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Recent understanding of cholesterol gallstone pathogenesis: implication to non-surgical therapeutic strategy

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Abstract

This article reviews the recent understanding of cholesterol gallstone pathogenesis in light of etiology and molecular mechanisms of the cholesterol gallstone formation process, to provide the future direction of a non-surgical therapeutic strategy. In principle, cholesterol gallstone formation, which is associated with an altered bile salt metabolism, is based primarily upon the impairment of cholesterol metabolism and homeostasis. Cholesterol is eliminated physiologically into bile; thus, the excess cholesterol induces bile metastability due to a relative insufficiency of bile salt, to initiate cholesterol crystal nucleation in the gallbladder with an impaired function. Those crystals grow to become macroscopic stones in the gallbladder mucin gel, accumulated under an arachidonate-prostanoid pathway induced-hypersecretion by the gallbladder wall. These events can be modified by bile salt supplementation, which provides a detergent action. Therefore, oral bile salt administration is a cost-effective, non-surgical therapy under certain circumstances. Understanding the pathogenesis of cholesterol gallstones attributes to the therapeutic guideline based upon scientific and clinical evidence.

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Abbreviations

ABC:

ATP binding cassette family of transporters

FXR:

Farnesoid X receptor

LXR:

Liver X receptor

PFIC:

Progressive familial intrahepatic cholestasis

PXR:

Pregnane X receptor

RXR:

Retinoid X receptor

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Acknowledgments

This work was supported in part by the Health and Labour Sciences Research Grant for Intrahepatic Gallstones awarded to S. Tazuma.

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Authors and Affiliations

  1. Department of General Medicine, Hiroshima University Hospital, Hiroshima, Japan

    Susumu Tazuma

  2. Department of Clinical Pharmacotherapy, Programs of Applied Medicine, Graduate School of Medical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Susumu Tazuma

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Correspondence to Susumu Tazuma.

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Tazuma, S. Recent understanding of cholesterol gallstone pathogenesis: implication to non-surgical therapeutic strategy. Clin J Gastroenterol 1, 87–92 (2008). https://doi.org/10.1007/s12328-008-0031-2

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