title: Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol.
abstract: 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 physical-chemical balance of cholesterol solubility in bile is disturbed.
  
  
  METHODS
  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.
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
authors: Helen H
authors: HH
authors: Wang
authors: Piero
authors: P
authors: Portincasa
authors: Ornella
authors: O
authors: de Bari
authors: Kristina J
authors: KJ
authors: Liu
authors: Gabriella
authors: G
authors: Garruti
authors: Brent A
authors: BA
authors: Neuschwander-Tetri
authors: David Q-H
authors: DQ
authors: Wang
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002784:Cholesterol / Q000378:metabolism*; D000069438:Ezetimibe; D042882:Gallstones / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D002756:Cholagogues and Choleretics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D000069438:Ezetimibe