Medicinal treatments of cholesterol gallstones

Old, current and new perspectives

P. Portincasa, Agostino Di Ciaula, Helen H. Wang, Antonio Moschetta, David Q.H. Wang

Research output: Contribution to journalReview article

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1531-1542
Number of pages12
JournalCurrent Medicinal Chemistry
Volume16
Issue number12
DOIs
StatePublished - May 25 2009
Externally publishedYes

Fingerprint

Gallstones
Cholesterol
Therapeutics
Gallbladder
Bile Acids and Salts
Cystic Duct
Ursodeoxycholic Acid
Cost of Illness
Cholelithiasis
Laparoscopic Cholecystectomy
Intestinal Absorption
Cytoplasmic and Nuclear Receptors
Bile
Ducts
Patient Selection
Dissolution
Animals
Homeostasis
Animal Models
Costs

Keywords

  • Bile
  • Bile salts
  • Dissolution therapy
  • Ezetimibe
  • Gallbladder
  • Intestine
  • Nuclear receptors

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Medicinal treatments of cholesterol gallstones : Old, current and new perspectives. / Portincasa, P.; Di Ciaula, Agostino; Wang, Helen H.; Moschetta, Antonio; Wang, David Q.H.

In: Current Medicinal Chemistry, Vol. 16, No. 12, 25.05.2009, p. 1531-1542.

Research output: Contribution to journalReview article

Portincasa, P. ; Di Ciaula, Agostino ; Wang, Helen H. ; Moschetta, Antonio ; Wang, David Q.H. / Medicinal treatments of cholesterol gallstones : Old, current and new perspectives. In: Current Medicinal Chemistry. 2009 ; Vol. 16, No. 12. pp. 1531-1542.
@article{999f4eb427e1431f92a67b6d24f391c1,
title = "Medicinal treatments of cholesterol gallstones: Old, current and new perspectives",
abstract = "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 = "Bile, Bile salts, Dissolution therapy, Ezetimibe, Gallbladder, Intestine, Nuclear receptors",
author = "P. Portincasa and {Di Ciaula}, Agostino and Wang, {Helen H.} and Antonio Moschetta and Wang, {David Q.H.}",
year = "2009",
month = "5",
day = "25",
doi = "10.2174/092986709787909631",
language = "English (US)",
volume = "16",
pages = "1531--1542",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "12",

}

TY - JOUR

T1 - Medicinal treatments of cholesterol gallstones

T2 - Old, current and new perspectives

AU - Portincasa, P.

AU - Di Ciaula, Agostino

AU - Wang, Helen H.

AU - Moschetta, Antonio

AU - Wang, David Q.H.

PY - 2009/5/25

Y1 - 2009/5/25

N2 - 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.

AB - 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.

KW - Bile

KW - Bile salts

KW - Dissolution therapy

KW - Ezetimibe

KW - Gallbladder

KW - Intestine

KW - Nuclear receptors

UR - http://www.scopus.com/inward/record.url?scp=65649131929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65649131929&partnerID=8YFLogxK

U2 - 10.2174/092986709787909631

DO - 10.2174/092986709787909631

M3 - Review article

VL - 16

SP - 1531

EP - 1542

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 12

ER -