Statins as potential treatment for cholesterol gallstones: an attempt to understand the underlying mechanism of actions

Abstract

Obesity, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), insulin resistance and high-fat diets (unsaturated fats) rich in cholesterol are all associated risk factors for cholesterol gallstones. In view of the high prevalence of cholesterol gallstones, there is an urgent need to understand whether pharmacological therapies can be harnessed for the treatment of cholesterol gallstones. Gallstones are shown to be associated with an increased risk, not only of mortality, but also of CVD. Statins, widely used in prevention of CVD and hypercholesteremia, have been shown to dissolve cholesterol gallstones in animal models and human studies, highlighting the potential for a pharmacological therapy for gallstones. More studies are required to understand the role of statins in the treatment of gallstones and for comparison with current treatment strategies.

Limits and perspective of oral therapy with statins and aspirin for the prevention of symptomatic cholesterol gallstone disease

“…Recent articles have proposed the therapeutic use of statins for the medical treatment of cholesterol gallstones [14]. The reported data about gallstones recurrence after oral biliary salts dissolution is 10% per year [1].…”

“…The combination of statins and ursodeoxycholic acid has been more effective in cholesterol gallstone dissolution than ursodeoxycholic acid treatment alone [14]. Ezetimibe reduces cholesterol concentrations and can inhibit gall bladder stasis secondary to cholesterol-supersaturated bile [15].…”

Ultrastructural basis of the failure of oral dissolution therapy with bile salts and/or statin for cholesterol gallstones

“…In a recent issue of Expert Opinion on Phamacotherapy, an interesting article on the use of statins in the oral treatment of cholesterol gallstones was published [1]. The authors speculated that the therapeutic use of statins in the treatment of cholesterol gallstones could decrease the annual number of cholecystectomies.…”

The association between renal stone disease and cholesterol gallstones: the easy to believe and not hard to retrieve theory of the metabolic syndrome

“…The formation of cholesterol gallstones is thought to be associated with an increased hepatic secretion of cholesterol into bile due to the presence of these metabolic disorders. 8 The only established dietary risk for cholesterol gallstone is a high caloric intake and the distribution of gallstones in different populations appear to be related to high dietary intake of cholesterol and fats (Western diets). Other modifiable risk factors for gallstone and renal stone disease are obesity, metabolic syndrome and rapid weight loss.…”

“…Importantly the incidence of both gallstones and renal stone disease increases with age. 8 The development of diabetes, hypertension and gout are associated with a marked risk of developing chronic kidney disease (CKD) in individuals with chronic renal disease. 9 Due to epidemic of diabetes and obesity, it is expected that the prevalence of cholesterol gallstone and renal stone disease will increase and this will add more to burden of health care authorities.…”