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  • Major risk factors for cholesterol gallstones include age >50 years, female sex, Mexican or Native American ethnicity, genetic predisposition, family history, pregnancy and parity, estrogens, obesity, and the metabolic syndrome.
  • Gallstones are often found incidentally during abdominal ultrasonography, which has >95% sensitivity for cholesterol stones ≥1.5 mm.
  • In ∼80% of cases gallstones remain asymptomatic; in symptomatic patients, biliary colic is almost always present, often radiating to the right scapula or shoulder.
  • Laparoscopic cholecystectomy is indicated in patients with symptomatic gallstones.
  • Major complications of gallstone disease requiring treatment are acute cholecystitis, choledocholithiasis, obstructive jaundice, cholangitis, and pancreatitis.
  • Acute cholangitis caused by an obstructing gallstone should be treated by endoscopic removal of the stone under antibiotic coverage as soon as possible.

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Gallstone disease represents a considerable health problem in Western industrialized countries. With a prevalence of 10–15% in adults in the United States and in Europe, it is one of the most common digestive diseases. In the United States, it is the gastrointestinal disorder that, after gastroesophageal reflux disease, accounts for the second-highest costs. The clinical manifestations of gallstones include episodic abdominal pain, acute cholecystitis, obstructive jaundice, cholangitis, and pancreatitis.

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In Western industrialized countries, >90% of gallstones consist mainly of cholesterol. Thus, in the majority of patients, cholelithiasis may be regarded as a disturbance of cholesterol disposal. A complex solubilizing system in bile is required to keep cholesterol in solution. If this system fails, or if its capacity is exceeded by hypersecretion of cholesterol into bile, cholesterol precipitates and gallstones may develop.

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Epidemiology and Genetics

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In the third National Health and Nutrition Examination Survey (NHANES III), a large epidemiologic survey that compiled data including gallbladder ultrasonography findings, the overall prevalence of gallstones in the United States was 7.9% in men and 16.6% in women, with a progressive increase after age 20 years. The prevalence was high in Mexican Americans (8.9% in men, 26.7% in women), intermediate for non-Hispanic whites (8.6% in men, 16.6% in women), and low for African Americans (5.3% in men, 13.9% in women). Overall prevalence rates in Europe, from large ultrasonic surveys in adults aged 30–69 years, are similar to those in the NHANES III study. The prevalence of gallstone disease is lower in Asians (ranging from 3% to 15%) and very low (<5%) in Africans. Certain ethnic groups are particularly susceptible; among Native Americans in the western United States, the prevalence of gallstones is over 75%.

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Epidemiologic surveys and family clustering point to the critical role of genetics in determining susceptibility to gallstones. The genetic component in the pathogenesis of symptomatic gallstone disease in the Swedish population has been estimated to be about 25%. A single nucleotide polymorphism conferring an increased risk of gallstone formation has been identified in the hepatic cholesterol transporter ABCG5/G8 of patients with gallstones. In a recent genome-wide analysis of serum bilirubin levels, the uridine diphosphate-glucuronyltransferease 1A1 (UGT1A1) Gilbert syndrome gene variant was associated with gallstone disease and with the presence of bilirubin in gallstones in men. Since most gallstones associated with the UGT1A1 variant were ...

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