The Sunnybrook Gallstone Study: A Double–Blind Controlled Trial of Chenodeoxycholic Acid for Gallstone Dissolution

Abstract

The Sunnybrook Gallstone Study was a randomized, double-blind, controlled trial of chenodeoxycholic acid treatment over 2 years in 160 patients with radiolucent gallstones. Sixty-four patients received 750 mg daily, 53 received 375 mg daily and 43 received placebo. Total dissolution of gallstones occurred in 10.9% of patients on 750 mg daily, 13.2% of those on 375 mg daily and in no patient on placebo. The drug was tolerated well. Diarrhea severe enough to cause withdrawal from the study occurred in two patients. No patient developed clinically significant hepatotoxicity. Serum cholesterol rose 10% or more above baseline after 2 years in 33% of patients treated with chenodeoxycholic acid and in 30% of those on placebo. Cholecystectomy was performed in 10.9% of patients on 750 mg daily, 17% on 375 mg daily and 13.6% on placebo. Chenodeoxycholic acid given at these doses dissolved radiolucent gallstones safely but the efficacy was limited.

Cholecystolithiasis: Lithotherapy for the 1990S

“…In a recent series of 126 patients treated with ursodeoxycholic acid (8 to 10 *day), cystic duct obstruction developed in about 10% of patients after 4 yr of treatment and cholecystectomy was performed in 17% of the patients within 18 mo of treatment because of recurrent pain, acute cholecystitis or pancreatitis (126). However, the controlled trial by the National Cooperative Gallstone Study Group seems to indicate that the incidence of such events after BAT is not different from that in a matched control group (119).Many case series detailing BAT'S ability to cure are available (118)(119)(120)(121)(122)(123)(124)(127)(128)(129)(130). The selection criteria used in these series may be classified as "superoptimal," optimal or acceptable ( are strictly limited to superoptimal criteria; thus data for such patients must be gathered from several sources (119-121,124).…”

“…One may determine that the cure rate in the added group of patients is still very reasonable at 53% (Fig. 2B).Many series have used broader selection criteria ( 119,120,129,130). The "acceptable" criteria are those usually cited as the ones applicable for symptomatic radiolucent gallstones.…”

Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: A cohort analysis

“…Bile acid therapy (BAT) using chenodeoxycholic acid [15][16][17] or ursodeoxycholic acid (UDCA) [18][19][20][21][22][23][24][25][26][27][28][29][30] has been widely performed as safe nonsurgical therapy of GS. In addition, several studies have suggested that BAT may inhibit GS-related symptoms, [21][22][23]31,32 independent of GS dissolution.…”

“…These reports have been received with some skepticism because of the variable effort to differentiate symptoms consistent with biliary colic or acute cholecystitis from other nonspecific symptoms. 25 On the other hand, the National Cooperative Gallstone Study 16 and another study 17 have demonstrated that chenodeoxycholic acid does decrease the nonspecific symptoms, but not the rates of biliary pain or conversion to surgery. The duration in these studies was short, and the indication criteria for conversion to surgery was not clear.…”

Bile acid transport and regulating functions in the human biliary epithelium

“…15,16 UDCA therapy is also effective in the treatment of cholelithiasis 17 and in preventing biliary pain and acute cholecystitis in patients with gallstones, 18 whereas chenodeoxycholic acid treatment is not. 19 The therapeutic efficacy of UDCA has been attributed to a number of mechanisms 20 including the stimulation of canalicular bile acid secretion in cholestatic patients, 21 immunomodulatory 22 and anti-inflammatory properties, 23 anti-apoptotic effects, 24,25 and a reduction of the nucleation-promoting activity in bile. 23,26 The therapeutic efficacy of UDCA remains, however, incompletely understood, and yet another mechanism that has been hypothesized is that UDCA may act on biliary epithelial cells directly and affect their secretory functions.…”