Medicinal Treatments of Cholesterol Gallstones: Old, Current and New Perspectives
P. Portincasa, Agostino Di Ciaula, Helen H. Wang, Antonio Moschetta and David Q.-H. Wang
Affiliation: Section of Internal Medicine, Dept. Internal and Public Medicine, University Medical School, Piazza Giulio Cesare 11, Policlinico, 70124 Bari, Italy.
Cholesterol cholelithiasis is one of the most common and costly digestive diseases. Although gallstones are usually asymptomatic and no treatment is generally required, it is imperative to treat symptomatic gallstones with or without complicated conditions. Laparoscopic cholecystectomy is first-line therapy for symptomatic gallstones. By contrast, a cautious study on the natural history of the disease and costs of therapy, indicates that non-surgical treatment of gallstones is currently restricted to a subgroup of patients with mild symptoms or with small radiolucent cholesterol gallstones in a functioning gallbladder. Appropriate selection of patients suitable for medical therapy is therefore of key importance. Oral litholysis with the hydrophilic bile acid ursodeoxycholic acid induces cholesterol desaturation of bile and may lead to gallstone dissolution in patients with small, radiolucent, cholesterol-enriched stones in a functioning gallbladder with a patent cystic duct. Recent studies from experimental animal models and preliminary findings in humans also suggest that blocking intestinal absorption of cholesterol with the powerful, specific, and effective NPC1L1 inhibitor ezetimibe, may offer a novel and exciting strategy for the treatment of cholesterol gallstones. A similar possibility might arise from manipulation of specific nuclear receptors involved in cholesterol and bile acid homeostasis. Current views and perspectives on medicinal treatment of cholesterol gallstone disease are discussed here.
Keywords: Dissolution therapy, bile salts, ezetimibe, intestine, gallbladder, bile, nuclear receptors
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