Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

Helen H. Wang, Piero Portincasa, Ornella de Bari, Kristina J. Liu, Gabriella Garruti, Brent A. Neuschwander-Tetri, David Q.H. Wang

Research output: Contribution to journalReview article

31 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)413-426
Number of pages14
JournalEuropean Journal of Clinical Investigation
Volume43
Issue number4
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Fingerprint

Biosynthesis
Intestinal Absorption
Gallstones
Cholesterol
Liver
Ursodeoxycholic Acid
Therapeutics
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cholelithiasis
Laparoscopic Cholecystectomy
Feeding Behavior
Bile Acids and Salts
Health care
Bile
Health Care Costs
Solubility
Surgery
Liver Diseases
Dissolution
Homeostasis

Keywords

  • Bile
  • Bile acid
  • Bile flow
  • Cholesterol crystallization
  • Cholesterol monohydrate crystal
  • Mucin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol. / Wang, Helen H.; Portincasa, Piero; de Bari, Ornella; Liu, Kristina J.; Garruti, Gabriella; Neuschwander-Tetri, Brent A.; Wang, David Q.H.

In: European Journal of Clinical Investigation, Vol. 43, No. 4, 01.04.2013, p. 413-426.

Research output: Contribution to journalReview article

Wang, Helen H. ; Portincasa, Piero ; de Bari, Ornella ; Liu, Kristina J. ; Garruti, Gabriella ; Neuschwander-Tetri, Brent A. ; Wang, David Q.H. / Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol. In: European Journal of Clinical Investigation. 2013 ; Vol. 43, No. 4. pp. 413-426.
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AU - Neuschwander-Tetri, Brent A.

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