Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol
Article first published online: 19 FEB 2013
© 2013 The Authors. European Journal of Clinical Investigation © 2013 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 43, Issue 4, pages 413–426, April 2013
How to Cite
Eur J Clin Invest 2013; 43 (4): 413–426
- Issue published online: 18 MAR 2013
- Article first published online: 19 FEB 2013
- Accepted manuscript online: 9 FEB 2013 09:51AM EST
- Manuscript Accepted: 22 JAN 2013
- Manuscript Received: 13 AUG 2012
- National Institutes of Health
- Saint Louis University Liver Center Seed Grant Award
- Saint Louis University President's Research Fund
- Ministero dell'Istruzione, dell'Università e della Ricerca. Grant Numbers: FIRB2003, RBAU01RANB002
- Fondazione Cassa di Risparmio di Puglia
- bile acid;
- bile flow;
- cholesterol crystallization;
- cholesterol monohydrate crystal;
Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors and represents a failure of biliary cholesterol homoeostasis in which the physical–chemical balance of cholesterol solubility in bile is disturbed.
The primary pathophysiologic event is persistent hepatic hypersecretion of biliary cholesterol, which has both hepatic and small intestinal components. The majority of the environmental factors are probably related to Western-type dietary habits, including excess cholesterol consumption.
Laparoscopic cholecystectomy, one of the most commonly performed surgical procedures in the United States, is nowadays a major treatment for gallstones. However, it is invasive and can cause surgical complications, and not all patients with symptomatic gallstones are candidates for surgery. The hydrophilic bile acid, ursodeoxycholic acid (UDCA), has been employed as first-line pharmacological therapy in a subgroup of symptomatic patients with small, radiolucent cholesterol gallstones. Long-term administration of UDCA can promote the dissolution of cholesterol gallstones. However, the optimal use of UDCA is not always achieved in clinical practice because of failure to titrate the dose adequately.
Therefore, the development of novel, effective and noninvasive therapies is crucial for reducing the costs of health care associated with gallstones. In this review, we summarize recent progress in investigating the inhibitory effects of ezetimibe and statins on intestinal absorption and hepatic biosynthesis of cholesterol, respectively, for the treatment of gallstones, as well as in elucidating their molecular mechanisms by which combination therapy could prevent this very common liver disease worldwide.