A 52-year-old postmenopausal woman comes to the office for evaluation of several months of episodic abdominal discomfort and nausea, especially after a fatty meal. She has no past medical history and does not use tobacco, alcohol, or illicit drugs. Her BMI is 33 kg/m2. Physical examination shows a soft, nontender abdomen with normal bowel sounds. Liver span is 8 cm. Murphy sign is negative. Abdominal x-ray reveals no calcifications, but abdominal ultrasound shows a small, non-obstructing gallstone. The patient prefers nonoperative management. Which of the following would best treat this patient's condition?
Show Explanatory Sources
Cholesterol gallstones are the most common type of gallstone. They are primarily composed of cholesterol monohydrate crystals but can contain variable amounts of calcium salts, bilirubin, and mucin. Normally, bile acids and phospholipids solubilize the cholesterol to prevent stone formation. Decreased amounts of bile acids and phospholipids can cause the bile to become supersaturated with cholesterol, allowing it to crystallize and form cholesterol gallstones. Risk factors for stone formation include increasing age, obesity, excessive bile salt loss (eg, terminal ileum disease), and female sex.
Cholecystectomy is the preferred treatment for symptomatic gallstones. However, medical therapy is an option in patients refusing surgery or with high surgical risk. Administration of hydrophilic bile acids (eg, ursodeoxycholic acid) reduces cholesterol secretion and increases biliary bile acid concentration. This improves cholesterol solubility and promotes gallstone dissolution. Although the response to medical therapy is good in patients with mild symptoms and small stones, there is a high rate of gallstone recurrence.
(Choice B) Bile acid sequestrants (eg, cholestyramine) decrease enterohepatic recirculation of bile acids (increase gallstone risk). However, they also stimulate the conversion of cholesterol to bile acids and increase biliary motility (decrease gallstone risk). The net result is no significant change in the risk of gallstones.
(Choice C) Estrogen increases cholesterol secretion and progesterone reduces bile acid secretion, ultimately causing bile to become supersaturated with cholesterol. Progesterone also slows gallbladder emptying, which causes bile stasis and further promotes gallstone formation.
(Choice D) Fibrates increase cholesterol content in bile, which increases the risk of gallstones.
(Choice E) Iron chelation therapy is used to treat iron overload syndromes but has no significant effect on gallstones.
(Choice F) Phosphate-binding agents can lower serum phosphate in chronic kidney disease and dialysis patients but do not significantly affect gallstones.
(Choice G) Very low-calorie diets with decreased caloric intake and rapid weight loss can lead to bile stasis and increased cholesterol mobilization, increasing the risk of gallstone formation.
Educational objective:
Medical therapy to dissolve cholesterol gallstones is an option in patients refusing cholecystectomy or with high surgical risk. Hydrophilic bile acids (eg, ursodeoxycholic acid) improve cholesterol solubility by reducing the amount of cholesterol secreted into the bile and increasing biliary bile acid concentration.