Gallstones and gallbladder disease - Risk Factors

Description

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

Alternative Names

Cholecystitis; Choledocholithiasis; Bile duct stones

Risk Factors:

More than 25 million Americans have gallstones, and a million are diagnosed each year. However, only 1 - 3% of the population complains of symptoms during the course of a year, and fewer than half of these people have symptoms that return.

Risk Factors in Women

Women are much more likely than men to develop gallstones. Gallstones occur in nearly 25% of women in the U.S. by age 60, and as many as 50% by age 75. In most cases, they have no symptoms. 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 if possible. In fact, gallstones may disappear after delivery. If surgery is necessary, laparoscopy is the safest approach.

Hormone Replacement Therapy. Several large studies have shown that the use of hormone replacement therapy (HRT) doubles or triples the risk for gallstones, hospitalization for gallbladder disease, or gallbladder surgery. Estrogen raises triglycerides, a fatty acid that increases the risk for cholesterol stones. How the hormones are delivered may make a difference, however. Women who use a patch or gel form of HRT face less risk than those who take a pill. HRT may also be a less-than-attractive option for women because studies have shown it has negative effects on the heart and increases the risk for breast cancer.

Risk Factors in Men

About 20% of men have gallstones by the time they reach age 75. Because most cases do not have symptoms, 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 gallbladder removed are more likely to have severe disease and surgical complications than women.

Risks in Children

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

• Spinal injury
• History of abdominal surgery
• Sickle-cell anemia
• Impaired immune system
• Receiving nutrition through a vein (intravenous)

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 do people of Asian and African descent. 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. 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. Up to one-third of cases of painful gallstones may be related to genetic factors.

A mutation in the gene ABCG8 significantly increases a person's risk of gallstones. This gene controls a cholesterol pump that transports cholesterol from the liver to the bile duct. It appears this mutation may cause the pump to continuously work at a high rate.

Defects in transport proteins involved in biliary lipid secretion appear to predispose certain people to gallstone disease, but this alone many not be sufficient to create gallstones. Studies indicate that the disease is complex and may result from the interaction between genetics and environment. Some studies suggest immune and inflammatory mediators may play key roles.

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 have worse infections.

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.

Weight Cycling. Rapid weight loss or cycling (dieting and then putting weight back on) further increases cholesterol production in the liver, which results in supersaturation and an increased risk for gallstones.

• The risk for gallstones is as high as 12% after 8 -16 weeks of restricted-calorie diets.
• The risk is more than 30% within 12 - 18 months after gastric bypass surgery.

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

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

Men are also at increased risk for developing gallstones when their weight fluctuates. The risk increases proportionately with dramatic weight changes as well as with frequent weight cycling.

Bariatric Surgery. Patients who have either Roux-en-Y or laparoscopic banding bariatric surgery are at increased risk for gallstones. For this reason, many centers request that patients undergo cholecystectomy before their bariatric procedure. However, doctors are now questioning this practice.

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, High Triglycerides and Their Treatment

Although gallstones are formed from the supersaturation of cholesterol in the bile, high total cholesterol levels themselves are not necessarily associated with gallstones. Gallstone formation is associated with low levels of "good" HDL cholesterol and high triglyceride levels. Some evidence suggests that high levels of triglycerides may impair the 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. These medications include gemfibrozil (Lopid) and fenofibrate (Tricor). Other cholesterol-lowering drugs do not have this effect. [For more information, 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. Up to 40% of patients on home intravenous nutrition develop gallstones, and the risk may be higher in patients on total intravenous nutrition. It is suspected that the cause is lack of stimulation in the gut, because patients who also take some food by mouth have less risk of developing gallstones. However, treatment for gallstones in this population is associated with a low risk of complications.

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 age 60 and those who have had numerous bowel operations (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 of gallstones. The complications can be so severe that some organ transplant centers require the patient's gallbladder be removed before the transplant is performed.

Medications. Octreotide (Sandostatin) poses a risk for gallstones. In addition, 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.

Heme Iron. High consumption of heme iron, the type of iron found in meat and seafood, has been shown to lead to gallstone formation in men. Gallstones are not associated with diets high in non-heme iron foods such as beans, lentils, and enriched grains.

Resources

• http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
• www.gastro.org -- American Gastroenterological Association
• www.acg.gi.org -- American College of Gastroenterology
• www.liverfoundation.org -- American Liver Foundation

References

Afdhal NH. Diseases of the Gallbladder and Bile Ducts. In: Goldman L, Ausiello D. (eds.). Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007.

Chambrlain RS, Sakpal SV. A comprehensive review of single-incision laparoscopic surgery (SILS) and natural orifice transluminal endoscopic surgery (NOTES) techniques for cholecystectomy. J Gastrointest Surg. 2009 May 2 [Epub ahead of print].

Chari RS, Shah SA. Biliary system. In: Townsend CM, Beauchamp RD, Evers BM, Mattox KL. Sabiston Textbook of Surgery. 18th ed. St. Louis, MO: WB Saunders;2007:chap 54.

Dray X, Joy F, Reijasse D, et al. Incidence, risk factors, and complications of cholelithiasis in patients with home parenteral nutrition. J Am Coll Surg. 2007;204(1):13-21.

Gurusamy, KS, Samraj K. Cholecystectomy versus no cholecystectomy in patients with silent gallstones. Cochrane Database Syst Rev. 2007;(1):CD006230.

Ito K, Ito H, Whang EE. Timing of Cholecystectomy for Biliary Pancreatitis: Do the Data Support Current Guidelines? J Gastrointest Surg. 2008 Jul 18 [Epub ahead of print].

Konstantinidis IT, Deshpande V, Genevay M, Berger D, Fernandez-del Castillo C, Tanabe KK, et al. Trends in presentation and survival for gallbladder cancer during a period of more than four decades. Arch Surg. 2009;144(5):441-447.

Liu B, Beral V, Balkwill A, Green J, Sweetland S, Reeves G, et al. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women. BMJ. 2008;337:a386. Doi: 10.1136/bmj.a386.

Portenier DD, Grant JP, Blackwood HS, et al. Expectant management of the asymptomatic gallbladder at Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2007; 3(4):476-479.

Rosing DK, de Virgilio C, Yaghoubian A, et al. Early cholecystectomy for mild to moderate gallstone pancreatitis shortens hospital stay. J Am Coll Surg. 2007;205(6):762-766.

Strasberg SM. Acute calculous cholecystitis. N Engl J Med. 2008;358(26):2804-2811.

Tse F, Liu L, Barkun AN, Armstrong D, Moayyedi P. EUS: a meta-analysis of test performance in suspected choledocholithiasis. Gastrointest Endosc. 2008;67(2):235-244.

Verbesey JE, Birkett DH. Common bile duct exploration for choledocholithiasis. Surg Clin N Am. 2008;88(6):1315-1328.

Williams EJ, Green J, Beckingham I, et al. Guidelines on the management of common bile duct stones (CBDS). Gut. 2008;57(7):1004-1021.

• Reviewed last on: 6/26/2009
• Reviewed by: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

Source: http://www.umm.edu/patiented/articles/who_gets_gallstones_gallbladder_disease_000010_4.htm#ixzz2QnxUrMTi
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