarwal DK, et al. Biliary microlithiasis in patients with idiopathic acute pancreatitis and unexplained biliary pain: response to therapy. J Gastroenterol Hepatol. 2004;19(10):1206-1211.

  12. Testoni PA, Caporuscio S, Bagnolo F, et al. Idiopathic recurrent pancreatitis: long-term results after ERCP, endoscopic sphincterotomy, or ursodeoxycholic acid treatment. Am J Gastroenterol. 2000;95(7):1702- 1707.

  13. Okoro N, Patel A, Goldstein M, et al. Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis. Gastro- intest Endosc. 2008;68(1):69-74.

Review Paper

To read the full review see the medical paper below.


Gallstone Dissolving Therapy, Review Article