Journal
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Volume 43, Issue 4, Pages 413-426Publisher
WILEY
DOI: 10.1111/eci.12058
Keywords
Bile; bile acid; bile flow; cholesterol crystallization; cholesterol monohydrate crystal; mucin
Funding
- National Institutes of Health (US Public Health Service) [DK73917]
- Saint Louis University Liver Center Seed Grant Award
- Saint Louis University President's Research Fund
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [FIRB2003, RBAU01RANB002]
- Fondazione Cassa di Risparmio di Puglia (Ricerca Scientifica e Tecnologica)
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Background 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 physicalchemical balance of cholesterol solubility in bile is disturbed. Design 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. Results 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. Conclusions 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.
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