Targets for Current Pharmacologic Therapy in Cholesterol Gallstone Disease

https://doi.org/10.1016/j.gtc.2010.02.005Get rights and content

Section snippets

Guidelines for management of gallstone disease

Gallbladder stones are frequently found in asymptomatic patients during routine abdominal ultrasonography, because in most cases (60%–80%) gallstones do not generate symptoms.43, 48, 49 Previous observations have shown that the average risk of developing symptomatic gallstones is 2.0% to 2.6% per year.45, 50 By contrast, the presence of microstones and sludge in the gallbladder is a major risk factor for the development of biliary pain and complicated gallstone disease, and also plays a main

Treatment of the Biliary Colic

The presence of a gallstone of any type and size may put the patient at risk of biliary pain. As the intensity of pain is usually high (mean visual analog scale of 9 cm on a 0- to 10-cm scale), patients require immediate medical attention and analgesia. The pain is not exclusively postprandial, and is typically intermittent. The most frequent localization is the right upper quadrant of the abdomen and/or the epigastrium (representative dermatomes T8/9), and the duration is generally longer than

Novel medical treatments

The presence of a lithogenic bile is primarily a result of a sustained hypersecretion of biliary cholesterol, which has 2 key components: hepatic and intestinal.31 In principle, drugs influencing hepatic synthesis and/or secretion of cholesterol (ie, statins) and/or intestinal absorption of cholesterol (ie, EZT) are potentially able to influence the formation of cholesterol gallstones and to promote dissolution of gallstones.

Summary

The advent of laparoscopic cholecystectomy has moved the interest away from the pharmacologic treatment of gallstones. Medical therapy is restricted to a scant group of symptomatic (colicky pain) well-selected patients, in which the unfavorable cost-benefit analyses and a high rate of gallstone recurrence play a negative role. Following early cholelitholytic therapies with the oral bile acid UDCA, recent studies indicate that the research agenda should include studies on the role of gallstone (

Acknowledgments

The authors are grateful to Paola De Benedictis, Rosa De Venuto, and Michele Persichella for their skillful technical assistance.

First page preview

First page preview
Click to open first page preview
View PDF

References (175)

  • F. Nakayama et al.

    Changing state of gallstone disease in Japan. Composition of the stones and treatment of the condition

    Am J Surg

    (1970)
  • M. Nagase et al.

    Present features of gallstones in Japan. A collective review of 2,144 cases

    Am J Surg

    (1978)
  • D.Q.H. Wang et al.

    High cholesterol absorption efficiency and rapid biliary secretion of chylomicron remnant cholesterol enhance cholelithogenesis in gallstone-susceptible mice

    Biochim Biophys Acta

    (2005)
  • F. Lammert et al.

    Gallstone disease: from genes to evidence-based therapy

    J Hepatol

    (2008)
  • P. Kovacs et al.

    Variation of the gene encoding the nuclear bile salt receptor FXR and gallstone susceptibility in mice and humans

    J Hepatol

    (2008)
  • S.W. Van Mil et al.

    Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy

    Gastroenterology

    (2007)
  • P. Portincasa et al.

    Gallstone disease: symptoms and diagnosis of gallbladder stones

    Best Pract Res Clin Gastroenterol

    (2006)
  • A.K. Diehl et al.

    Clinical evaluation for gallstone disease: usefulness of symptoms and signs in diagnosis

    Am J Med

    (1990)
  • G.D. Friedman et al.

    Prognosis of gallstones with mild or no symptoms: 25 years of follow-up in a health maintenance organization

    J Clin Epidemiol

    (1989)
  • R. Hou et al.

    Lowering low-density lipoprotein cholesterol: statins, ezetimibe, bile acid sequestrants, and combinations: comparative efficacy and safety

    Endocrinol Metab Clin North Am

    (2009)
  • H.H. Wang et al.

    Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones

    Gastroenterology

    (2008)
  • G.H. Elta et al.

    Meperidine need not be proscribed during sphincter of Oddi manometry

    Gastrointest Endosc

    (1994)
  • E.A. Akriviadis et al.

    Treatment of biliary colic with diclofenac: a randomized, double-blind, placebo-controlled study

    Gastroenterology

    (1997)
  • G.D. Friedman

    Natural history of asymptomatic and symptomatic gallstones

    Am J Surg

    (1993)
  • A. Lanzini et al.

    Maintenance of hepatic bile acid secretion rate during overnight fasting by bedtime bile acid administration

    Gastroenterology

    (1988)
  • P. Portincasa et al.

    Behavior of various cholesterol crystals in bile from gallstone patients

    Hepatology

    (1996)
  • A. Moschetta et al.

    Cholesterol crystallization in model biles. Effects of bile salt and phospholipid species composition

    J Lipid Res

    (2001)
  • W.G. Hardison et al.

    Effect of ursodeoxycholate and its taurine conjugate on bile acid synthesis and cholesterol absorption

    Gastroenterology

    (1984)
  • Z.L. Xiao et al.

    Hydrophilic but not hydrophobic bile acids prevent gallbladder muscle dysfunction in acute cholecystitis

    Hepatology

    (2003)
  • K.J. Maurer et al.

    T-cell function is critical for murine cholesterol gallstone formation

    Gastroenterology

    (2007)
  • J.G. Pauletzki et al.

    Gallbladder emptying and gallstone formation: a prospective study on gallstone recurrence

    Gastroenterology

    (1996)
  • P. Portincasa et al.

    Apolipoprotein (Apo) E4 genotype and galbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy

    Hepatology

    (1996)
  • N.G. Venneman et al.

    Absence of apolipoprotein E4 genotype, good gallbladder motility and presence of solitary stones delay rather than prevent gallstone recurrence after extracorporeal shock wave lithotripsy

    J Hepatol

    (2001)
  • D. Festi et al.

    Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution

    Gastroenterology

    (1990)
  • M. Sackmann et al.

    Gallbladder emptying is an important factor in fragment disappearance after shock wave lithotripsy

    J Hepatol

    (1993)
  • D.Q. Wang et al.

    Genetic analysis of cholesterol gallstone formation: searching for Lith (gallstone) genes

    Curr Gastroenterol Rep

    (2004)

  • Action plan for liver disease research

    (2004)
  • A.F. Attili et al.

    Epidemiology of gallstone disease in Italy: prevalence data of the multicenter italian study on cholelithiasis (M.I.C.O.L

    Am J Epidemiol

    (1995)
  • S. Sherlock et al.

    Diseases of the liver and biliary system

    (2002)
  • S.M. Grundy et al.

    Metabolic and health complications of obesity

    Dis Mon

    (1990)
  • S.M. Grundy

    Metabolic syndrome scientific statement by the American Heart Association and the National Heart, Lung, and Blood Institute

    Arterioscler Thromb Vasc Biol

    (2005)
  • S.M. Grundy et al.

    Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

    Circulation

    (2005)
  • E.S. Ford et al.

    Increasing prevalence of the metabolic syndrome among US adults

    Diabetes Care

    (2004)
  • E.S. Ford

    Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the US

    Diabetes Care

    (2005)
  • C.J. Tsai et al.

    Dietary protein and the risk of cholecystectomy in a cohort of US women: the Nurses' Health Study

    Am J Epidemiol

    (2004)
  • C.J. Tsai et al.

    Long-term intake of dietary fiber and decreased risk of cholecystectomy in women

    Am J Gastroenterol

    (2004)
  • C.J. Tsai et al.

    Long-term intake of trans-fatty acids and risk of gallstone disease in men

    Arch Intern Med

    (2005)
  • M.F. Leitzmann et al.

    Recreational physical activity and the risk of cholecystectomy in women

    N Engl J Med

    (1999)
  • C.J. Tsai et al.

    The effect of long-term intake of cis unsaturated fats on the risk for gallstone disease in men: a prospective cohort study

    Ann Intern Med

    (2004)
  • M.F. Leitzmann et al.

    The relation of physical activity to risk for symptomatic gallstone disease in men

    Ann Intern Med

    (1998)

    • Cited by (0)

    This work was supported in part by research grants from the Italian Ministry of University and Research (FIRB 2003 RBAU01RANB002), the Italian National Research Council (CNR) (short-term mobility grant 2005), the University of Bari (grants ORBA09XZZT, ORBA08YHKX) (PP), and from the National Institutes of Health (US Public Health Service) (research grants DK54012 and DK73917) (DQ-HW).

    View full text
    Copyright © 2010 Elsevier Inc. All rights reserved.