16-20: Cholelithiasis (Gallstones)

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

Gallstones are more common in women than in men and increase in incidence in both sexes and all races with age. In the United States, the prevalence of gallstones is 8.6% in women and 5.5% in men. The highest rates are in persons over age 60, and rates are higher in Mexican American persons than in White and Black persons who are not of Latinx descent. Although cholesterol gallstones are less common in Black persons, cholelithiasis attributable to hemolysis occurs in over a third of individuals with sickle cell disease. Persons who are native to either the northern or southern hemisphere have a high rate of cholesterol cholelithiasis, probably because of a predisposition resulting from "thrifty" (LITH) genes that promote efficient calorie utilization and fat storage. As many as 75% of Pima and other American Indian women over 25 years of age have cholelithiasis. Other genetic mutations that predispose persons to gallstones have been identified. Obesity is a risk factor for gallstones, especially in women. Rapid weight loss, as occurs after bariatric surgery, also increases the risk of symptomatic gallstone formation. Diabetes mellitus, glucose intolerance, and insulin resistance are risk factors for gallstones, and a high intake of carbohydrate and high dietary glycemic load increase the risk of cholecystectomy in women. Hypertriglyceridemia may promote gallstone formation by impairing gallbladder motility. The prevalence of gallbladder disease is increased in men (but not women) with cirrhosis and HCV infection. Moreover, cholecystectomy has been reported to be associated with an increased risk of NAFLD and cirrhosis, possibly because gallstones and liver disease share risk factors. Gallstone disease is associated with increased overall, cardiovascular, and cancer mortality.

The incidence of gallstones is high in individuals with Crohn disease; approximately one-third of those with inflammatory involvement of the terminal ileum have gallstones due to disruption of bile salt resorption that results in decreased solubility of the bile. Drugs such as clofibrate, octreotide, and ceftriaxone can cause gallstones. Prolonged fasting (over 5–10 days) can lead to formation of biliary “sludge” (microlithiasis), which usually resolves with refeeding but can lead to gallstones or biliary symptoms. Pregnancy, particularly in obese women and those with insulin resistance, is associated with an increased risk of gallstones and of symptomatic gallbladder disease. Hormone replacement therapy appears to increase the risk of gallbladder disease and need for cholecystectomy; the risk is lower with transdermal than oral therapy. Gallstones detected by population screening have been reported to be associated with an increased risk of right-sided colon cancers. A low-carbohydrate diet and a Mediterranean diet as well as physical activity and cardiorespiratory fitness may help prevent gallstones. Consumption of caffeinated coffee appears to ...