Clinical Information

Bile acids are synthesized from cholesterol in the liver and released into the digestive tract where they function to emulsify dietary fats and facilitate lipid absorption in the small intestine. More than 95% of bile acids are then reabsorbed primarily by active uptake in the distal ileum, while less than 5% are excreted in stool. The synthesis of bile acids in the liver is regulated by a negative feedback mechanism from the bile acids reabsorbed from the intestine. 7 Alpha-hydroxy-4-cholesten-3-one (7aC4) is an intermediate in the biosynthesis pathway of cholesterol to bile acids. The concentration of 7aC4 in serum is a surrogate for the amount of bile acid synthesis in the liver. There is some diurnal variation in 7aC4 serum concentrations, so measurement should be performed on a fasting morning sample.

Patients with increased bile acid in their stool suffer from chronic diarrhea termed bile acid diarrhea (BAD). Approximately 10% to 33% of patients with irritable bowel syndrome with diarrhea have BAD. Additionally, BAD has been identified as a contributor of diarrhea in other conditions such as irritable bowel disease (IBD), Celiac disease, microscopic colitis, and neuroendocrine tumors.(1) Identifying patients with BAD can be done by measuring total and fractionated bile acids in stool. The increased bile acids in feces can be caused by an inability to reabsorb bile acids in the terminal ileum (bile acid malabsorption: BAM). If the intestinal reabsorption if BA is decreased, this leads to increase synthesis of bile acids in the liver. Recent studies have shown that serum concentrations of 7aC4 are elevated in patients with BAD. Several intestinal diseases or functional abnormalities can lead to BAD.

The definitive test in the United States for BAD is the 48-hour stool bile acids test (BA48F / Bile Acids, Bowel Dysfunction, 48 Hour, Feces). However, given the challenge of a 48-hour specimen collection, a random stool collection can be used in combination with the results from serum 7aC4 testing. From a random stool collection, only the percentage of primary bile acids can be reported. Internal studies have shown that a combination of serum 7aC4 result above 52.5 ng/mL and primary fecal bile acid result above 10% is 66% sensitive and 95% specific for BAD.(2)

Identification of these patients can influence treatment decisions that could include the use of bile acid sequestrants. Conversely, patients with irritable bowel syndrome with constipation may have lower circulating 7aC4 as compared to healthy individuals.