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Gallstones and gallbladder disease

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of gallstones.

Alternative Names

Cholecystitis; Choledocholithiasis; Bile duct stones

Risk Factors

About 20 million Americans harbor gallstones. Only 1 - 3% of the population, however, complains of symptoms during the course of a year, and less than half of these people will experience recurrent symptoms.

Risk Factors in Women

Women are much more likely than men to develop gallstones. They occur in nearly 25% of women in the US by age 60 and up to 50% by age 75. (Again, in most cases they are asymptomatic.) In general, women are probably at increased risk because estrogen stimulates the liver to remove more cholesterol from blood and divert it into the bile.

Pregnancy. Pregnancy increases the risk for gallstones, and pregnant women with stones are more likely to have symptoms than nonpregnant women. Surgery should be delayed until after delivery in most cases. In fact, gallstones may disappear after delivery. If surgery is needed laparoscopy is the safer approach.

Hormone Replacement Therapy. Several large studies have shown that use of hormone replacement therapy (HRT) doubles or triples the risk for gallstones or gallbladder surgery. A 2005 Journal of the American Medical Association study found that while all types of HRT raise the risks, estrogen alone has higher risks than combined estrogen and progesterone therapy. Estrogen has an effect on the liver and raises triglycerides, a fatty acid that increases the risk for cholesterol stones. Recent studies on HRT reporting negative effects on the heart and increased risks for breast cancer are also making this treatment a less attractive option for most postmenopausal women.

Risk Factors in Men

About 20% of men have gallstones by the time they reach 75 years of age. Because most cases are asymptomatic, however, the rates may be underestimated in elderly men. One study of nursing home residents reported that 66% of the women and 51% of the men had gallstones. Men who have their gallbladders removed, moreover, are more likely to have severe disease and operative complications than women.

Risks in Children

Gallstone disease is relatively rare in children. When gallstones occur in this age group they are more likely to be pigment stones. Girls do not seem to be more at risk than boys are. The following conditions may put children at higher risk:

• Spinal injury.
• History of abdominal surgery.
• Sickle-cell anemia.
• Impaired immune system.
• Intravenous nutrition.

Ethnicity

Because gallstones are related to diet, particularly fat intake, the incidence of gallstones varies widely among nations and regions. For example, Hispanics and Northern Europeans have a higher risk for gallstones than people of Asian and African descent do. (People of Asian descent who develop gallstones are most likely to have the brown pigment type.)

Native North and South Americans, such as Pima Indians in the U.S. and native populations in Chile and Peru, are especially prone to developing gallstones. Pima women have an 80% chance of developing gallstones during their lives and virtually all Native Indian females in Chile and Peru develop gallstones during their lifetimes. Such cases are most likely due to a combination of genetic and dietary factors.

Genetics

Having a family member or close relative with gallstones may increase the risk of gallstones. Up to a third of cases of painful gallstones may be related to genetic factors, although the genetics of gallbladder disease remains poorly understood. Many genes may be involved, including those that lead to obesity or other risk factors that predispose to gallstones.

Diabetes

People with diabetes are at higher risk for gallstones and have a higher than average risk for acalculous gallbladder disease (without stones). Gallbladder disease may progress more rapidly in patients with diabetes, who tend to suffer worse infections in general.

Obesity and Weight Changes

Obesity. Being overweight is a significant risk factor for gallstones. In such cases, the liver over-produces cholesterol, which is delivered into the bile and causes it to become supersaturated. Some evidence suggests that specific dietary factors (saturated fats and refined sugars) are the primary culprit in these cases, although studies are conflicting. Animal studies, however, suggest that obesity itself, not any particular foods, triggers the process leading to cholesterol supersaturation and the formation of stones.

Weight Cycling. Rapid weight loss or cycling (dieting and then putting back weight) further increases cholesterol production in the liver, with resulting supersaturation and risk for gallstones. A 2000 study suggested the following rates for gallstones related to extreme and rapid weight loss:

• The risk for gallstones is as high as 12% after eight to 16 weeks of restricted calorie diets.
• The risk is more than 30% within a year to 18 months after gastric by-pass surgery.

About one-third of gallstone cases in these situations are symptomatic. The risk for gallstones is highest in the following dieters:

• Those who lose more than 24% of their initial body weight.
• Those who lose more than 1.5 kg (3.3. lb.) a week.
• Those on very low-fat, low-calorie diets.

Weight cycling also puts people at risk for gallstones. For example, a 16-year study found that the risk for gallstone surgery was 68% higher for women who lost and then regained more than 20 pounds at least once than in women whose weight remained stable.

Metabolic Syndrome

Metabolic syndrome is a cluster of conditions that includes obesity (especially belly fat), low HDL (good) cholesterol, high triglycerides, high blood pressure, and high blood sugar. Research suggests that metabolic syndrome is a risk factor for gallstones.

Low HDL Cholesterol and High Triglycerides and Their Treatment

Although gallstones are formed from supersaturation of cholesterol in the bile, high total cholesterol levels themselves are not necessarily associated with gallstones. Gallstone formation, however, is associated with low HDL cholesterol (the so-called good cholesterol) levels and high triglyceride levels. Some evidence suggests that high triglyceride levels may impair emptying actions of the gallbladder.

Unfortunately some fibrates, drugs used to correct these conditions, actually increase the risk for gallstones by increasing the amount of cholesterol secreted into the bile. They include gemfibrozil (Lopid), fenofibrate (Tricor), and bezafibrate (Bezalip). (Other cholesterol-lowering agents do not have this effect at all.) [See In-Depth Report #23: Cholesterol.]

Other Risk Factors

Prolonged Intravenous Feeding. Prolonged intravenous feeding reduces the flow of bile and increases the risk for gallstones.

Crohn's Disease . Crohn's disease, an inflammatory bowel disorder, leads to poor reabsorption of bile salts from the digestive tract and substantially increases the risk of gallbladder disease. Patients over 60 and those who have had numerous bowel surgeries (particularly in the region where the small and large bowel meet) are at especially high risk.

Cirrhosis. Cirrhosis poses a major risk for gallstones, particularly pigment gallstones.

Organ Transplantation. Bone marrow or solid organ transplantation increases the risk.

Medications. Octreotide (Sandostatin) poses a risk for gallstones. In addition the cholesterol-lowering drugs known as fibrates and thiazide diuretics may slightly increase the risk for gallstones.

Blood Disorders. Chronic hemolytic anemia, including sickle cell anemia, increases the risk for pigment gallstones.

• Review Date: 6/12/2006
• Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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