Medical Management of Cholesterol Gallstones

Abstract

Cholesterol gallstones are a significant cause of morbidity in the U.S. Methods used to treat gallstones include cholecystectomy or medical dissolution. The primary drugs used for the dissolution of cholesterol gallstones are two bile acids, chenodeoxycholic acid and ursodeoxycholic acid. Complete or partial gallstone dissolution rates using chenodeoxycholic acid have ranged from 30 to 80 percent. Factors affecting gallstone dissolution using the bile acids include the dosage and administration schedule, obesity, the stone characteristics, diet, and the duration of therapy. The adverse effects of chenodeoxycholic acid include gastrointestinal complaints, hepatotoxicity, and increased serum cholesterol. Ursodeoxycholic acid, which is investigational, differs from chenodeoxycholic acid in its mechanism of action. Ursodeoxycholic acid has similar efficacy with chenodeoxycholic acid, at a lower daily dosage, with less gastrointestinal and hepatic adverse effects. If appropriate patient selection is used, the response rate to medical therapy can range from 50 to 80 percent.

Inhibition of calcium oxalate precipitation by bile salts

“…However, the hypothetical therapeutic use of BA in stone-forming patients would present at least two major problems: these substances are known to be (i) hepatotoxic when used at high doses (which would be necessary to yield high urinary concentrations) for prolonged periods of time; 31 and (ii) lithogenic, like other calcium sequestrant agents which cause hyperoxaluria by increasing intestinal absorption of oxalate, 32 one of the major risk factors for calcium urolithiasis. 8 In conclusion, we found that BA inhibit calcium oxalate precipitation in vitro, a property that appears of interest from both a physiopathologic and pharmacologic point of view even if does not seem currently exploitable for prophylactic or therapeutic purposes.…”

“…However, the hypothetical therapeutic use of BA in stone‐forming patients would present at least two major problems: these substances are known to be (i) hepatotoxic when used at high doses (which would be necessary to yield high urinary concentrations) for prolonged periods of time; 31 and (ii) lithogenic, like other calcium sequestrant agents which cause hyperoxaluria by increasing intestinal absorption of oxalate, 32 one of the major risk factors for calcium urolithiasis 8 …”

Nonsurgical Treatment of Cholelithiasis: An Analysis of Clinical Opportunity

“…A decrease in the size of stones was achieved in 26.3%, 33.9%, and 17.0%, respectively. In addition, reducing dietary cholesterol may improve the efficacy of bile acid therapy (1).…”