Prevention And Treatment Of Gallstones

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Because ursodeoxycholic acid (UDCA) acts to decrease bile saturation it was investigated as an agent to preventing lithogenic changes in bile during weight loss. Aspirin was also studied as an agent which might inhibit nucleation and thereby reduce gallstone risk. Broomfield et al. (32) randomized 68 obese patients into placebo, UDCA (1200mg/day) and aspirin (1300mg/day) treatment groups. All participants consumed a low-calorie powdered food supplement (55 g protein, 79 g carbohydrate, 1g fat) amounting to 520kcal/day (2177kJ/day). Mean weight loss in the groups was between 21 and 25 kg over a period of 16 weeks. Follow-up ultrasound scans at 4 weeks and 19 weeks showed that UDCA successfully prevented formation of gallstones. The aspirin medication resulted in a lower but non-significant difference from placebo.

To investigate further the possible preventive effects of aspirin, Kurata et al. (33) examined data from 4524 patients in a randomized, controlled trial where half the patients received 1 g of aspirin per day. Hospitalization rates for gallstone disease were approximately equivalent to national rates and the usual associations of age, triglycerides, obesity and female gender were found. No effect was seen for aspirin medication. The authors conclude that a larger dose might be effective but because of aspirin's gastrointestinal side effects, its eventual utility is questionable.

In another study, Marks et al. (34) looked at effects of ursodiol or ibuprofen on gallbladder contractions and bile among obese patients during weight loss treatment. After a VLCD of 529 kcal/ day (2215 kJ/day) for 12 weeks, reduced contraction of the gallbladder, increased cholesterol saturation and increased nucleation and growth of cholesterol crystals were noted. However, no gallstones formed in any group. Ibuprofen treatment showed some promise in that it prevented an increase in saturation and reduction in gallbladder contraction and showed a trend opposing the increase in nucleation and growth of crystals.

A double-blind study of effectiveness of UDCA in preventing gallstone development after vertical band gastroplasty in 29 morbidly obese patients is reported by Worobetz et al. (35). Three months after surgery patients had lost a mean of 17% of pre operative weight. Six of 14 placebo patients versus none of 10 UDCA treated patients developed gallstones, suggesting that gallstone formation following gastroplasty can be prevented by UDCA therapy.

Sugerman et al. (31) investigated a 6-month regimen of prophylactic ursodiol to prevent development of gallstones after gastric bypass in patients with BMI of 40 or above before surgery. The study used three dose levels: placebo, and 300, 600 and 1200 mg daily. At 6 months, gallstone formation was noted in 32%, 13%, 2% and 6% respectively. The 600 and 1200 doses were significantly different from placebo. The authors conclude that a dose of 600 mg is an effective prophylactic in these patients.

In a multicenter, non-surgical study, Shiffman et al. (36) enrolled 1004 patients with BMI of 38 or greater into a 520 kcal/day (2177 kJ/day) liquid diet program. Subjects had ultrasound scans at the start and at 8 and 16 weeks. Again, subjects were randomized to placebo, 300, 600 or 1200mg/day of ursodeoxycholic acid. Gallstones developed in 28%, 8%, 3% and 2% of subjects, respectively, and differences between groups remained even after long-term follow-up, showing that UDCA could be an effective prophylactic during well-defined, high-risk periods.

The use of UDCA for dissolution of existing gallstones has also been investigated, with mixed results. Administration of UDCA in a dose of 8-10mg/kg/day leads to complete or partial gallstone dissolution in about 75% of cases. However, complications such as cystic duct obstruction and biliary pain may occur and only about 17% of cases achieved complete gallstone dissolution. (37).

Laparoscopic cholecystectomy is currently the preferred treatment for symptomatic gallbladder stones. Although it is more technically demanding in obese patients, the risks are comparable to those for non-obese patients and may be lower than with traditional surgical methods (38).

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