SeHCAT
Encyclopedia
SeHCAT is the usual name for 23-seleno-25-homo-tauro-cholic acid (selenium homocholic acid taurine or tauroselcholic acid). It is used in a clinical test to diagnose bile acid malabsorption
Bile acid malabsorption
Bile acid malabsorption is a cause of chronic diarrhea. It can result from malabsorption secondary to gastro-intestinal disease or be a primary disorder. Treatment with bile acid sequestrants is often effective.-Classification:...

.

Development

SeHCAT is a taurine-conjugated bile acid
Bile acid
Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...

 analog which was synthesized for use as a radiopharmaceutical to investigate in vivo the enterohepatic circulation
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....

 of bile salts. By incorporating the gamma-emitter 75Se into the SeHCAT molecule, the retention in the body or the loss of this compound into the feces could be studied easily using a standard gamma camera, available in most clinical nuclear medicine
Nuclear medicine
In nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...

 departments.

SeHCAT has been shown to be absorbed from the gut and excreted into the bile at the same rate as cholic acid
Cholic acid
Cholic acid is a bile acid, a white crystalline substance insoluble in water , with a melting point of 200-201 °C. Salts of cholic acid are called cholates. Cholic acid, along with chenodeoxycholic acid, is one of two major bile acids produced by the liver where it is synthesized from cholesterol...

, one of the major natural bile acids in humans. It undergoes secretion into the biliary tree, gallbladder and intestine in response to food, and is reabsorbed efficiently in the ileum, with kinetics similar to natural bile acids. It was soon shown to be the most convenient and accurate method available to assess and measure bile acid
Bile acid
Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...

 turnover in the intestine. SeHCAT testing was commercially developed by Amersham International Ltd (Amersham plc
Amersham plc
Amersham plc was a UK pharmaceutical company, specializing in medical diagnostics and life science products. It was listed on the London Stock Exchange and was once a constituent of the FTSE 100 Index but was purchased by General Electric; it is now part of GE Healthcare.-History:The company had...

 is now part of GE Healthcare
GE Healthcare
GE Healthcare is a division of GE Technology Infrastructure, which is itself a division of General Electric . It employs more than 46,000 people worldwide and is headquartered in Little Chalfont, Buckinghamshire, United Kingdom. GE Healthcare is the first GE business segment to be headquartered...

 Medical Diagnostics division) for clinical use to investigate malabsorption
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...

 in patients with diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

. This test has replaced 14C-labeled glycocholic acid (or taurocholic acid) breath tests and fecal bile acid measurements, which now have no place in the routine clinical investigation of malabsorption
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...

.

SeHCAT test procedure

A capsule containing radiolabelled 75SeHCAT (with 370kBq of Selenium-75 and less than 0.1 mg SeHCAT) is taken orally. The physical half life of 75Se is approximately 118 days; activity is adjusted to a standard reference date. Patients are often fasted before taking the capsule and swallow water to ensure passage of the capsule into the gastrointestinal tract. The effective dose of radiation for an adult given 370kBq of SeHCAT is 0.26mSv. (For comparison, the radiation exposure from an abdominal CT scan is quoted at 5.3mSv and annual background exposure in the UK 1-3mSv.) Measurements were originally performed with a whole body counter but are usually performed now with an uncollimated gamma camera. The patient is scanned supine or prone with anterior and posterior acquisition from head to thigh 1 to 3 hours after taking the capsule. Scanning is repeated after 7 days. Background values are subtracted and care must be taken to avoid external sources of radiation in a nuclear medicine department.

From these measurements, the percent retention of SeHCAT at 7 days is calculated. A 7-day SeHCAT retention value greater than 15% is considered to be normal, with values less than 15% signifing excessive bile acid loss, as found in bile acid malabsorption
Bile acid malabsorption
Bile acid malabsorption is a cause of chronic diarrhea. It can result from malabsorption secondary to gastro-intestinal disease or be a primary disorder. Treatment with bile acid sequestrants is often effective.-Classification:...

.

With more frequent measurements, it is possible to calculate SeHCAT retention whole body half-life; this is not routinely measured in a clinical setting. A half-life of greater than 2.8 days has been quoted as normal.

Clinical Use of the SeHCAT test

The SeHCAT test is used to investigate patients with suspected bile acid malabsorption
Bile acid malabsorption
Bile acid malabsorption is a cause of chronic diarrhea. It can result from malabsorption secondary to gastro-intestinal disease or be a primary disorder. Treatment with bile acid sequestrants is often effective.-Classification:...

, who usually experience chronic diarrhea, often passing watery feces 5 to 10 times each day. When ileum has been removed following surgery, or is inflamed in Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

, the 7-day SeHCAT retention usually is abnormal, and most of these patients will benefit from treatment with bile acid sequestrants. The enterohepatic circulation
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....

 of bile acids is reduced in these patients with ileal abnormalities and, as the normal bile acid retention exceeds 95%, only a small degree of change is needed. Bile acid malabsorption
Bile acid malabsorption
Bile acid malabsorption is a cause of chronic diarrhea. It can result from malabsorption secondary to gastro-intestinal disease or be a primary disorder. Treatment with bile acid sequestrants is often effective.-Classification:...

 can also be secondary to cholecystectomy
Cholecystectomy
Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...

, vagotomy
Vagotomy
A vagotomy is a surgical procedure that involves resection of the vagus nerve.-Applications:Truncal vagotomy is a treatment option for chronic duodenal ulcers...

 and other disorders affecting intestinal motility or digestion such as radiation enteritis, celiac disease and small intestinal bacterial overgrowth.

A similar picture of chronic diarrhea, an abnormal SeHCAT retention and a response to bile acid sequestrants, in the absence of other disorders of the intestine, is characteristic of idiopathic bile acid malabsorption
Bile acid malabsorption
Bile acid malabsorption is a cause of chronic diarrhea. It can result from malabsorption secondary to gastro-intestinal disease or be a primary disorder. Treatment with bile acid sequestrants is often effective.-Classification:...

 – also called primary bile acid diarrhea. These patients are frequently misdiagnosed as having the irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...

, as clinicians fail to recognize the condition, do not think of performing a SeHCAT test, or do not have it available.

There have been at least 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...

 patients. When these data were combined, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant
Bile acid sequestrant
The bile acid sequestrants are a group of medications used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic...

.
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