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

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.
European Journal of Clinical Investigation (Impact Factor: 2.73). 02/2013; 43(4). DOI: 10.1111/eci.12058
Source: PubMed


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.

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.

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.

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.

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Available from: Gabriella Garruti, Oct 13, 2014
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    • "The relationship between statins and symptomatic gallstone disease is still more or less conflicting, although several studies have reported a significant reduction in the incidence of symptomatic gallstones disease in patients using statin therapy [9]. The most consistent evidence is that bile is desaturated of cholesterol after the long-term administration of statins [10,11]. These observations suggest that statins may reduce the size of cholesterol particles and, subsequently, prohibit gallstone formation and reduce the size of gallstones; therefore, they may also affect the course of symptomatic gallstone disease. "
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    ABSTRACT: Background Statins can modify bile cholesterol and, thus, the formation of gallstones. We examined whether statin use also modifies the severity of symptomatic gallstone disease and its treatment. Methods A total of 1,140 consecutive patients with symptomatic gallstone disease were recruited during 2008-2010 at Kuopio university hospital, Finland. Case-control analysis matched the patients using (n = 272) or not using (n = 272) statins by age and sex. The baseline characteristics of the patients, need and type of surgical treatment, duration of operation, perioperative bleeding, postoperative complications and overall mortality rate were compared statistically between the study groups. Results Morbidity and subsequent polypharmacy occurred more frequently among the patients with statins compared to the patients without statins. There were no significant differences between the statin users and non-users regarding surgical treatment (open vs. laparoscopic cholecystectomy). The mean operation time for laparoscopic cholecystectomy was 10% shorter for the patients with statin use than for the patients without. In addition, there was a non-significant tendency for statin users to bleed less during laparoscopic operations than the non-users. There were no differences in other procedure-related parameters (e.g., operation urgency, conversions, choledochotomies, complications and mortality) in patients with or without statins. Conclusions Compared to no treatment, statin treatment was associated with a shorter operation time for laparoscopy cholecystectomy. Other surgical outcome parameters were similar in patients with or without statins, although statin users had more polypharmacy and circulatory illnesses than non-users.
    BMC Gastroenterology 07/2014; 14(1):119. DOI:10.1186/1471-230X-14-119 · 2.37 Impact Factor
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    ABSTRACT: Gallstone disease represents an important issue in the healthcare system. The principal non-invasive non-surgical medical treatment for cholesterol gallstones is still represented by oral litholysis with bile acids. The first successful and documented dissolution of cholesterol gallstones was achieved in 1972. Since then a large number of investigators all over the world, have been dedicated in biochemical and clinical studies on ursodeoxycholic acid (UDCA), demonstrating its extreme versatility. This editorial is aimed to provide a brief review of recent developments in UDCA use, current indications for its use and, the more recent advances in understanding its effects in terms of an anti-inflammatory drug.
    World Journal of Gastroenterology 08/2013; 19(31):5029-34. DOI:10.3748/wjg.v19.i31.5029 · 2.37 Impact Factor
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    ABSTRACT: Cholesterol gallstones are a digestive disease of high prevalence that has many risk factors; for this reason, research has focused mainly on how to prevent it rather than how to treat it. Many molecules of the hepatic, bile and intestinal systems are involved in the pathophysiology of this disease, making it very difficult to find a therapeutic target. The pharmacological treatment is limited, so when gallstones generate symptoms, medical treatment indicates gallbladder removal. Ursodeoxycholic acid is used to dissolve cholesterol stones, and ezetimibe and statins are other drugs with possible applications in the treatment of this disease. Given the small number of drugs that have been developed for treating this disease, the research of natural products becomes of paramount importance. Resources such as black radish, glucosinolates, fenugreek, capsaicin, curcumin, garlic, and onion, have all shown significant effects in the prevention and treatment of cholesterol gallstones. In this review, we made a synthesis of the scientific reports that deal with these natural products and that can serve as antecedents for finding a way to treat the most common disease of the gallbladder.
    08/2013; 3(3). DOI:10.5667/tang.2013.0014
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